Nick Mark MD Profile picture
Dec 18, 2021 9 tweets 6 min read Read on X
Yesterday I gave grand rounds lecture at @NJHealth about the Omicron Variant: molecular biology, epidemiology, and clinical pearls.

Here's the video & link to download my slides.
🎥
📂 onepagericu.com/blog/grand-rou…
Google says AH-MUH-KRAN is 🇺🇸 & OH-MU-KRON is 🇬🇧
Oversimplified..

In ancient Greek, there were 2 letters pronounced similarly:
Ω made a long Oooo - it was called big O or O Mega
Ο made a short Oo - it was called little O or O Micron

Thus, OH-MI-KRON is probably more accurate
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To understand Omicron, we need to understand pandemic surveillance:

A sick person 🤒 gets COVID tested.
The (+) results get sequenced (depending on where in the 🌎 ) & published to @GISAID (or other platform).
Sequences are used by researchers globally, such as @nextstrain.
3/ Image
Using @nextstrain to analyze those surveillance sequences we can watch the evolution of Omicron unfold:

Note the appearance of variants, particularly Delta in Summer 2021.

Omicron appears in October/November 2021.

On November 26, the WHO declared it a variant of concern.
4/
Omicron has ~50 mutations (compared to the original strain) but >30 of them are in one gene: the Spike Protein

This is worrisome because the Spike (S) protein binds to ACE2. It's also what our immune system "sees" & makes Ab against

👀 at covariants.org for more
5/
🔬 Let's look under the hood at the Spike protein mutations:
~15 in the receptor binding domain --> these *might* cause immune evasion

H655Y, N679K, P681H --> furin cleavage site mutations likely ⬆️ transmission

Q498R & N501Y --> tighter ACE2 binding, likely ⬆️ transmission
6/
One mutation is actually useful:
The TaqPath test amplifies the S gene using PCR.

In omicron the S gene won't amplify because of deletion of 2 residues (H69-, V70-). We call the failure to amplify S Gene Target Failure (SGTF).

👉🏻You may see "SGTF" as a surrogate for Omicron
7/ ImageImageImage
Because sequences are available, the effect of the mutations can be studied in vitro & in silico

Redd et al found that despite the spike protein mutations virtually all T-cell epitopes were preserved, suggesting the virus hasn't evaded T cell immunity
biorxiv.org/content/10.110…
8/ Image
Another lab (Garcia-Beltran et al) found that pseudovirus particles made with the Omicron mutant spike protein were significantly more able to infect ACE2 expressing 293T cells

2x as infectious as the Delta spike and 4x the original
medrxiv.org/content/10.110…

That's worrisome..
9/ Image

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More from @nickmmark

Mar 9
Every year, there is a predictable spike in fatal car accidents, medical errors, & heart attacks.

It’s estimated that there are thousands of excess deaths, a 1% increase in energy consumption, & billions of dollars in lost GDP.

The cause? Daylight savings transitions.

🧵

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Earth's axis of rotation and orbital axis are not precisely aligned. The 23.5 degree difference - 'axis tilt' - gives us our seasons and a noticeable difference in day length over the course of the year.

2/
For millennia this seasonal variation was an accepted fact of life.

In 1895, George Hudson, a New Zealand entomologist, was annoyed that less afternoon light meant less time for bug collecting.

He realized that clocks could be adjusted seasonally to align with daylight.

3/ Image
Read 27 tweets
Feb 14
Musk is so stupid. Exhibit #10544

There aren’t thousands of 150 year olds getting paid social security. There are null values in a database he doesn’t understand how to read… Image
When unidentified people get admitted to the hospital the default DOB is 1/1/1900. The EHR shows their age as 125 yo.

But *almost* everyone is smart enough to understand this is just a result of missing data… Image
Nice summary here debunking Elon’s “duplicate SSNs” claim.

thedatageneralist.com/elon-musk-does…
Read 4 tweets
Feb 8
Important point re indirects:

Unlike other Trump moves, this is arguably GOOD news for researchers!

If the NIH budget is unchanged (a big if), this allocates more money to researchers; if you go from an indirect of 75% to 15% it means you can fund 3 grants instead of 2.
Some context:

Between 1947 and 1965, indirect rates ranged from 8% to 25% of total direct costs. In 1965, Congress removed most caps. Since then indirects have steadily risen.

2/
A lot of indirects go to thing like depreciation of facilities not paying salaries of support staff.

This accounting can be a little misleading.

If donors build a new $400m building, the institution can depreciate it & “lose” $20m/year over 20 years. Indirects pay this.

3/
Read 4 tweets
Jan 22
🚨Apparently all NIH Study Sections have been suspended indefinitely.

For those who don’t know, this means there won’t be any review of grants submitted to NIH

Depending on how long this goes on for, this could lead to an interruption in billions in research funding.
With a budget of ~$47.4B, the NIH is by far the biggest supporter of biomedical research worldwide.

Grants are reviewed periodically by committees of experts outside of the NIH.

When these study sections are cancelled, it prevents grants from being reviewed & funded.
Hopefully this interruption will be brief (days)

A longer interruption in study sections (months) will inevitably cause an interruption in grant funding. This means labs shutdown, researchers furloughed/fired, & clinical trials suspended. This will harm progress & patients!
Read 8 tweets
Oct 13, 2024
#HurricaneHelene damaged the factory responsible for manufacturing over 60% of all IV fluids used in the US, leading to a major national shortage.

As clinicians what can we do to about the #IVFluidShortage and how can we prevent this crisis from happening again?

A thread 🧵
1/ Image
There are many things we can do as clinicians to improve ICU care & reduce IVF use.

1️⃣Don't order Maintenance IV Fluid!
Almost no patient actually needs continuous IV fluids.
Most either need resuscitation (e.g. boluses) or can take fluid other ways (PO, feeding tube, TPN).
2/
Frequently if someone is NPO overnight for a procedure, MIVF are ordered.
This is wrong for two reasons.
We are all NPO while asleep & don't need salt water infusions!
We should be letting people drink clears up to TWO HOURS before surgery, per ASA.

3/ pubs.asahq.org/anesthesiology…Image
Read 16 tweets
Oct 1, 2024
New favorite physiology paper: Central Venous Pressure in Space.

So much space & cardio physiology to unpack here including:
- effects of posture, 3g shuttle launch, & microgravity on CVP
- change in the relationship between filling pressure (CVP) & LV size
- Guyton curves!
1/

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To measure CVP in space they needed two things:
📼 an instrument/recorder that could accurately measure pressure despite g-force, vibration, & changes in pressure. They built & tested one!
🧑‍🚀👩‍🚀👨‍🚀 an astronaut willing to fly into space with a central line! 3 volunteered!
2/
Image
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The night before launch they placed a 4Fr central line in the median cubital vein & advanced under fluoro.

🚀The astronauts wore the data recorder under their flight suit during launch.

🌍The collected data from launch up to 48 hrs in orbit.
3/
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Read 16 tweets

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