Ahmad Masri Profile picture
Sep 4 16 tweets 7 min read
Dr. Merlini talks on AL amyloidosis as a model for treating other amyloid disorders
#ISA_2022
Light chains cardiotoxicity in many studies
The age dependent process of handling LC #ISA_2022
Tissue specific impairement
#ISA_2022
Imapirement of mitochondria plays a central role in failure of clearance of misfolded protein #ISA_2022
Age dependent LC toxicity in endothelial cells #ISA_2022
Mechanisms of increased NTproBNP /BNP increase #ISA_2022
NTproBNP as a biomarker in AL
#ISA_2022
The problematic issue of late diagnosis of AL amyloidosis #ISA_2022
AL is an a state at the intersection of MGUS and MM
#ISA_2022
Why we need fibril removers in advanced disease
#ISA_2022
CAEL 101 pIII is underway
#ISA_2022
Mice dont develop amyloidosis #ISA_2022
A trangenic mouse model was reported on #ISA_2022
The pipeline for fibril removers #ISA_2022
A model of cure
#ISA_2022

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More from @MasriAhmadMD

Sep 4
A different tale of making use of amyloids - the good side
#ISA_2022
Examples of good functional amyloids produced in nature #ISA_2022
A set of ways amyloids can be used by bacteria #ISA_2022
Read 7 tweets
Sep 4
The keynote address by Dr. Weyand discussing aging of the immune system #ISA_2022
The aging nation
Aging and diseases
Read 9 tweets
Dec 19, 2020
Preclinical and phase I data for $AKCA-TTR-LRx (second generation inotersen, ASO conjugated with GalNAc), currently being tested in CARDIO-TTRansform, the largest #ATTR #Amyloidosis trial to date. Tafamidis allowed without restrictions.

onlinelibrary.wiley.com/doi/epdf/10.10…

#cardiotwitter
Cojugation with GalNAc increased potency by 20-30x, allowing lower dose, lower frequency, less AE
Read 4 tweets
Jun 20, 2020
Thread/

There are many new exciting trials in transthyretin #amyloidosis – as we continue to enroll patients in the CARDIO-TTRansform trial, I thought I would highlight some of these trials in ATTR-CM

clinicaltrials.gov/ct2/show/NCT04…

#cardiotwitter Image
If you recall, 2 main approaches to treating ATTR #amyloidosis with approved drugs (figure credit @frederickruberg @maz_hanna )
1)Stabilizers: bind to the TTR tetramer to stabilize it. #tafamidis , AG-10, diflunisal
2)Silencers: Inotersen and Patisiran Image
tafamidis is prescribed to ATTR-CM pts & inotersen/patisiran for those with hATTR polyneuropathy
But – 2 main questions in ATTR-CM
1)Which is associated with better outcomes – silencer or stabilizer?
2)Is the combination of silencer+stabilizer superior to stabilizer only?
Read 13 tweets
Dec 23, 2018
A thread.
So the @US_FDA @SGottliebFDA issued a warning re: Fluoroquinolones (FLQ) and aortic dissection (AD) or aneurysm (AA). Do FLQs cause AD/AA? Not really. Is there an association? Maybe. Let’s go throw the evidence and you can decide for yourself.
#CardioTwitter #MedEd
1/ Why was this association even studied? FLQ are known to be associated with Achilles tendon rupture, tendinopathy, retinal detachment. How? 1)decrease collagen synthesis and increase MMP (especially 2, 9) activity (among others). Aorta is affected by these processes
2/First study was published in 2015 using a national database in Taiwan. 1477 cases (662 AD, 850 AA) matched to 147 700 controls. There was signal of the association of FLQ and AD; rate ratio ranging 1.37 - 2.11 with any FLQ use (tinyurl.com/ybhcpexz)
Read 13 tweets
Nov 29, 2018
A great case of bicuspid-associated aortopathy.
How common is aortic dissection in BAV? To date, many surgeons operate on patients with dilated aortas in the 4.5-5.0 cm range without concomitant severe valve disease. But, how about the evidence so far?
#cardiotwitter #MedEd
1) IRAD had 1.9% BAV patients in a 2006 report (out of 303 type A dissections)
ncbi.nlm.nih.gov/pubmed/16820599
2) GenTAC registry had 2 dissections / 772 BAV (follow-up 3.6 years, outcome ascertained in 88%)
ncbi.nlm.nih.gov/pubmed/27282895
Read 8 tweets

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