physician-scientist, author of SUPER AGERS https://xitter.twitterapi.xyz/t.co/ZEdooyyJpP and Ground Truths: https://xitter.twitterapi.xyz/t.co/YhatcBT0hA
La Jolla, CA
Joined November 2009
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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…
Moving on to preventing cancer with vaccines
With today's @NEJM publication of the melanoma treatment vaccine success nejm.org/doi/full/10.1056/NE…
The editorial notes the remarkable potential for vaccines to prevent cancer:
nejm.org/doi/full/10.1056/NE…
"a vaccine against 25 recurrent mutational hotspots
in genes such as KRAS, BRAF, and PIK3CA could
target mutations found in more than 70% of
colorectal, pancreatic, uterine, and melanoma
skin cancers."
And @moderna_tx declares it's the future with an ongoing trial to prevent Lynch syndrome and more to come
ft.com/content/30b27a58-35bf…,
Getting it wrong for many decades.
Since the 1950's, pacemaker leads have been placed in the right ventricle. A new randomized trial challenging that dogma found marked superiority of outcomes for pacing from the left bundle branch. nejm.org/doi/full/10.1056/NE…
A study on accelerated aging with chemotherapy for breast cancer
More aggressive chemo, improved breast cancer survival but a tradeoff of accelerated biological aging and increased risk of non-breast cancer mortality
jamanetwork.com/journals/jam…
The obesity adverse outcome story.
BMI is a poor and misleading way to quantify obesity
When the CAD-obesity definition is used, we see the increased risk of all-cause mortality (top graphs) and lesser risk for preclinical obesity (lower graphs)
@Nature
nature.com/articles/s41586-0…
The critical role the blood brain barrier (BBB) plays in the Alzheimer's disease model, and how to modulate the BBB "transportome" and rescue brain astrocytes @CellCellPress
cell.com/cell/fulltext/S0092…
"Simply Aging"
A brilliant perspective on the complex (anything but simple) biology of human aging, by @VadimGladyshev @gladyshev_lab open-access @PNASNews pnas.org/doi/10.1073/pnas.26…
Setting an unattainable objective. I wish it would come true, but curing all these diseases in the next 10 years is impossible.
And I'm very optimistic about the impact of AI for improving health.
The impressive impact of strength training for preserving muscle mass while taking a GLP-1 drug for obesity, as seen in randomized trial @NatureMedicine
T=tirzepatide alone (Zepbound), T + REx=drug with resistance exercise
nature.com/articles/s41591-0…
It's hard to beat @emollick for an up-to-date, independent assessment of AI, no less where we're headed. His new book is CO-EXISTENCE. We discussed that and a lot more in the new Ground Truths today
AI could reboot how science is done
Check out @emollick's energy!
erictopol.substack.com/p/eth…
Two of the most important opportunities for medical AI:
1. Give the gift of time to clinicians, to promote the patient-doctor relationship
2. Improve accuracy of diagnosis and treatments
Both are helped by this type of work
Excited for the launch of Gemini for Healthcare!
We’re extending the Gemini agent with specialized healthcare skills and connectors to Epic, Optum, and more, built to support HIPAA compliance.
Instead of spending hours piecing together fragmented records and policies, care teams can offload the admin burden and get time back for what matters most: patient care.
What accounts for genetic resistance to Alzheimer's disease and dementia?
Many known protective gene variants are very instructive
Feature @Nature
nature.com/articles/d41586-0…
The risk of blindness associated with GLP-1 drugs is ~2/100,000 people taking these drugs and properly noted by @FDA, the very rare condition known as NAION
wsj.com/health/pharma/u-s-re… by @AlexLJanin
Notable: Researchers from 50 institutions collaborate to find a biomarker that has the potential to detect ovarian cancer very early, even pre-malignant
A cancer not detected by the Galleri test.
An extracellular vesicle long non-coding RNA
@NatureMedicine
nature.com/articles/s41591-0…
nature.com/articles/s41591-0…
Semaglutide (Ozempic) improved left atrial and diastolic function in a randomized trial of patients with preserved ejection fraction heart failure (HFpEF) and obesity (via MRI)
And achieved remission of symptoms in more than half of participants (2nd link)
#AHA26 and @NatureMedicine
nature.com/articles/s41591-0…
nature.com/articles/s41591-0…
Two new randomized trials of the potent GLP-1 drug retatrutide (aka "reta") showed marked relief of knee osteoarthritis. Prior work demonstrated that some of the GLP-1 benefit for knee osteoarthritis is independent of weight loss.
#AHA26 @NEJM
nejm.org/doi/full/10.1056/NE…
Mechanistic work that shows the weight loss independent effect sciencedirect.com/science/ar…
Join @JoChikweMD, renowned cardiac surgeon, Chair of the AHA Scientific Sessions, Editor-in-Chief of the Annals of Thoracic Surgery, and me for a live audience, interactive Ground Truths at the 99th session of the American Heart Association today 11:30 CT (9:30 AM PT). On your phone, Substack app.
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…
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…
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.