Heme Review

Collaborator: Dr Katherine JohnsIf you don't need to put it in your body, don't put it in your body.These cases are patients who I, or my colleagues have seen. They are de-identified and many instances have been presented in more depth in an academic setting. These videos are not individual medical advice and are for general educational purposes only. I do not give medical advice over the internet.References:A family cluster of nitrite poisoning, Suzhou City, 2013. Western Pac Surveill Response J. 2013 Jul 30;4(3):33-6. https://pmc.ncbi.nlm.nih.gov/articles/PMC3854094/Human safety controversies surrounding nitrate and nitrite in the diet. https://pubmed.ncbi.nlm.nih.gov/22487433/A mitochondrial superoxide theory for oxidative stress diseases and aging. https://pmc.ncbi.nlm.nih.gov/articles/PMC4306659/Proposed mechanism of nitrite-induced methemoglobinemia. https://pubmed.ncbi.nlm.nih.gov/15892615/Methylene Blue. https://www.ncbi.nlm.nih.gov/books/NBK557593/Methemoglobinemia. https://www.ncbi.nlm.nih.gov/books/NBK537317/Methylene Blue in Goldfrank's ToxicologyPriapism. https://www.ncbi.nlm.nih.gov/books/NBK459178/Methylene blue as a means of treatment for priapism caused by intracavernous injection to combat erectile dysfunction. https://pubmed.ncbi.nlm.nih.gov/15198160/Pharmacologically-induced Recreational Priapism: Case Report and Review. https://pmc.ncbi.nlm.nih.gov/articles/PMC7676772/PharmGKB summary very important pharmacogene information for G6PD. https://journals.lww.com/jpharmacogenetics/citation/2012/03000/pharmgkb_summary__very_important_pharmacogene.8.aspxThe Methylene Blue Baby. N Engl J Med 1989;320:1756-1757. Methylene blue as an antidote for poisoning. J Lab Clin Med. 1933;19:166–71.Methylene blue for distributive shock: a potential new use of an old antidote. J Med Toxicol. 2013;9:242–9.A review of methylene blue treatment for cardiovascular collapse. J Emerg Med. 2014;46:670–9.The role of monoamine oxidase inhibitors in depression treatment guidelines. https://pubmed.ncbi.nlm.nih.gov/22951237/FDA to Revoke Authorization for the Use of Red No. 3 in Food and Ingested Drugs. https://www.fda.gov/food/hfp-constituent-updates/fda-revoke-authorization-use-red-no-3-food-and-ingested-drugsMethylene Blue in the Treatment of Poisonings Associated with Methemoglobinemia. https://www.nejm.org/doi/abs/10.1056/NEJM193306012082205Lawmakers Press Amazon on Sales of Chemical. https://www.nytimes.com/2022/02/04/technology/amazon-suicide-poison-preservative.html

Original Report: https://www.nejm.org/doi/abs/10.1056/NEJMc2500231

References:Syphilis – Its early history and Treatment until Penicillin and the Debate on its Origins. https://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/Establishment of the Nichols strain as the type strain of Treponema pallidum. https://pmc.ncbi.nlm.nih.gov/articles/PMC11868658/In vitro assay to demonstrate high-level erythromycin resistance of a clinical isolate of Treponema pallidum.. https://pmc.ncbi.nlm.nih.gov/articles/PMC172128/Phylogenetic and genetic characterization of Treponema pallidum strains from syphilis patients in Japan by whole-genome sequence analysis from global perspectives. https://pmc.ncbi.nlm.nih.gov/articles/PMC7862685/ Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis. https://pmc.ncbi.nlm.nih.gov/articles/PMC8612932/Near-Universal Resistance to Macrolides of Treponema pallidum in North America. https://www.nejm.org/doi/full/10.1056/NEJMc2314441

Chubbyemu video: https://open.spotify.com/episode/5BXEnVu8h0UWvlfmkwy3Xv?si=1XFT34Q9Q06okvMB2UgNKg

Selected References:
Intravenous mushroom poisoning. https://pubmed.ncbi.nlm.nih.gov/4025991/

The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance. https://pubmed.ncbi.nlm.nih.gov/18839291/

Clinical toxicology of cyanide. https://pubmed.ncbi.nlm.nih.gov/3526995/

Probing the oxygen binding site of cytochrome c oxidase by cyanide. https://pubmed.ncbi.nlm.nih.gov/7929065/

Colchicine Gout Approval 2009 https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022351

Chubbyemu is on Spotify now!
Chubbyemu Licorice Video: https://open.spotify.com/episode/77z8mZGbmBI4E2JtA8GXsh?si=k_qV_IkrQiqTGpn8EXK61Q

References:
A bradykinin-potentiating factor (bpf) present in the venom of bothrops jararaca. https://pmc.ncbi.nlm.nih.gov/articles/PMC1704050/

UpToDate, Choice of drug therapy in primary (essential) hypertension.

Primary Hyperaldosteronism. https://www.ncbi.nlm.nih.gov/books/NBK539779/
NEJM Case 24-1992.

Dr Pavlos Msaouel: https://faculty.mdanderson.org/profiles/pavlos_msaouel.html
0:00 Pretext and context MD Anderson Cancer Center
1:42 The Early Experiences That Shaped Dr Msaouel
3:39 The System of Cancer Research In the United States
5:25 FDA Drug Approvals and Special Designations For Oncology
11:09 A trade-off in our current system
12:35 Whoops 😞 I misspoke
14:35 Randomized trials are not supposed to be representative of a population
18:10 Inference for the treatment of Katie Coleman (metastatic oncocytoma)
25:12 It is much more valuable to refute hypotheses than to confirm them
28:05 All Models Are Wrong, But Some Are Useful
30:05 Recasting the Bias-Variance Trade-off as the Patient Relevance-Robustness Trade-off
33:38 High Relevance, Low Robustness: Subjective Bayes
34:46 High Robustness, Low Relevance: Pure Randomization
41:47 Signal To Noise Ratio
45:49 The Big Data Paradox
53:41 How the Big Data Paradox fits in with Katie Coleman's case
54:33 How the Big Data Paradox fits in with other branches of medicine
57:54 How do we rectify subjectivity in The Truth?
01:00:43 How do we address the problems introduced by the Big Data Paradox?
01:04:21 Duality in nature and a Twitter argument re: the Evidence-Based Deep Medicine Iceberg
01:07:03 Why the ideas coming from MD Anderson are coming from MD Anderson
01:09:39 Where you can find Dr Msaouel

Dr Msaouel: https://twitter.com/PavlosMsaouel
Heme Review: https://twitter.com/HemeReview

Produced by ⁠ @chubbyemu ⁠

Production Assistant: Nick Brown
Secret channel:  @BigEmus 

Cancer Patient Speaks With Her Oncologist ► https://youtu.be/Nddft_nc3Yc
A Woman Had A Headache Lasting 3 Days (Katie's case) ► https://www.youtu.be/i9fLEvgZzRE

References:

Stephen Senn. Statistical Issues in Drug Development.

Why representativeness should be avoided. https://academic.oup.com/ije/article/42/4/1012/656034

Commentary: Representativeness is usually not necessary and often should be avoided. https://academic.oup.com/ije/article/42/4/1018/658638

Impervious to Randomness: Confounding and Selection Biases in Randomized Clinical Trials. https://www.tandfonline.com/doi/full/10.1080/07357907.2021.1974030

A Causal Framework for Making Individualized Treatment Decisions in Oncology. https://www.mdpi.com/2072-6694/14/16/3923

Causal Diagram Techniques for Urologic Oncology Research. https://www.sciencedirect.com/science/article/pii/S1558767320301932

Causal inference and the data-fusion problem.
https://www.pnas.org/doi/10.1073/pnas.1510507113

Causal Inference: What If. Miguel A Hernán and James M. Robins. https://www.hsph.harvard.edu/miguel-hernan/wp-content/uploads/sites/1268/2023/04/hernanrobins_WhatIf_31mar23.pdf

There is Individualized Treatment. Why Not Individualized Inference? https://arxiv.org/abs/1510.08539

Unrepresentative big surveys significantly overestimated US vaccine uptake. https://www.nature.com/articles/s41586-021-04198-4

Unrepresentative Big Surveys Significantly Overestimate US Uptake https://arxiv.org/pdf/2106.05818.pdf

Statistical Modeling: The Three Cultures. https://hdsr.mitpress.mit.edu/pub/uo4hjcx6/release/1

How “centaur AI” will radically reshape the future of healthcare. https://bigthink.com/health/how-centaur-ai-will-radically-reshape-the-future-of-healthcare/