1/
First of 2 tweets! #GalactoMagic

60M presents w/ 7 days of fevers & SOB. T 38.1C, HR 105, BP 110/70, RR 22, O2 95% on 6L & then intubated. Exam notable for diffuse crackles. CT chest shows GGO bilaterally. He has a +SARSCoV2 NAT resp swab; sputum & blood cultures are negative
2/
After remdesivir, dexamethasone, ceftriaxone & doxy, he defervesces. 3 weeks later, he has worsening SOB. Repeat CT chest shows RUL cavitation. Serum BDG is 75 (positive>80) & serum GM is 0.4 (positive>0.5)

Which of the following diagnostics would have the highest yield?
1/13
Answer: BAL fluid culture

This patient is suffering from severe COVID-19 and is at risk for both bacterial and fungal super-infections

Although the most feasible test would be a sputum culture, the highest yield test for both bacteria and fungi is the BAL fluid culture
2/
There are many causes of cavitary lung lesions

For this tweetorial, we will focus on a fungal super-infection after COVID-19, specifically, COVID-19-associated pulmonary aspergillosis (CAPA)
3/
CAPA pathophysiology is not completely understood, but may be 2/2:
🐶Viral effect on ciliary clearance
🐱Direct damage to airway epithelium
🐭Lymphopenia
🐹Viral effects on cellular-mediated immunity-?local and systemic immune paralysis
🐰Steroid use

pubmed.ncbi.nlm.nih.gov/33050499/ Image
4/
CAPA incidence ranges from 4-35%

This range is likely due to:
⚽️difficulty in diagnosis
🏀geographic & center differences
⚾️differences in CAPA definitions
🥎limited use & sensitivity of serum fungal markers
🎾varying rates of bronchoscopy

pubmed.ncbi.nlm.nih.gov/32887998/
5/
CAPA is a disease entity seen in critically ill patients in the ICU

In addition to the reasons in tweet #4, CAPA can be difficult to diagnose because:
- it's hard to differentiate b/w colonization vs true pathogen
6/
As we discussed before, distinguishing b/w infection and colonization requires consideration of:
🍏host vulnerability
🍎clinical signs & symptoms
🍐results of non-culture techniques (BDG, GM)
🍊radiographic findings
7/
Since RECOVERY, we've been using steroids in patients w/ COVID-19

It's unclear whether SARSCoV2 is the main RF for CAPA, or it’s a combination of factors including steroids & now tocilizumab

Steroids may be a RF for CAPA by blunting macrophage activity➡️fungal germination Image
8/
In neutropenic & steroid-treated mice models...steroid-associated aspergillosis had necrosis, less angioinvasion, & lower fungal burden

If this process is seen in CAPA, the lower fungal burden can affect our ability to detect fungus & GM

pubmed.ncbi.nlm.nih.gov/18654923/ Image
9/
We know that CAPA is an entity in pts that are critically ill in ICU. It’s diagnosed when:
🐺respiratory status worsens despite ARDS mgmt & ruling out other causes
🦝new, persistent, or rising fever while ruling out other causes
🦊progressive infiltrates, nodules/cavitation
10/
Why is it important for us to diagnose CAPA?

There have been several studies that have shown excess mortality rates of 16% & 25% compared with patients without evidence for aspergillosis

pubmed.ncbi.nlm.nih.gov/33333012/
11/
Overall, diagnostic modalities include:
❤️Histopath examination of lungs
🧡Tracheal aspirates
💛BAL culture
💜Aspergillus PCR from BAL
💚Serum galactomannan (GM)
💙BAL galactomannan
🤎Serum beta-d-glucan
12/
We can try to diagnose with sputum cultures, but their sensitivity in ICU pts for diagnosis of IPA does not exceed 50%, and we have previously reviewed the test characteristics of both serum and BAL GM in ICU patients

13/
There are several proposed algorithms for diagnosing CAPA

Given how novel the disease entity is, it's difficult to come up with universal definitions

This algorithm is nice in that it provides helpful tips and different pathways with BAL vs no BAL

pubmed.ncbi.nlm.nih.gov/32703771/ Image

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More from @FilaMentor

16 Feb
1/
This is the first of 2 tweets! #GalactoMagic

37M w/ cirrhosis on the liver transplant list has been in the ICU for 1 week for management of hepatorenal syndrome. His initial presentation was notable for fevers & dyspnea, but he was otherwise hemodynamically stable w/o hypoxia
2/
His fevers continued & then developed worsening hypoxemia requiring 2L O2. CT chest showed bilateral sub-centimeter lung nodules. Labs are sent and a diagnosis of Crypto is made. Serum beta-d-glucan later results; what would you expect its value to be? (ref range <31 pg/mL)?
1/7
Answer: <31. We've learned that there are 3 fungi that don't cause a + serum BDG: Blasto, Mucorales, Crypto. Looking at the Venn diagram, crypto is on the perimeter of the BDG circle. Crypto rarely causes a +BDG, and when it does, it's low level +

pubmed.ncbi.nlm.nih.gov/29125373/
Read 9 tweets
11 Feb
1/
This is the first of 2 tweets! #GalactoMagic

62M w/ PMHx of liver transplant 8 months ago presents w/ 3 weeks of cough & fevers. He recently moved from Indiana (where he had his transplant) to Florida. He has been adherent to his meds (tacro, mycophenolate, pred, trim/sulfa)
2/
T 38.1C, HR 99, BP 115/85, RR 16, 95% on RA. Exam notable for shallow ulcer on soft palate. CT chest shows new nodules bilaterally in lung parenchyma. Serum BDG assay is 85 (positive>80), serum GM index is 0.55 (positive>0.5). Patient likely has which infection?
1/8
This patient from Indiana had a liver transplant 8 months ago & presented w/ a palate ulcer, pulm nodules, & a positive BDG & GM, all of which point to disseminated histo
Read 10 tweets

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