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@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Severe inflammation may increase mitochondrial oxidative stress
sciencedirect.com/science/articl…

Hypoxia in occluded regions likely exacerbates
ncbi.nlm.nih.gov/pubmed/29601945

Glycolysis increases
ncbi.nlm.nih.gov/pmc/articles/P…

PPP should slow in hypoxia (caveat: cancer paper)
ncbi.nlm.nih.gov/pubmed/24005892
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Ascorbate is depleted by hypoxia.
ncbi.nlm.nih.gov/pubmed/9128902

Ascorbate mitigates some effects of hypoxia.
physoc.onlinelibrary.wiley.com/doi/pdf/10.111…
ncbi.nlm.nih.gov/pmc/articles/P…
The IV vitamin C cancer people may have a point tbh, supportive anyway.

Likely helps here as well:
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Not sure how far ascorbate must fall for RBC fragility, but can do in vivo; makes spherocytes
ncbi.nlm.nih.gov/pmc/articles/P…

Spherocytes promote hypercoagulability, thrombosis
thrombosisresearch.com/article/S0049-…

Ascorbate also needed for immune response
ncbi.nlm.nih.gov/pmc/articles/P…
Further depletes.
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t In extremis, chronic ascorbate depletion increases fibrinogen but depletes other factors by oxidation, finally reducing coagulability.

But I have doubts in acute setting.

Thrombi in tissue samples also suggest against.

Looking.

academic.oup.com/nutritionrevie…

sciencedirect.com/science/articl…
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Sepsis and interleukin therapy studies: higher than frank scurvy
ccforum.biomedcentral.com/articles/10.11…
cancerres.aacrjournals.org/content/canres…
ncbi.nlm.nih.gov/pubmed/14946592

Local depletion may not systemically oxidize clotting factors?

Scurvy hemorrhage is partly connective-tissue-mediated
ncbi.nlm.nih.gov/books/NBK49318…
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Ascorbate depletion impairs adrenals; min. conc. unclear (study used high conc).

11 beta-hydroxylase impaired. 17-hydroxylase uninvolved. Main role is protecting cytochrome.
ncbi.nlm.nih.gov/pubmed/2990871

ACTH prompts ascorbate secretion
academic.oup.com/ajcn/article/8…
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Impaired 11 beta-hydroxylase interesting; see:
en.wikipedia.org/wiki/Congenita…

May further promote edema, hypertension?

May deplete cortisol; suggests corticosteroid use?
Sepsis-relevant:
ncbi.nlm.nih.gov/pubmed/18691099
But controversial; also some trials may dose too high or be too uniform.
@DmclDoc @lewistlc @Pharmaheretic @medusimal @farid__jalali @__philipn__ @BioBreakout @aknappjr @sm0b0t Overall, this proposal looks compatible with the inflammatory and ACE-2-driven processes discussed above.

This one should still occur to some extent in other severe pneumonia, though.

The ACE-2 depletion side likely exacerbates outcomes, including the conditions suspected here.
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ice9
@__ice9
@aknappjr @lewistlc @csentropy @farid__jalali @BioBreakout @Pharmaheretic @medusimal Hyaline membrane formation already suffices to begin impairing gas exchange on epithelial side even in advance of endothelial dysfunction and partial occlusion within microvasculature--

medicinenet.com/script/main/ar…
lay source but decent

Impairment on both sides of alveolar wall.
@aknappjr @lewistlc @csentropy @farid__jalali @BioBreakout @Pharmaheretic @medusimal Matches earlier suspicions on accumulation of debris, lack of surfactant


ACE2 expressed most heavily within lungs by goblet cells, ciliated cells.

Virus kills them selectively, lysate accumulates, hyaline membrane forms. Beginning of 'silent hypoxemia'.
@aknappjr @lewistlc @csentropy @farid__jalali @BioBreakout @Pharmaheretic @medusimal @cameronks I think we may have some answers for your observations re: silent hypoxemia
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ice9
@__ice9
@monarchdiaries @lewistlc @aliostad @BioBreakout @aknappjr @YinPD @InceptionCap @hcornea @icedoc61 It's real.

@monarchdiaries @lewistlc @aliostad @BioBreakout @aknappjr @YinPD @InceptionCap @hcornea @icedoc61 The literature is very extensive. And heparin among other things apparently can indeed work.

@monarchdiaries @lewistlc @aliostad @BioBreakout @aknappjr @YinPD @InceptionCap @hcornea @icedoc61 The only significant disputes I see involve *which* anticoagulants to use-- not whether or not to use them.

Nebulized heparin looks better than systemic.

pubmed.ncbi.nlm.nih.gov/31262641/

ejbronchology.eg.net/article.asp?is…

atsjournals.org/doi/10.1164/rc…

atm.amegroups.com/article/view/1…

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ice9
@__ice9
@randicus79 @InceptionCap @YinPD @BioBreakout @AppleHelix @aknappjr Currently, I see the strongest evidence for [hydroxy]chloroquine, umifenovir (weak but non-negligible), tocilizumab (probably also sarilumab and siltuximab), nebulized interferon alpha-2b

These also show some apparent success in human use: favipiravir, ciclesonide, remdesivir
@randicus79 @InceptionCap @YinPD @BioBreakout @AppleHelix @aknappjr For combination prophylactic antibiotics and anti-inflammatories, azithromycin appears to be a reasonable choice. Could perhaps substitute doxycycline or minocycline in patients with QT prolongation issues -- they also have a history of use in this role.
@randicus79 @InceptionCap @YinPD @BioBreakout @AppleHelix @aknappjr There are some indications that ARBs like losartan may be useful in moderate and worse cases.

There is circumstantial evidence that anticoagulants may become useful in critical cases, for preventing intravascular coagulopathy in the microvasculature of the lungs.
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Peter Österberg, Ph.D, W&O Psychology
@Genlearnman
Another non-scientific paper urging for a #plantbased, #GardenofEden, #vegan-oriented alternative to real food (Bonnet et al 2020, sciencedirect.com/science/articl…) #Cherrypicking

#Science, on the other hand, shows that real food is no issue for climate
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Ben See
@ClimateBen
The map on the left shows countries suffering from increasingly extreme water stress this decade (red & dark brown).

The map on the right shows countries whose groundwater will start running out this decade (yellow) or soon after (light green).

We need solidarity for survival.
By 2025, it is estimated that around 5 billion people, out of a total population of around 8 billion, will be living in countries experiencing water stress.

By 2030 4 billion will live with high water stress. sciencedirect.com/science/articl…
Already today, 2 billion people live in countries with extremely high water stress.

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David T. Isaac
@DIsaac8
With a certain Ratepayers Association back in the news, I thought I'd take a look at the "facts" page on the group's website. #ldnont
Fact 1: Calgary's Supervised Consumption Site ("SCS") led to an increase in crime.

The source for this is, oddly, a letter to the editor to a Barrie newspaper, although there were reports of increased crime near the cite (but see facts 3 and 4 below).
What the Association doesn't note with this fact is that the Calgary SCS prevented 1,055 overdoses, overdose events decreased by 336% due to the SCS's drug safety education, and each $1 spent on an SCS saves the province $5 in other costs.

s3.documentcloud.org/documents/6355…
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Laura Horton, MD
@LHortonGI
Pathophys tickler / #AMreport preview: I once cared for a woman who needed plasma exchange in the 3rd trimester of pregnancy. The transfusionist pointed out something odd...guesses as to the cause? [Hint: biliverdin isn't the only green substance in the human body...]
@BostonChiefs @tony_breu @JonXLiMD
Thanks for the excellent responses! We brainstormed about what green substances could cause this patient to have green plasma... biliverdin came to mind first, but didn't make sense for this patient. Incidentally, high biliverdin levels cause lizards to have bright green blood:
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