In This Issue
Wearable diagnostics are on trend
Another potential blood test for Alzheimer’s
Liquid biopsy trends
This week in AI
Yes, bad sleep does trigger migraines
New and Noteworthy
Long COVID protein signature provides hope for a test
It is not a clinical diagnostic yet, but researchers have found a protein signature predictive of persistent symptoms (fatigue and cognitive difficulties) long after recovering from acute COVID. The particular mixture of abnormalities - some protein levels are increased, others decreased - shows that the complement system and part of the blood clotting process is overactive in patients with Long COVID, especially those who are older or have higher BMI. (The C5bC6 / C7 complexes in the chart shown here are part of the complement system.)
The complement pathway is part of what is called the innate immune system, and part of its job is to help get rid of invading microbes and damaged cells. As we reported in September, a Nature paper convincingly demonstrated widespread immune-system dysfunction in patients with Long COVID (which occurs after 5% of all infections and up to 20% of severe cases). This research, published in Science, may indicate which parts of the immune system lie at the root of the problem.
Commentary: Specificity is a potential issue, because complement activation can be kicked off by any injury or current viral infection. The study is small, but tests based on the identified proteins could be the basis of accurate diagnostics.
Wearable diagnostic devices are hot, and not just for Apple
Last week Nature Biotechnology reported the development of a new device, UltraSound on a Patch. It is a battery-powered, wifi-connected, ultrasound device linked to a smartphone that can monitor heart activity in real time when patients are at rest or active.
Commentary: With its smartwatch, Apple has demonstrated just how capable small wearable devices can be at monitoring clinically relevant trends. The large end-user market for these devices is driving down the cost and dramatically reducing the size of ever-more-complex compact sensors.
There is lots to love here. But our questions are twofold:
Will consumers use the health-monitoring tools beyond the fun first week after purchase? Will they get over their privacy concerns?
If they do use these features, will doctors believe the data and act on it?
The search for a blood test for Alzheimer’s disease continues
A recent paper in JAMA Neurology evaluated a phosphorylated Tau blood test for Alzheimer’s disease (the specific biomarker is pTau217) and concluded that it was as good as existing imaging and cerebrospinal fluid tests for 80% of patients. It was also effective at tracking subsequent development after initial diagnosis.
Commentary: There have been and continue to be many alternative proposals for effective blood biomarkers (e.g. Aβ42/40, GFAP, NfL, other phosphorylated Tau proteins), but data here looks strong. FDA approval of the first effective Aβ-reducing drug (lecanemab/Leqembi®) fueled increasing demand for an inexpensive and non-invasive test. However, recent data questions lecanemab’s benefit versus its serious side effects: A recent metastudy concluded it to be inferior to placebo using the clinical dementia rating scale. Note: Mara was involved in the initial stages of the company announcing this newest blood-based test.
Liquid biopsy progress keeps on accelerating
Genome Web recently published a review of liquid biopsy progress in 2023 that is well worth reading. Some highlights:
Payors’ increased willingness to shell out for this kind of test not just for colorectal cancer (the only one that they used to approve) but for breast cancer as well
Use of liquid bx for colorectal cancer staging as well as initial Dx
Likely expansion of the field into tests for melanoma and bladder and lung cancer.
Commentary: The advantages of liquid biopsy in targeted cancer diagnosis and monitoring are enormous: It is effective (selectively), relatively inexpensive (versus imaging), minimally invasive, and reflects cancer independent of tissue location. As such it enables more frequent monitoring of at-risk individuals to detect cancer emergence or recurrence after successful treatment, and its clinical utility continues to evolve. Our own growing list of companies making strides in this area is above, and it is certainly incomplete.
This week in AI
Use of an AI algorithm that flags patients who may be about to develop sepsis was associated with a 17% relative decrease in sepsis mortality (1.9% absolute reduction) in a study of over 6,000 patients admitted to the emergency departments of UC San Diego Health. The tool is able to single these cases out before they show clear clinical signs by following more than 150 different variables that can be linked to sepsis.
Last week the WHO released updated guidelines for large multimodal models (LMMs) used for health purposes. These AI tools can learn from a variety of different types of input: For example, an LLM might understand not just text, but audio, video, and images, as well. The guidelines express concern about the fact that LLMs are being produced almost exclusively by tech companies (not universities or governments) in wealthy nations, and recommends independent, mandatory audits of large-scale LLMs after they are released. They also recommend that people who develop LLMs for health-care purposes receive ethics certification or training.
Use of an AI-enabled digital stethoscope allowed clinicians to detect peripartum cardiomyopathy at double the rate of standard care, according to findings presented at the American Heart Association’s Scientific Sessions 2023. The stethoscope analyzes both EKG readings and heart sounds to diagnose the condition, a weakening of the heart muscle in pregnant and recently pregnant women.
Food for Thought
You were right: Bad sleep does make a migraine more likely
Migraine is one of those conditions that lies dormant and then flares - early warning of those flares can allow treatment that may help prevent or at least lessen the pain (it doesn’t always work). A new study with almost 500 people showed that perceived sleep quality and lower-than-usual quality of sleep can be an early warning: It is associated with an increased risk of migraine the next morning.
Commentary: As Mara is a migraineur, she joins with others who understand the challenge here and is thrilled with any new data. That being said, most people with migraine know their own triggers - and sleep quality and quantity count as triggers for most people. So the benefit of this research is less about diagnosis and more about, as the researchers note, gaining “insight into the processes underlying migraine [that can] help us improve treatment and prevention.”
Quick Hits
Diagnostics don’t have to be high-tech to be effective. Case in point: A large study in JAMA Network Open showed that the self-reported ability to easily walk one kilometer was highly predictive of fracture risk over the next five years in adults older than 45.
The SARS-CoV-2 virus has been found lurking and mutating in yet another species. As researchers report in the February 2024 issue of Emerging Infectious Diseases, a version of the Delta variant with several novel mutations was found in beavers at a conservation facility in Ulaanbaatar, Mongolia.