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**Heme Review**

The official podcast of Chubbyemu. Heme Review is a podcast about case reports in medicine. Each episode will tell a patient’s story, while teaching about the pathogenesis of disease, the treatment modalities and the dilemmas that arise during their care.

Latest Episodes:

A Brief Discussion Of Dinitrophenol In The Setting Of Weight Loss Mar 03, 2021

Show notes

Patient CE's personal recount of case: https://youtu.be/7BpymtR2vpA

Patient CE's Interview: https://youtu.be/o15HCjtSkug

Chubbyemu video on this case: https://youtu.be/ChPeG19qKUo

Heme Review video version: https://youtu.be/jgDUMNaVqHg

2,4-Dinitrophenol (DNP) is a chemical that is not approved for weight loss in the United States. It is a classic case of efficacy, but without safety in the setting of weight loss. This setting of weight loss can be prone to chemical misuse, further exacerbating understanding in human systems. Christopher is one of 2 - 3 cases documented in literature to have survived an accident with DNP for weight loss. As of 2021, one organization has permission from the US FDA to investigate DNP in some neurodegenerative disorders. These are rare diseases with limited standards of care, therefore extenuating circumstances to find anything that could potentially improve patient outcomes.

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References:

Role of dantrolene in dinitrophenol (DNP) : A continuing question? Am J Emerg Med. 2019 Jun;37(6):1216.e1-1216.e2. https://pubmed.ncbi.nlm.nih.gov/30948257/

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity . J Med Toxicol. 2011 Sep;7(3):205-12. https://pubmed.ncbi.nlm.nih.gov/21739343/

Ambient temperature and mortality from unintentional . JAMA. 1998 Jun 10;279(22):1795-800. https://pubmed.ncbi.nlm.nih.gov/9628710/

Dinitrophenol as a Medicine. Cells. 2019 Mar; 8(3): 280. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468406/

The Interaction of Highly Active Uncouplers With Mitochondria. Biochimica et Biophysica Acta, 639 (1981) 225-242.

Beware the yellow slimming pill: fatal 2,4-dinitrophenol. BMJ Case Rep. 2016 Apr 4;2016. https://pubmed.ncbi.nlm.nih.gov/27045052/

Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate. BMJ Case Rep. 2018 Dec 19;11(1):e225323. https://pubmed.ncbi.nlm.nih.gov/30573533/

The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431-44. https://pubmed.ncbi.nlm.nih.gov/4388239/

The mechanism of uncoupling of oxidative phosphorylation by 2,4-dinitrophenol. J Biol Chem. 1967 Oct 25;242(20):4577-83. https://pubmed.ncbi.nlm.nih.gov/4964808/

MECHANISMS OF DINITROPHENOL TOXICITY. Simon E.W. Biological Reviews. Vol 28. (4). Nov 1953.

Identification and Importance of Brown Adipose Tissue in Adult Humans. https://www.nejm.org/doi/full/10.1056/NEJMoa0810780

Mitochondrial uncoupling as a target for drug development for the treatment of obesity. Obes Rev. 2001 Nov;2(4):255-65. https://pubmed.ncbi.nlm.nih.gov/12119996/

LC-MS-MS analysis of 2,4-dinitrophenol and its phase I and II metabolites. J Ana Toxicol. Jan-Feb 2007;31(1):55-61. https://pubmed.ncbi.nlm.nih.gov/17389084/

Uncouplers of oxidative phosphorylation. Environ Health Perspect. 1990 Jul;87:213-8. https://pubmed.ncbi.nlm.nih.gov/2176586/

Texas Woman Charged with Selling Misbranded

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug

The Body After Eating Several Pounds Licorice Candy Oct 05, 2020

Show notes

Based on N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420

Chubbyemu video of this case: https://open.spotify.com/episode/77z8mZGbmBI4E2JtA8GXsh?si=k_qV_IkrQiqTGpn8EXK61Q

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Licorice candy has glycyrrhizin which increases cortisol (stress hormone) levels in the body. This causes hypokalemia. Hypo- low. Kal- kalium (potassium). emia- presence in blood. Potassium signals muscle relaxation. Low potassium, low relaxation. Heart can't relax, then it stops. Real licorice candy is not easy to get in the United States. It's not at big chain grocery stores. Most of what you can buy from the big brands is licorice flavored, and won't do this.

References:

A 54-Year-Old Man with Sudden Cardiac Arrest. N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420

The Pharmacological Activities of Glycyrrhizinic Acid (“Glycyrrhizin”) and Glycyrrhetinic Acid. Sweeteners. 2018 : 245–261. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123798/

Sustained Leukocyte Count during Rising Cortisol Level. Acta Haematologica 118(2):73-6. https://www.researchgate.net/publication/6298458

https://www.nobelprize.org/prizes/medicine/1964/bloch/lecture/

Licorice-Induced Hypermineralocorticoidism. N Engl J Med 1991; 325:1223-1227. https://www.nejm.org/doi/full/10.1056/NEJM199110243251706

Young WF, et. al. Apparent mineralocorticoid excess syndromes (including chronic licorice ingestion). In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2019.

Quinkler M, Stewart PM. Hypertension and the cortisol-cortisone shuttle. J Clin Endocrinol Metab 2003; 88:2384.

Funder JW. Apparent mineralocorticoid excess. J Steroid Biochem Mol Biol 2017; 165:151.

Funder JW. 11 beta-Hydroxysteroid dehydrogenase: new answers, new questions. Eur J Endocrinol 1996; 134:267.

TikTokers Taking Too Much Benadryl Sep 15, 2020

Show notes

YouTube Video Version: https://youtu.be/ZNA_NtcutYY

Chubbyemu Video: https://youtu.be/NaAFOrudj0g

References:

The Pharmacology and Use of H1-Receptor-Antagonist. N Engl J Med 1994; 330:1663-1670

Advances in H1-Antihistamines. N Engl J Med 2004; 351:2203-2217

Cardiac arrest caused by diphenhydramine overdose. Acute Med Surg. 2018 Oct; 5(4): 380–383.

IV Lipid Emulsion Infusion in the Treatment of Severe Diphenhydramine. Am J Case Rep. 2019 May 29;20:758-763.

Diphenhydramine with Intraventricular Conduction Delay Treated with Hypertonic Sodium Bicarbonate and IV Lipid Emulsion. West J Emerg Med. 2014 Nov; 15(7): 855–858.

Diphenhydramine in a 26-year-old Woman. J Emerg Nurs. 2008 Dec;34(6):543-4.

Heatstroke (from a Bitcoin Mining Accident) Aug 15, 2020

Show notes

YouTube Video Version: https://youtu.be/QSXzRWiuvxE

Chubbyemu video of this case ▶️ https://youtu.be/fr8bp8a2QS4

The Body After Drinking A Snowglobe ▶️ https://youtu.be/elzijduKNS8

The Body After 2 Gallons Coffee In 3 Hours ▶️ https://youtu.be/rn-WLpa_nyQ

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Music by @Lifeformed

Heatstroke is a serious problem and the heatwaves that cause it, claim more lives on average than any other weather event in USA. While generally thought to affect the elderly and the very young, it can affect people of all ages, not just because of the heat in the environment (classic heatstroke) but also because of activity (exertional heatstroke). The problems caused by heatstroke sometimes happen but don't appear clinically, like GI ischemia.

Bitcoin is a decentralized cryptocurrency that's used in peer to peer transactions. This happened in 2011 when individual people could still mine coins, but now, miners are usually pools or in large facilities in places that have cheap electricity and cool climate to save on computer cooling costs.

The followup: https://web.archive.org/web/20110612111539/http://www.bitcoinminingaccidents.com/

References:

0 Heat Stroke. Compr Physiol 5:611-647, 2015.

1 Heatstroke N Engl J Med 2019; 380:2449-2459.

2 Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am J Physiol Heart Circ Physiol 280: H509–H521, 2001.

3 The Impact of Mild Heat Stress During Prolonged Running On Gastrointestinal Integrity, Gastrointestinal Symptoms, Systemic Endotoxin and Cytokine Profiles. Int J Sports Med 2018; 39: 255–263.

4 Heat stroke: Role of the systemic inflammatory response. J Appl Physiol (1985). 2010 Dec;109(6):1980-8.

5 Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J. 1988 May 7;73(9):533-6.

6 Pathogenesis of nonocclusive ischemic colitis. Ann Surg. 1986 Jun;203(6):590-9.

Methanol Hand Sanitizer Aug 01, 2020

Show notes

Methanol-contaminated hand sanitizer has been on sale in the USA during COVID-19 pandemic. The FDA has issued a warning against this, and have listed the brands. Most stores that are selling these brands have pulled them from shelves.

Methanol is a toxic alcohol that can cause blindness. Its antidote is ethanol, which is the alcohol that people drink casually, however management needs to be done by a healthcare professional, as methanol hangs around in the body for several days.

The case presented here predates the pandemic by almost 20 years. However, methanol skin absorption has been identified as an industrial work hazard since the early 20th century.

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References:

[0] Case report: Percutaneous absorption and distribution of methanol in a homicide.J Ana Toxicol. 2005 Oct;29(7):734-7. https://pubmed.ncbi.nlm.nih.gov/16419410/

[1] FDA Methanol List: https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-consumers-should-not-use

[2] B.Dutkiewicz, J.Konczalik, and W.Karwaki. Skin absorption and per os administration of methanol in men. Int. Arch. Occup. Environ. Health 47(1): 81-88 (1980).

[3] Material Safety Data Sheet. SNAP Octane Booster, Product #8-290, SNAP Products Inc. Pandora, OH, 1993.

Crystallopathies Jul 27, 2020

Show notes

This episode is about the pathophysiology on crystallopathies. The cellular pathways involved unify multiple concepts and multiple branches of medicine, from toxicology to cardiology to rheumatology and oncology.

Heme Review YouTube Channel: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA

References:

[0] Crystallopathies. N Engl J Med 2016; 374:2465-2476. https://www.nejm.org/doi/full/10.1056/NEJMra1601611

[1] Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death & Disease. Volume 10, Article number: 128 (2019). https://www.nature.com/articles/s41419-019-1413-8

[2] The Inflammasome. Molecular Cell. VOLUME 10, ISSUE 2, P417-426, AUGUST 01, 2002. https://www.cell.com/molecular-cell/fulltext/S1097-2765(02)00599-3

[3] Silica crystals and aluminum salts mediate NALP-3 inflammasome activation via phagosomal destabilization. Nat Immunol. 2008 Aug; 9(8): 847–856. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834784/

[4] Tumor Cell–Derived IL1β Promotes Desmoplasia and Immune Suppression in Pancreatic Cancer. Cancer Res 2020;80:1088–101. https://cancerres.aacrjournals.org/content/80/5/1088

The Body After Drinking A Snowglobe (High Anion Gap Metabolic Acidosis) Jul 21, 2020

Show notes

Chubbyemu case: https://youtu.be/UrbylXMU8Mw

Most snowglobes are just made of water, but some can contain ethylene glycol. Most of those usually don't contain enough ethylene glycol to cause damage, but keep the word "usually" in mind. A homemade snowglobe can contain concentrations of anything, which is what happened in this case.

Ethylene glycol can cause a profound high anion gap metabolic acidosis, and we'll explain the science, chemistry and physiology behind that in this episode.

References:

Delayed ethylene glycol presenting with abdominal pain and multiple cranial and peripheral neuropathies: a case report. Journal of Medical Case Reports volume 4, Article number: 220 (2010).

Multiple Cranial Nerve Deficits After Ethylene Glycol. Ann Emerg Med. 1991 Feb;20(2):208-10. https://pubmed.ncbi.nlm.nih.gov/1996809/

Antidotes OH that form toxic metabolites. Br J Clin Pharmacol. 2016 Mar; 81(3): 505–515. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4767193/

Toxic Alcohols. N Engl J Med 2018; 378:270-280. https://www.nejm.org/doi/full/10.1056/NEJMra1615295

Ethylene glycol ingestion masked by concomitant ethanol ingestion. Case Reports 2012;2012:bcr1220115326. https://casereports.bmj.com/content/2012/bcr.12.2011.5326

Challenges in the Diagnosis of Ethylene Glycol Poisoning. Ann Clin Biochem. 2014 Mar;51(pt2):167-78. https://pubmed.ncbi.nlm.nih.gov/24215789/

Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore) 1977;56:38-54.

Uribarri J, Oh MS, Carroll HJ. D-lactic acidosis: a review of clinical presentation, biochemical features, and pathophysiologic mechanisms. Medicine (Baltimore) 1998;77:73-82.

Judge BS. Metabolic acidosis: differentiating the causes in the poisoned patient. Med Clin North Am 2005;89:1107-1124.

Kosten TR, O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med 2003;348:1786-1795. https://www.nejm.org/doi/full/10.1056/NEJMra020617

A 49 Year Old Man With Obtundation Followed By Agitation And Acidosis. N Engl J Med 2015; 372:465-473. https://www.nejm.org/doi/full/10.1056/NEJMcpc1410940

Integration of Acid-Base And Electrolyte Disorders. N Engl J Med 2014; 371:1821-1831. https://www.nejm.org/doi/full/10.1056/NEJMra1215672

Calcium Kidney Stones. N Engl J Med 2010; 363:954-963. https://www.nejm.org/doi/full/10.1056/NEJMcp1001011

What Happens In A Caffeine Overdose May 19, 2020

Show notes

Max recommended amount of caffeine per day is 400mg.

@Chubbyemu case report video ► https://youtu.be/wj_AOzSSDMM

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Music by @Lifeformed

Some caffeine is OK. 1-2 cups of coffee can generally be ok. Unreasonably large amounts of caffeine NOT OK.

References:

[0] Hensher C, Vogel J. Insulin Euglycemic Therapy in the Treatment of Caffeine. Chest. 2020 May;157(5):e145-e149. https://pubmed.ncbi.nlm.nih.gov/32386647/

[1] Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion. J Control Release. 2015 Jan 28; 198: 62–70.

[2] Rall TW, Sutherland EW. Formation of a Cyclic Adenine Ribonucleotide By Tissue Particles. J Biol Chem 1958, 232:1065-1076.

[3] A Case of Exercise-Induced Rhabdomyolysis Associated With A Weight Loss Dietary Supplement. Military Medicine, 172, 6:656, 2007.

[4] Yamada Y, et. al. The mode of action of caffeine on catecholamine release from perfused adrenal glands of cat. Br. J. Pharmacol. (1989), 98, 351-356.

[5] Effects of Caffeine on Plasma Renin Activity, Catecholamines and Blood Pressure. N Engl J Med 1978; 298:181-186.

[6] Caffeine resulting in severe rhabdomyolysis and acute renal failure. American Journal of Emergency Med 32 (2014) 111.e3-111.e4.

[7] Eteng, MU, et. al. Recent advanced in caffeine and theobromine toxicities: a review. Plant Foods for Human Nutrition 51: 231-243, 1997.

[8] Jabbar SB, et. al. Caffeine: A case report and review of literature. Am J Forensic Med Pathol. Vol 34, N4, Dec 2013.

[9] Bioh G. et. al. Survival of caffeine. BMJ Case Rep 2013. bcr-2012-007454.

A Future Of Medicine May 04, 2020

Show notes

Support this podcast! https://anchor.fm/chubbyemu/support

Video version of this video: https://youtu.be/iVt5BpoTHYg

Tweet me: https://twitter.com/HemeReview

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Music by Lifeformed: http://lifeformed.bandcamp.com/

References:

[0] Chapman PB et. al. Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study.Ann Oncol. 2017 Oct 1;28(10):2581-2587. https://www.ncbi.nlm.nih.gov/pubmed/28961848

[1] Chapman PB. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. N Engl J Med 2011; 364:2507-2516. https://www.nejm.org/doi/full/10.1056/NEJMoa1103782

[2] Amy Harmon. New Drugs Stir Debate on Rules of Clinical Trials. New York Times, September 19, 2010. https://www.nytimes.com/2010/09/19/health/research/19trial.html

The Farmer Who Removed His Skin Cancer With A Pocket Knife Apr 13, 2020

Show notes

Support this podcast! https://anchor.fm/chubbyemu/support

Video version of this podcast: https://www.youtube.com/watch?v=bxGS07U-B98

Video by Chubbyemu: A Farmer Removed His Own Skin Cancer With A Pocket Knife. This Is What Happened To His Brain. https://www.youtube.com/watch?v=KKaJhQBusH8

References:

- Melanoma brain metastases: current areas of investigation and future directions. Cancer J. 2017 Jan-Feb; 23(1): 68–74. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300745/

- The metastatic cycle: metastatic niches and cancer cell dissemination. J Dtsch Dermatol Ges. 2014 Nov;12(11):1012-9. https://www.ncbi.nlm.nih.gov/pubmed/25307562

- BRAF Targets in Melanoma: Biological Mechanisms, Resistance, and Drug Discovery. Humana Press. 2015.

- Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature2002;417:949-954. https://www.ncbi.nlm.nih.gov/pubmed/12068308?dopt=Abstract

- MAP kinase pathways: the first twenty years. Biochim Biophys Acta. 2007 Aug;1773(8):1150-60. Epub 2006 Nov 15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2043147/

Music by Lifeformed. Please check out his music at his Bandcamp: https://lifeformed.bandcamp.com

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