Tony Breu
@tony_breu · Boston, MA · joined 05 Apr 2012
Hospitalist, VA Boston. Assistant Professor, @harvardmed and @HMSbioethics. Co-host, @CuriousClinPod. Usually at #AMreport. Views are my own.
107 872Followers
894Following
9 133Posts total
528.4KViews on collected posts
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1/15
🤔Does end-stage renal disease (ESRD) make diabetes disappear?
No, but in some patients with ESRD, insulin needs fall. A1c drops. Diabetes medications can be stopped.
This has been called “burnt-out diabetes.”
Let's examine why.
23.1K views · 251 likes
· 91 reposts · 4 replies
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More evidence that kids are better at observation.
I'm walking out of my hospital today when my 8-year-old son asks, "Dad, why are the stairs so short?"
I've walked and "seen" the exact set of stairs thousands of times, but never made this observation. I was reminded of an http
6.7K views · 28 likes
· 0 reposts · 4 replies
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Can someone help me understand this forest plot? It's taken from a 2007 meta-analysis of antithrombotic therapy in atrial fibrillation.
How could the point estimate for the 7 aspirin-only trials favor placebo or control when all but 1 study favors aspirin?
I'll note that SPAF
5.7K views · 10 likes
· 3 reposts · 4 replies
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1/14
Why can't you use direct oral anticoagulants (DOACs) in patients with mechanical valves (MVs)?
DOACs have been one of the most important advances in my career. And yet, the presence of a MV is one of the few contraindications.
The reason highlights the unique nature of
135.4K views · 1.1K likes
· 359 reposts · 20 replies
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@tony_breu Fascinating! Lying in bed reading this by coincidence after mitral and tricuspid valve repair. Didn’t need a valve in the end but this thread answered some of the questions I didn’t want to waste my surgeons time with.
1.4K views · 4 likes
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18/18
➤ Before placement, bioprosthetic valve fixation with glutaraldehyde reduces antigenicity of the graft
➤ α-gal is not affected by glutaraldehyde; it therefore contributes to valve degeneration
➤ Valve tissue may have less α-gal leading to lessened risk of acute rejection
6.8K views · 51 likes
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17/
Before closing, one final connection.
There are emerging cases reports showing that those with α-gal allergy experience accelerated valve degeneration!
It isn't just about intolerance to red meat.
https://t.co/GObb2PyyOB https://t.co/zdhWWtBNCw
6.8K views · 25 likes
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16/
And given that bioprosthetic xenografts DO elicit an immune reaction that likely contributes to degeneration, some have wondered whether we ought to administer immunosuppression.
https://t.co/2nAlbdoYyt
4K views · 12 likes
· 2 reposts · 1 replies
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15/
This doesn't mean α-gal plays no role in rejection.
Some have suggested that it is a factor in the degeneration we have seen from the first valve replacements up through the present.
https://t.co/G2qQj8dsO9
4K views · 13 likes
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14/
This and a follow-up study showed that although porcine valve endothelium expresses α-gal, they do so much less intensely than aortic or vein endothelial cells.
Less α-gal may mean a lesser immune reaction.
https://t.co/ZvmWkB78Bn https://t.co/86vJAYGFYS
4.2K views · 14 likes
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13/
A clue comes from a 2000 study by Chen et al. They transplanted whole pig hearts into baboons.
Although the hearts were acutely rejected within hours after implantation...
...the aortic and pulmonary valves were entirely spared!
https://t.co/KWHiKUXuLT https://t.co/AjpwJM8
4.5K views · 12 likes
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12/
We therefore have two discordant findings:
☞ Glutaraldehyde (GA) does not eliminate the main antigen in acute rejection
☞ Patients receiving GA-fixed bioprosthetic xenografts don't experience acute rejection
How can we reconcile these two observations?
4.5K views · 23 likes
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11/
This was suggested by a 2011 study by Bloch et al.
It showed a sizable anti-α-gal antibody response even after glutaraldehyde (GA) treatment.
💡This indicates that GA treatment does not eliminate the immune response to the α-gal!
https://t.co/LUYLC0Zvel https://t.co/Ds7szd
4.9K views · 12 likes
· 2 reposts · 1 replies
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10/
But, glutaraldehyde cannot cross-link carbohydrates because of the absence of amino groups.
And, galactose-α-1,3-galactose is a carbohydrate!
This means glutaraldehyde does NOT mask α-gal and mitigate the immune response against this antigen.
5K views · 19 likes
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9/
After glutaraldehyde was added to the conditioning regimen, the rates of valve success at 1 year increased to 82%.
💡Glutaraldehyde is one reason we don't use immunosuppression after xenograft insertion: many antigens are masked by its cross-linking. https://t.co/Zql9vOKnDY
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8/
A solution was offered by glutaraldehyde (GA).
GA generates cross-links with amino groups of lysine or other amino acids resulting in "fixation" of the tissue.
This reduces the antigenicity of the valves.
https://t.co/ionGwpoO5p https://t.co/MQhcaPI0gH
5.4K views · 22 likes
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7/
Although early surgeries did not show hyperacute rejection they were accompanied by high rates of valve failure. At one year, just 45-50% were well functioning.
Explanded valves showed features indicating an immune response to the xenograft tissue.
https://t.co/ionGwpoO5p h
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6/
Despite the failures of prior xenotransplantation, on September 23, 1965, a team of French surgeons replaced the calcific aortic valve of a 48-year-old woman with a pig valve.
Immunosuppression was NOT used.
https://t.co/FLJ4TqIOmC https://t.co/Qp67YGNAZt
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5/
Two keys:
🔑 Most non-primates contain α-gal on organ epithelium
🔑 Humans lack α-gal
Result: α-gal is perceived as a foreign antigen by our immune system.
Would a reaction to α-gal lead to acute rejection of pig xenografts? This was a big question.
https://t.co/wq5Wjcvybm h
6.1K views · 15 likes
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4/
But, the history of xenotransplantation is riddled with failure, particularly when immunosuppression is not used.
💡The primary basis of hyperacute rejection to xenografts is the immune response to galactose-α-1,3-galactose (α-gal).
https://t.co/uoDhkXKQLn https://t.co/b4tcfi
6.7K views · 16 likes
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2/
First, some history.
The first valve replacements were performed in the 1950s and were made of plastic or metal.
The desire to forego anticoagulation saw the emergence of homografts (i.e., valves taken from human cadavers) in the 1960s.
https://t.co/JnEyJA0AyR https://t.co/
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3/
But, as with any human organ or tissue transplant, demand outstrips supply. This led to the emergence of heterografts (i.e., xenografts) in which a non-human valve is used.
Because pig hearts are similar in size and shape to humans, they were a natural "fit."
6.9K views · 13 likes
· 2 reposts · 1 replies
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1/18
🤔Why don't we use immunosuppression after bioprosthetic valve replacement?
Not only is the graft not self, but most aren't even from the same species and instead are from cows or pigs.
But unlike other transplants, we forego immunosuppression. Why?
Let's have a look. http
149.1K views · 436 likes
· 130 reposts · 12 replies
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Here is an updated list of my tweetorials.
https://t.co/EjeIgAvetn
113.4K views · 349 likes
· 104 reposts · 9 replies
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Against accounts of the same size
3 posts from the last 90 days, next to the 100K–1M follower range. shown widely, but few of those viewers react.
Median views6 716this account4 520median for 100K–1M
Reach, %6.23%this account1.64%median for 100K–1M
Engagement, %0.48%this account1.27%median for 100K–1M
| Metric | This account | Median for 100K–1M | Ratio |
|---|---|---|---|
| Median views per post | 6 716 | 4 520 | 1.49× |
| Reach (views ÷ followers) | 6.23% | 1.64% | 3.80× |
| Engagement rate | 0.48% | 1.27% | 0.38× |
Others in this range → Compare with another account → How these benchmarks are built →
Growth & engagement
How the posts we collected actually performed: views and reaction rate post by post, what the audience did with them, and where the follower count goes.
Views per post
5K28 Aug
4.9K
4.5K
4.5K
4.2K
4K
4K
6.8K
6.8K
1.4K
135.4K13 May
5.7K18 Jun
6.7K20 Jun
23.1K26 Aug
Last 14 collected posts, oldest on the left. The scale is logarithmic: one post can outrun the rest a hundred times over.
Engagement rate per post
0.44%28 Aug
0.31%
0.62%
0.33%
0.40%
0.40%
0.37%
0.41%
0.88%
0.35%
1.11%13 May
0.30%18 Jun
0.48%20 Jun
1.51%26 Aug
Reactions — likes, reposts, replies and quotes — divided by views. Median for 100K–1M accounts is 1.27%.
What the audience does
Likes48.5%2 510 in total
Reposts14.2%733 in total
Replies1.4%73 in total
Quotes0.9%49 in total
Bookmarks34.9%1 806 in total
Share of every reaction we collected for this account. Replies mean argument, reposts mean endorsement, bookmarks mean the post was worth keeping.
The follower curve appears once this account has two daily snapshots — we take one a day, and this one is on its first.
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