When testing is recommended, does it happen?
Volume 10, Issue 10 | September 12, 2024
In This Issue
Low-dose CT: Optimal for low-risk lung cancer?
Using transcriptomics to diagnose blood clots
When further testing is indicated, do those tests happen?:
A look at breast cancer and diabetes
The latest on bird flu
New and Noteworthy
Is transcriptomics a better way to identify blood clots?
Overactive platelets create life-threatening clots that can block the blood supply to limbs and organs. These clots can show up while you’re sitting on an airplane, after you have surgery, or for no obvious reason at all. So wouldn’t it be good to know if someone’s platelets are overactive?
Such a test has existed for a while - it’s called a platelet aggregation test - but it’s labor-intensive and requires a lot of expertise and quality control. In a recent study in Nature Communications, researchers investigated whether they could tell that someone’s platelets were overactive not by looking at the platelets themselves, but by looking at the person’s genetics or epigenetics instead.
They developed a 451-gene transcriptome panel called the Platelet Reactivity ExpreSsion Score (PRESS) for this purpose, and tested it in people at the highest risk of having a blood clot: folks who’ve had a clot before. Of 254 patients undergoing surgery to restore blood flow after a leg clot, 19% had another clot in the 30 days after their surgery. Those that PRESS identified as having overactive platelets were 3.2x more likely to have a heart attack and 4.9x more likely to require amputation.
Commentary: What about INR testing, which is used to titrate the dosage of blood thinners like warfarin – isn’t that test far cheaper and easier than something like PRESS? Well, yes and no.
On the yes side: It is hard to see how even next-generation sequencing could get clinicians to routinely run a 451-gene mRNA transcriptome panel.
But on the no side: Clotting can occur in a patient whose INR is within normal bounds. It is this platelet hyperactivity that the PRESS panel (and traditional platelet-aggregation tests) seek to quantify. Plus, we now know that platelets also have a role in broad infection response. It is clear that this is a field that warrants more attention.
Bird flu: Human case with no known animal contact, USG partners with commercial labs, wastewater reveals flu across TX
A person in Missouri who reported no contact with animals was hospitalized with H5 influenza in late August and has since recovered. The strain of virus in the patient’s sample was closely related to the one infecting dairy cattle, but because the sample did not contain much viral RNA, investigators may not be able to obtain a full genetic sequence. Public-health officials have not been able to find any people who caught the flu from the person in question, but investigations are ongoing.
The CDC has partnered with five commercial labs to scale up testing capacity for bird flu. The labs will be able to develop their own tests for the virus.
During weekly wastewater testing in 10 Texas cities from March through mid-July, H5N1 virus was found in all 10 cities and in 22 of 23 testing sites. Genomic testing and other indicators suggest that the virus came from multiple animal sources, including both birds and mammals.
Food for Thought
When disease or risk prompts further testing, do those tests happen?
Sometimes, getting a diagnosis reveals the need for further testing. Other times, just being at risk for one disease implies you’re also at risk for another and should get tested for it. So does this second round of testing happen? Turns out clinicians are better about it for some diseases than they are for others.
Most breast-cancer survivors get genetic testing, but not all - yet
Twenty-six million people in the US will be cancer survivors by 2040, according to a new study published in the Journal of the National Cancer Institute. Of this group, breast-cancer survivors make up the largest number: 4 million people. And of those who are eligible among that 4 million, 75% get genetic testing and related counseling, according to a new study published in the Journal of Clinical Oncology. Of folks who do get tested and find they have genetic variants, almost two-thirds share that information with family members. The study included 1,412 women who were surveyed in the first and sixth year post-diagnosis.
Commentary: All the headlines about this study focused on the negative, fretting about the 25% who don’t get genetic testing. While we agree that 100% would be better than 75%, 75% is still one heck of a lot better than 0%. The increase in cancer survivorship (fourfold since 1970) in conjunction with increased understanding of the genetics of cancer brings into focus the importance of genetic tests and related genetic counseling for the patient and family members. (Note - Mara is an Observer of a company that offers genetic counseling.)
Many Type 2 diabetics don’t get recommended kidney screening
Folks who have Type 2 diabetes are at risk for a range of health issues, one of which is kidney disease. Unfortunately, the majority of them don’t get screened for it. A large study of 300,000-plus people with Type 2 diabetes tracked over five years showed that only 25% received the two recommended tests to assess kidney function (creatinine and urinary albumin-to-creatinine ratio). A further 56% had one of the two tests, and the remaining 19% got no testing at all.
Mammograms are a good time to suggest other screening - and offer a kit
The anti-breast-cancer industrial complex has done a good job of getting the idea of annual mammograms into the heads of middle-aged women. But the girls aren’t the only body parts at risk in this cohort - cervical cancer (CC) and colorectal cancer (CRC) can hit us, too.
A large study (over 27K subjects) published in PLOS Medicine looked at women ages 50 to 64 who were getting mammograms, to see if an additional push at that appointment would increase screening for other diseases. It found that when women who were overdue for cervical cancer or colorectal cancer screening were offered self-collection kits, they were much more likely to get screened for the additional cancers within the next six months (26% more likely for cervical cancer, 15% more likely for colorectal).
Commentary: Was it the timing of the offer, the self-selected group of subjects (women who are already on board with doing one type of screening), or the self-collection kit that did it? Maybe it doesn’t matter - it’s a good paradigm that’s worth replicating.
Low-dose CT lung cancer screening follow-up:
For low-risk individuals, false positive rate is too high
If you’re a 50- to 80-year-old smoker with at least 20 pack-years of smoking history, you’re the definition of a person at high risk for lung cancer. If you’re a former smoker with at least 20 pack-years under your belt and you quit less than 15 years ago, you’re in the same boat. You should get screened for the disease, and a low-dose CT (ldCT) is a good screening tool for you.
However, fewer and fewer folks fit those criteria, because fewer people smoke these days. While that’s undoubtedly a good thing, we’re getting to a point where the majority of lung-cancer cases are arising in people who are, in smoking-based terms, at low risk. Should we be screening all those folks (we commented on this topic recently), and if so, how?
A reader of ours pointed us to an April 2024 Radiology paper that suggests we shouldn’t, at least not with ldCT. While lung nodules larger than 30 cubic millimeters were found in 48% of men and 38% of women in the study (of 10,431 low- to medium-risk northern European individuals), only 11% of subjects had nodules that were considered “clinically relevant” enough to require a repeat ldCT 12 months later. And only 2% of subjects had “clinically actionable” nodules: ones that were larger than 300 cubic millimeters. Those were the folks who went on to have a follow-up PET/CT and biopsy, and only 13% of them (0.3% of the overall group) were confirmed to have primary lung cancer.
Commentary: The bottom line of this study: If we use ldCT to screen lower-risk folks for lung cancer, overdiagnosis is unavoidable. This false-positive rate is just too high.