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Tony Breu Profile picture
@tony_breu
Sep 17, 2020 • 5 tweets • 3 min read • Read on X
1/4
 Why does amphotericin B lead to rigors and fever?

I learned about his side effect by the moniker "shake and bake" (thank you First Aid).

Let's have a brief look at this commonly tested side-effect.
2/
 Amphotericin B was introduced in the 1950s.

It was clear early on that fevers and chills were common side effects.

More contemporary data show lower - though still relevant - rates of both side effects.

pubmed.ncbi.nlm.nih.gov/13749466/ - 1960
pubmed.ncbi.nlm.nih.gov/10072411/ - 1999
3/
 When thinking back to the mechanism of fever, recall that PGE₂ is a key mediator.

Amphotericin B leads to an increase in PGE₂. This is likely the mechanism of chills and fever.

As this study shows, amphotericin B acts in a similar way to LPS!

pubmed.ncbi.nlm.nih.gov/3309074/
4/4
 Given these effects, amphotericin has been examined as an "immunostimulant" in combination with antineoplastic chemotherapy.

I am unaware of its use in any current regimen.

pubmed.ncbi.nlm.nih.gov/7362372/
This is my first follow-up to a tweetorial on fevers, chills, and rigors.

Next up: meperidine (Demerol)

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More from @tony_breu

Tony Breu Profile picture
Nov 16
1/14
🤔 Why do we use iodine as an intravenous contrast agent?

The answer requires a review of the composition of the human body and a brief tour of one of my favorites, the Periodic Table of Elements. Image
2/
 To begin, it's essential to understand which elements make up the human body. Amazingly, just six compose >98% of your weight:

➤Oxygen: 61% (varies based on water composition)
➤Carbon: 23%
➤Hydrogen 10%
➤Nitrogen: 2.6%
➤Calcium: 1.0%
➤Phosphorus: 0.6%

buff.ly/3YU4dIYImage
3/
 One thing you'll notice about these six elements is that they are relatively small (i.e., they have low atomic numbers, aka are low-Z elements).

In addition to being the most prevalent elements in the universe, their low atomic number allows them to more readily form stable chemical bonds.Image
Read 14 tweets
Tony Breu Profile picture
Jun 22
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…Image
3/7 - The Diagnosis II

Some have resorted to random skin biopsies to make the diagnosis of IVL.

And multiple case series have demonstrated that a diagnosis of IVL can be made this way, even when the skin appears normal.

pubmed.ncbi.nlm.nih.gov/18053461/Image
Read 7 tweets
Tony Breu Profile picture
Jun 20
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/
3/
 A 2022 study found a similar rate, with 13% of patients with HCC showing no evidence of cirrhosis.

When looking more specifically at hepatitis C (HCV) versus hepatitis B (HBV), they found varying rates:

➣ HCV: 6% of patients with HCC were non-cirrhotic
➣ HBV: 19% of patients with HCC were non-cirrhotic

pubmed.ncbi.nlm.nih.gov/34027591/Image
Read 11 tweets
Tony Breu Profile picture
Apr 9
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…Image
3/12 - An Initial Explanation (I)

The effect of SGLT2 inhibitors on HCT/HGB has been noted since the very first randomized control trial of dapagliflozin, published in 2010.

Initially, investigators assumed this was related to the diuretic effect of these drugs (i.e., a reduction in plasma volume led to an increase in HCT/HGB).

pubmed.ncbi.nlm.nih.gov/20609968/Image
Read 12 tweets
Tony Breu Profile picture
Feb 22
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/Image
Image
3/
 The mutation in the Factor V gene conferring resistance to activated protein C was detailed the following year by a group in Leiden, The Netherlands.

Thus the name for the condition: Factor V Leiden.

pubmed.ncbi.nlm.nih.gov/8164741/Image
Read 10 tweets
Tony Breu Profile picture
Feb 18
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/Image
3/
 Another study of 882 patients with vascular Behçet Syndrome reported the following rates of deep vein thrombosis (DVT) and pulmonary embolism (PE):

➣ DVT: 592/882 (67%)
➣ PE: 0%!

pubmed.ncbi.nlm.nih.gov/24907156/Image
Read 9 tweets

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