.@DeptVetAffairs

Neko Health is as good as advertised. I got to be the 4th person to preview the new NYC location yesterday. The whole experience, from the moment you enter and head down the stairs, was dialed in. It felt like the future. Beautiful combo of design, technology, and people. Got a bunch of scans, bloodwork, and blood pressure done in ~30 minutes and as soon as it was done, they took me into a room to explain the results, which were all ready that quickly because there’s a lab on site (I won’t spoil how the blood gets there, maybe the coolest part). Luckily, I’m basically healthy but need to get my fat ass in shape. It’s wild that it costs $499, and they’re going to keep squeezing more tests into that price. They were nice enough to give me this one on the house but I already paid for my next appointment in 12 months. 10/10 would recommend.

The pattern is this. The assessment ruled heart failure unlikely because the NT-proBNP was low. The patient was obese, which lowers that number, and the JVP was elevated. The JVP was nowhere in the chart, so the model read missing documentation as a normal exam. Not a hallucination. Every fact it used was in the chart. The error was the inference from silence, which is why a stronger model reading the same chart makes the same call.

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Hormone tracking for women with a smart earring! Sounds fantastic, but the story of Phira also shows what's problematic these days with new companies developing wearables. I scanned through both their pages on the website; one is about how the device works and the other is the science behind it. I couldn't find the technological explanation I was looking for. The first page is about what they expect to add to women's health and the science page is more about the science behind the reason for tracking hormone levels. The only paper is a presentation they gave at an IEEE event. The clinical pilot study they mentioned has no citation, so we cannot look up its data. I'm sure they know what they are doing and maybe this whole secrecy is around protecting their IP and patents, but the medical community operates on the concept of evidence-based medicine. If you can prove that your technology works in studies, I'll be your biggest supporter. Until then, I always have Theranos PTSD no matter the company or the technology.

Hi all, The Lp(a) HORIZON trial has released topline data and, quite shockingly, missed its primary endpoint. In other words, lowering Lp(a) in patients with prior MI, stroke or peripheral arterial disease, who were otherwise very well treated for LDL-C, blood pressure, diabetes and other risk factors, did not reduce the primary cardiovascular endpoint. We obviously need to see the full data before making firm conclusions, and I don’t want to speculate too much without the details. But this is a big enough result that it is worth summarizing what we know, what we don’t know, and what this may mean for our patients after 20+ years of trying to test the “Lp(a) hypothesis.” What we know: 1-There are hundreds if not thousands of genetic, epidemiologic and Mendelian-randomization studies showing that elevated Lp(a) is associated with MI, stroke, peripheral arterial disease and aortic stenosis. That body of evidence is very strong. 2-However, much of those data come from community-based populations, often before the era of intensive LDL-C lowering and modern secondary prevention. 3-There has been much less information about how much residual risk Lp(a) carries in someone who has already had an event and is then treated very aggressively. 4-HORIZON may have had some of the best-treated patients of any recent cardiovascular outcomes trial. Baseline LDL-C was about 65 mg/dL, a measured LDL-C contains the cholesterol carried on Lp(a), so in reality, 15-20 points lower. 5-In patients with very high Lp(a), if you correct LDL-C for Lp(a)-cholesterol, the actual LDL-C carried by LDL particles may have been closer to 45–50 mg/dL, perhaps even lower in some patients. 6-This raises a very basic question: Can you still demonstrate a major incremental benefit from lowering another apoB-containing particle when the underlying LDL burden has already been driven this low? What we don’t know: 1-What was the actual corrected LDL-C in these patients? I think it would be extremely informative to directly measure Lp(a)-C and calculate corrected LDL-C. This may tell us a lot about the biological setting in which pelacarsen was being tested. 2- What was the OxPL status? Our prior work has suggested that much of the pro-inflammatory biology associated with Lp(a) is related to its enrichment in oxidized phospholipids. Did OxPL fall? Did patients with higher OxPL derive more benefit? Was Lp(a) concentration actually identifying the patients with the most pathogenic particles? 3- Did we measure the right component of Lp(a) for trial inclusion? We generally measure molar particle concentration. But is molar concentration itself the main driver of risk, or is it partly a surrogate for what the particle carries? Cholesterol? Triglycerides? Oxidized phospholipids? Other proteins? Could two patients with the same Lp(a) concentration have very different Lp(a)-mediated risk? I think this question deserves much more attention. 3- Were the genetic data telling us exactly what we thought they were telling us? The genetic data are extremely compelling, but genetics reflect lifelong exposure. A clinical trial treats patients late in life, often after decades of arterial injury and after an event has already occurred. Those are not necessarily the same experiment. Could there also be some unrecognized biology linked to the LPA locus that we have not completely accounted for? That possibility should at least be considered. 3- Does very low LDL-C modify the Lp(a) risk relationship? Maybe Lp(a) is particularly important when LDL-C is higher, but its contribution becomes smaller once LDL-C is driven to very low levels. Again, we need the data. 4- Does aspirin or other antiplatelet therapy reduce part of the risk associated with Lp(a)? Lp(a) has potentially important prothrombotic effects. Almost everyone in a trial like HORIZON is receiving contemporary antiplatelet therapy. Could that blunt one component of the risk associated with Lp(a)? 5- Why are these patients still having events? This may be one of the most interesting questions of all. These are patients with LDL-C around 65 mg/dL, and perhaps corrected LDL-C substantially lower, yet cardiovascular events continue to occur. What is driving that residual risk? Inflammation? Thrombosis? Plaque burden that is already too advanced? Other lipoprotein characteristics? Something we are not measuring? 6- Do we need to re-examine some basic assumptions about atherosclerosis? We have spent decades focusing heavily on the quantity of circulating lipoproteins. But perhaps lipoproteins are relatively benign until they undergo biological modification in the artery wall. Oxidation may be one of those key modifications. For some patients, the answer may be to remove more particles from the circulation. For others, perhaps the better approach is to prevent their oxidation or block the downstream biological effects of oxidized lipids. The recent difficulties with anti-inflammatory approaches, including IL-6 inhibition, make these mechanistic questions even more interesting. 7- Was there something specific about pelacarsen, the degree or timing of Lp(a) lowering, advanced disease, trial duration, background therapy or patient selection that mitigated a potential benefit? We simply don’t know yet. That is why the detailed results will be so important. What does this mean for patients today? If you have already had an MI, stroke or PAD, the immediate lesson is very clear: 1- Get all of your established risk factors treated aggressively. 2- Get LDL-C/apoB very low. 3- Control blood pressure. 4- Control diabetes. 5- Don’t smoke. 6- Use appropriate antiplatelet and other guideline-directed therapies. HORIZON shows us what modern secondary prevention should look like. If you have elevated Lp(a) but have never had an event, the genetic and epidemiologic data still suggest increased lifetime risk. Until the other 4 outcome trials read out, I would continue to treat every modifiable risk factor aggressively. We should wait for those trials before drawing broad conclusions about the entire field. I think the story of Lp(a) therapy is beginning, not ending. We also need to show tremendous respect and gratitude to the patients who participated in HORIZON and to the investigators and companies that invested enormous resources to actually test the Lp(a) hypothesis, to the ultimate benefit to peole with elevated Lp(a) to best guide how to manage risk. More to come as we go forward.

It's good that the benchmark scores are increasing, but if we've learned anything from GPT-5 versus GPT4o is that despite GPT-5 improving by 80-110% on these benchmarks compared to GPT4o, they still performed equivalently in some clinical evaluations. Benchmarks ≠ Clinical Performance

If you take a GLP-1 drug (Ozempic) late in life does it extend lifespan, slow aging, and improve physiologic function? Yes, if you're a female mouse New @Nature nature.com/articles/s41586-0…