1/7 - The Mystery

A patient presents with fever and confusion. After multiple weeks without a diagnosis, an astute clinician suggests a random skin biopsy.

The patient has no rash or dermatologic symptoms. And yet, the biopsy reveals the diagnosis.

🤔What is the condition? 2/7 - The Diagnosis I

💥Intravascular Lymphoma (IVL)💥

IVL can be an elusive diagnosis, given that many patients present without lymphadenopathy.

Instead, non-specific symptoms (e.g., fever, fatigue, weight loss, confusion) are more common.

ncbi.nlm.nih.gov/pmc/articles/P…

1/11
🤔Why does chronic hepatitis C infection "require" the intermediary of cirrhosis in order to cause hepatocellular carcinoma (HCC)?

Chronic hepatitis B can "skip" this step, going directly from chronic infection to HCC.

Why the difference? 2/
To begin, let's look at how frequently HCC occurs in patients without cirrhosis.

A 2019 study of United States (US) medical centers included 5144 patients with HCC.

💡12% had no underlying cirrhosis

pubmed.ncbi.nlm.nih.gov/31475372/

1/12 - Mystery #1

You are seeing a patient recently diagnosed with heart failure and started on GDMT. You notice that their hemoglobin (HGB) has increased (12 → 13 g/dL) in the intervening weeks.

🤔Which medication is the likely cause of this increase in HGB? 2/12 - An Answer

Empagliflozin

💡All SGLT2 inhibitors have been associated with an increase in hematocrit/hemoglobin soon after initiation.

The average increase is 2.3% in hematocrit and 0.6 g/dL in hemoglobin.

ncbi.nlm.nih.gov/pmc/articles/P…

1/10
🤔Why is pulmonary embolism (PE) relatively rare in those with Factor V Leiden?

This Factor V Leiden Paradox was pointed out to me by @DrSamelsonJones after I posted about a similar difference with Behçet Syndrome.

Let's have a look. 2/
In 1993, Dahlback, Carlsson, and Svensson first described a heritable resistance to activated protein C.

A year later the same group found this to be the most common form of hereditary hypercoagulability.


ncbi.nlm.nih.gov/pmc/articles/P…
pubmed.ncbi.nlm.nih.gov/8302317/

1/8
🤔Why is pulmonary embolism (PE) so rare in Behçet Syndrome?

The condition is associated with a 14-fold increased risk of deep vein thrombosis (DVT) but almost none of these result in PE.

What is it about the thrombus in Behçet that makes it so unable to embolize? 2/
Numerous case series have reported a markedly increased risk of deep vein thrombosis with Behçet Syndrome.

One reported the following rates of venous thrombosis:
➣ Behçet Syndrome: 18/73 (25%)
➣ Controls: 4/146 (3%)

pubmed.ncbi.nlm.nih.gov/11426022/

1/7
🤔What is the hemodynamic response to a chronic hemoglobin of 1.5 g/dL.

A fascinating 1963 study published in @CircAHA provides some interesting answers. Let's have a look at Patient One.

ahajournals.org/doi/pdf/10.116…
@CircAHA 2/
Patient One had chronic anemia with a hemoglobin 1.5 g/dL. You'll see that before receiving blood they had the following cardiac parameter:

• HR 100 (elevated)
• Cardiac index 8.9 (elevated)
• Stroke index 89 (elevated)

1/17
🤔Why don't we transfuse to a normal hemoglobin?

In many cases, we aim to restore values to the normal range. Potassium and other electrolytes. Even white blood cells.

But not hemoglobin.

In most situations, we accept >7g/dL, far less than normal. Why are we so tolerant? 2/
The principal rationale for red blood cell transfusion is to increase the O₂-carrying capacity and therefore O₂ delivery to tissues.

As hemoglobin is lowered O₂ delivery decreases, assuming all else remains unchanged.

So giving blood makes sense.

1/7 - The Mystery

A 57-year-old presents with the following labs:

WBC 2.7 / HGB 2.2 / PLT 111
Bili 3.2 (direct 0.4)
LDH 4360
Haptoglobin <10
INR 1.6 / PTT 35
Reticulocyte count 3.4
Smear with schistocytes

🤔What is the most likely diagnosis? 2/7 - The Answer

💡This patient was diagnosed with profound B12 deficiency secondary to pernicious anemia (PA)!

1/14
In a recent thread I discussed immunosuppression after xenograft heart valve replacement.

Did you know that we also use homografts (i.e., valves taken from human cadavers)? I didn't.

And these valves don't require HLA and ABO matching or immunosuppression either.

Why? 2/
Valve replacement surgery emerged in the 1950s to mitigate the dreadful outcomes of progressive heart valve failure.

The first valve was plastic and was placed in the descending aorta of a 30-year-old woman with rheumatic heart disease.

pubmed.ncbi.nlm.nih.gov/24539965/

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. 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.

dx.doi.org/10.4414/cvm.20…

1/13
🤔Why does iron administration relieve symptoms of restless leg syndrome (RLS) in some patients?

Turns out BRAIN iron deficiency matters more.

Let's have a look. 2/
In 1945 Karl-Axel Ekbom offered the first description of RLS.

Soon after Nils Nordlander observed that blood transfusion treated the condition. He then administered IV iron to 21 patients.

💡20 (95%) saw the complete resolution of symptoms!

https://t.co/X22mRa1srfpubmed.ncbi.nlm.nih.gov/13079659/

1/6
🤔Why does alcohol burn?

Placed on a wound or downed in a shot, alcohol leads to a noxious sensation on my skin or in my esophagus.

Sometimes it feels good, other times, not so much.

Let's have a look. 2/
The noxious burning sensation results from the activation of the capsaicin receptor.

Identified in 1997 and named vanilloid receptor subtype 1 (VR1), it is activated by:
🌶️ Capsaicin in hot and spicy foods
🌡️ Temperatures above 40-42ºC (104-107.6ºF)

pubmed.ncbi.nlm.nih.gov/9349813/

1/15
🤔Why does drinking alcohol make me feel warm?

I was recently at a soccer game with colder weather than anticipated. I told my friend I wish I had a flask with whisky to "warm me up." I soon realized, I didn't know how it had this effect.

Let's have a look. 2/
For centuries we've known that alcohol leads to a sensation of warmth.

In 1915 BMJ published letters on the military Rum Ration. Much of the debate related to this effect with Woodman arguing that coffee is hardly a practical substitute for alcohol.

bmj.com/content/1/2827…

I argue against sodium restriction in acute heart failure. The line of reasoning is that:

(1) Current evidence suggests restriction is not helpful.
(2) And may be harmful.
(3) There is a solid pathophysiologic basis for this evidence

https://twitter.com/guipenteadoo/status/1653764092253839362

Regarding evidence, the trials are small but generally consistent.

In 2013 Aliti showed no differences in change in weight or clinical congestion when a 800 mg/d sodium diet was compared with no restriction.

More thirst was seen in the restriction arm.

pubmed.ncbi.nlm.nih.gov/23689381/

1/18
🤔Why is the BUN/Cr elevated in upper gastrointestinal bleeding?

This question has been covered by @AdamRodmanMD and @WilliamAird4 but the literature is SO FASCINATING that I had to review it myself. @AdamRodmanMD @WilliamAird4 2/
In 1933 LV Sanguinetti reported the association between GI bleeding and elevated BUN.

The next two decades were the golden age of experimentation on this question with dozens of studies performed with the goal of identifying the cause.

dx.doi.org/10.1001/archsu…

1/12
🤔Why is plasma albumin low in nephrotic syndrome?

"Urinary losses!" seems like the obvious answer.

But there is much more to it.

Let's have a look. 2/
Recall that excretion of >3.5 g/day of protein is required for a diagnosis of nephrotic syndrome (NS).

In one study of 982 patients, the median value for proteinuria in NS was 6.7 g/day.

Can the liver make up for this daily loss?

pubmed.ncbi.nlm.nih.gov/28425160/

1/15
🤔Why does ticagrelor cause dyspnea?

In one analysis, dyspnea was the number one reason for drug discontinuation, accounting for 56% of withdrawals!

Let's have a look at this unexpected side effect of an anti-platelet agent.

pubmed.ncbi.nlm.nih.gov/24612612/
2/
The association between ticagrelor and dyspnea has been observed since the initial phase 2 trials.

Recent meta-analyses show significantly higher rates when compared with the more common P2Y₁₂ inhibitor, clopidogrel.

☞ OR = 1.9

ncbi.nlm.nih.gov/pmc/articles/P…

1/8 - The Mystery

It's 1981, 10 years before filgrastim is approved by the FDA.

You're hoping to mitigate chemotherapy-induced neutropenia in one of your patients.

🤔What medication might provide this ELEMENT of cancer care? 2/8 - The Answer

LITHIUM!

💡Soon after its use for bipolar emerged, LEUKOCYTOSIS was observed to be a common side effect.

pubmed.ncbi.nlm.nih.gov/20034171/

1/13
🤔Why does smoking cause leukocytosis?

I see this with some frequency but haven't taken to time to understand the mechanism.

Let's have a look. 2/
The association between smoking and increased white blood cell (WBC) count was first noted in 1970. The following counts were observed:

➣Never smoker: 5.8 × 10⁹/L
➣Quit: 6.0
➣Current (<20 cigarettes/day): 7.1
➣Current (≥20 cigarettes/day): 7.6

pubmed.ncbi.nlm.nih.gov/4194535/

1/16
🤔Why does carcinoid syndrome affect the right heart valves more often than the left heart valves?

The difference is striking.

Let's have a look. 2/
Let's start by confirming that the valves of the right heart are disproportionately affected.

A 1993 study of 74 patients with carcinoid heart disease reported the following rates by valve:

➤97% tricuspid
➤88% pulmonic
➤7% mitral
➤3% aortic

pubmed.ncbi.nlm.nih.gov/7681733/

1/6 - The Mystery

🤔Why do we use thrombopoietin (TPO) receptor agonists in immune thrombocytopenia (ITP)?

If the issue is peripheral destruction of platelets, why would ramping up TPO help?

Turns out, ITP Is more than a disease of platelet destruction! 2/6 - The Solution

In ITP, platelet destruction is central. But...

💡Depressed platelet production plays a role as well!

pubmed.ncbi.nlm.nih.gov/31483965/