Eric Topol

A new cover for SUPER AGERS after making the NYT bestseller list. Thanks to you for making it the #1 ranked new non-fiction book on Amazon. amazon.com/gp/new-releases/b…

Hypothesis testing :-)

Is this a potential future strategy for primary prevention of atherosclerosis? CRISPR base editing in vivo of the ANGPLT3 gene to achieve marked and durable lipid lowering. Promising data in experimental models, including hon-human primates, moving on to clinical trials @Nature nature.com/articles/s41586-0…

Why? I wrote about this when the initial results were released erictopol.substack.com/p/the… 1. Blood markers do not correlate with coronary inflammation which can be quantified now with AI. The drugs assessed need to demonstrate they markedly reduce coronary inflammation, ideally before investing hundreds of millions of dollars in large clinical trials. 2. The genetic, basic science and observational studies all support the potential interventions, but that doesn't translate to initiating them in the 7th decade of life with multiple co-morbidities for secondary prevention. 3. There are more potent, durable Lp(a) blockers in large trials, one of which is in high-risk primary prevention, a far more likely cohort to derive benefit. But that will not be read out until 2031! 4. Inflammation of coronary arteries as a driver of events and drug interventions to reduce inflammation to improve outcomes have been proven, but not commonly used (i.e.. colchicine) . We will eventually see other interventions validated, including at least one of those published on today, and move the field forward.

Today #AHA26 and @NEJM the 2 big trials of secondary prevention of heart disease with an IL-6 antibody and Lp(a) antisense oligonucleotide. No beneficial effect, overall and across all subgroups nejm.org/doi/full/10.1056/NE… nejm.org/doi/full/10.1056/NE…

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The cover to go with it

We are at the beginning of a new and exciting era to be able to program our immune system in the body (in vivo). This new review @SciImmunology nails it science.org/doi/10.1126/scii…

Predicting autoimmune diseases. The diagnosis of these diseases are often delayed by years. A randomized assessment of a predictive algorithm shows that can be avoided. @NEJM_AI ai.nejm.org/doi/full/10.1056…

A new study on brain health and estrogen: "Greater lifetime estrogen exposure, both endogenous and exogenous, was associated with lower cerebro-vascular pathology in women and, among APOE-e4 carriers, greater cortical thickness in AD-vulnerable regions." neurology.org/doi/pdf/10.121…

Epigenetic aging of kids and adults was accelerated during the Covid pandemic From a prospective longitudinal study pnas.org/doi/epdf/10.1073/pn…

It's one thing for AI models to ingest your written work without permission. Another is when this is done with your brain waves. @ScienceMagazine, by @jonathan_moens science.org/content/article/…

4. GLP-1 family of drugs and effects on cognition science.org/doi/10.1126/scie…

3. Why and how fat tissue adapts and remodels; interactions with lifestyle factors, health and disease science.org/doi/10.1126/scie…

2. Summary of GLP-1 drugs and their potential role for addiction therapy science.org/doi/10.1126/scie…