Heme Review
Syphilis Is Changing Like Weve Never Seen... In Seattle
updated
Produced by @chubbyemu
Audio only version: https://spotifyanchor-web.app.link/e/C3WPkgNWZzb
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: twitter.com/PavlosMsaouel
Heme Review: twitter.com/HemeReview
Production Assistant: Nick Brown
Secret channel: @BigEmus
Cancer Patient Speaks With Her Oncologist ► youtu.be/Nddft_nc3Yc
A Woman Had A Headache Lasting 3 Days (Katie's case) ► youtu.be/i9fLEvgZzRE
References:
Stephen Senn. Statistical Issues in Drug Development.
Why representativeness should be avoided. academic.oup.com/ije/article/42/4/1012/656034
Commentary: Representativeness is usually not necessary and often should be avoided. academic.oup.com/ije/article/42/4/1018/658638
Impervious to Randomness: Confounding and Selection Biases in Randomized Clinical Trials. tandfonline.com/doi/full/10.1080/07357907.2021.1974030
A Causal Framework for Making Individualized Treatment Decisions in Oncology. mdpi.com/2072-6694/14/16/3923
Causal Diagram Techniques for Urologic Oncology Research. sciencedirect.com/science/article/pii/S1558767320301932
Causal inference and the data-fusion problem.
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? arxiv.org/abs/1510.08539
Unrepresentative big surveys significantly overestimated US vaccine uptake. nature.com/articles/s41586-021-04198-4
Unrepresentative Big Surveys Significantly Overestimate US Uptake 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. bigthink.com/health/how-centaur-ai-will-radically-reshape-the-future-of-healthcare
Happened while filming this video: youtu.be/LKNfFm0QDXQ
Music by @Lifeformed: lifeformed.bandcamp.com
Timestamps:
0:00 Pretext
0:29 I Used To Self-Mix Supplements
2:25 Mixing The Wrong Supplements Causes Accidents
2:54 Caffeine Mechanism of Action
4:12 Caffeine and Sleep
5:09 Why Caffeine Isn't As "Strong" As Other Stimulants
5:52 How Caffeine Dependency Develops
7:09 Chubbyemu's Caffeine Withdrawal
11:15 Caffeine Withdrawal Pharmacobiology
References:
The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A1 Receptor. mdpi.com/1422-0067/22/1/320
Caffeine Withdrawal. ncbi.nlm.nih.gov/books/NBK430790
A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. pubmed.ncbi.nlm.nih.gov/15448977
Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. pubmed.ncbi.nlm.nih.gov/20492310
Coffee, CYP1A2 genotype, and risk of myocardial infarction. pubmed.ncbi.nlm.nih.gov/16522833
Heme Review Podcast: https://anchor.fm/chubbyemu
Behind the scenes channel: @BigEmus
Music by @Lifeformed ► lifeformed.bandcamp.com
All Heme Review videos (playlist) ► youtube.com/playlist?list=PLAHeV2H_YiGUYhHOF4wRMCuqBIJvrnWqS
Daddy Longlegs by Vengolis
Loxosceles gaucho by Halies
Some images by Getty Images
References:
CMS Malaque, RS Vetter, M Entres. Loxosceles spiders. Critical Care toxicology. link.springer.com/referenceworkentry/10.1007/978-3-319-17900-1_119
Myth: Idiopathic wounds are often due to brown recluse or other spider bites throughout the United States ncbi.nlm.nih.gov/pmc/articles/PMC1071166
Correspondance: Bites of the Brown Recluse Spider. nejm.org/doi/full/10.1056/nejm200505123521922
Spider Bites: Part 1. lacerationrepair.com/wound-blog/spider-bites
Brown Recluse Pest Management Tips for The Spider That's Not As Common As You Think. entomologytoday.org/2018/01/29/brown-recluse-pest-management-tips-for-the-spider-thats-not-as-common-as-you-think/brown-recluse-range-map
The Chilean Recluse. fdacs.gov/content/download/68159/file/Pest_Alert_-_Loxosceles_laeta,_The_Chilean_Recluse.pdf
Brown recluse spider (Loxosceles reclusa) envenomation leading to acute hemolytic anemia in six adolescents. ncbi.nlm.nih.gov/pmc/articles/PMC4902007
Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation. ncbi.nlm.nih.gov/pmc/articles/PMC4119339
Bites of Brown Recluse Spiders and Suspected Necrotic Arachnidism. nejm.org/doi/full/10.1056/NEJMra041184
CASE OF ARACHNOIDISM (SPIDER BITE). jamanetwork.com/journals/jama/article-abstract/265718
Detection of Loxosceles species venom in dermal lesions: A comparison of 4 venom recovery methods.
annemergmed.com/article/S0196-0644(02)04713-3/fulltext
Brown spider (Loxosceles sp.) bite and COVID-19: A case report. sciencedirect.com/science/article/pii/S0041010122000861
Loxosceles intermedia spider envenomation induces activation of an endogenous metalloproteinase, resulting in cleavage of glycophorins from the erythrocyte surface and facilitating complement-mediated lysis. sciencedirect.com/science/article/pii/S000649712036568X?via%3Dihub
Necrotic arachnidism. pubmed.ncbi.nlm.nih.gov/11260528
Brown Recluse Michigan. ncbi.nlm.nih.gov/pmc/articles/PMC8384389
An Infestation of 2,055 Brown Recluse Spiders (Araneae: Sicariidae) and No Envenomations in a Kansas Home: Implications for Bite Diagnoses in Nonendemic Areas. academic.oup.com/jme/article/39/6/948/862215
A Toddler Drank His Mom's Essential Oils: youtu.be/TZr0nt2hxbs
Audio-podcast version of this video: https://anchor.fm/chubbyemu
Interview With a DNP Accident Survivor: youtu.be/o15HCjtSkug
Tweet me: twitter.com/HemeReview
IG me: instagram.com/HemeReview
Patient portrayed by Abram Cutshall
Mom and her toddler portrayed by Megan Pulley and her son
2-4-Dinitrophenol is also an uncoupler of oxidative phosphorylation on top of salicylate
References:
Salicylate Toxicity from Exposure to a Methylsalicylate-Containing Rubefacient. ncbi.nlm.nih.gov/pmc/articles/PMC4786239
Regional variation in percutaneous penetration of 14C cortisol in man. jidonline.org/article/S0022-202X(15)47268-9/pdf
Anatomy and physiology of chronic s pain ncbi.nlm.nih.gov/pmc/articles/PMC5503924
Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. pubmed.ncbi.nlm.nih.gov/10634967
ISPAD Clinical Practice Consensus Guidelines 2018: DKA and the hyperglycemic hyperosmolar state. pubmed.ncbi.nlm.nih.gov/29900641
Salicylates. Goldfrank, Lewis R, and Neal Flomenbaum. Goldfrank's Toxicologic Emergencies. New York: McGraw-Hill, 2006.
Unconscious Uncoupling – Managing pH in Salicylate. Tox and Hound. toxandhound.com/toxhound/phinasa
Counterproductive effects of sodium bicarbonate in DKA. pubmed.ncbi.nlm.nih.gov/8550770
Anti-Inflammatory Drugs in Patients with Ischemic Heart Disease. Journal of Clinical Medicine 10(13):2835
Risk Factors for Cerebral Edema in Children with Diabetic Ketoacidosis. N Engl J Med 2001; 344:264-269. Risk Factors for Cerebral Edema in Children with Diabetic Ketoacidosis
Role of the mitochondrial permeability transition in salicylate toxicity to cultured rat hepatocytes: implications for the pathogenesis of Reye's syndrome. Toxicol Appl Pharmacol . 1997 Dec;147(2):431-41. pubmed.ncbi.nlm.nih.gov/9439738
Audio only version: https://anchor.fm/chubbyemu/episodes/The-Student-Who-Ate-5-Day-Old-Pasta-And-His-Liver-Shut-Down-e1hb47q
Tweet me: twitter.com/hemereview
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Main channel: @chubbyemu
Behind the scenes channel: @BigEmus
A Student Ate 5 Day Old Pasta For Lunch. This Is How His Liver Shut Down.
References:
Fulminant Liver Failure in Association with the Emetic Toxin of Bacillus cereus. nejm.org/doi/full/10.1056/NEJM199704173361604
Sudden Death of a Young Adult Associated with Bacillus cereus Food Poisoning. ncbi.nlm.nih.gov/pmc/articles/PMC3232990
Acute Liver Failure after Ingestion of Fried Rice Balls: A Case Series of Bacillus cereus Food Poisonings. doi.org/10.3390 toxins14010012
Fatal Family Outbreak of Bacillus cereus-Associated Food Poisoning. ncbi.nlm.nih.gov/pmc/articles/PMC1233987
Bacillus cereus and its food poisoning toxins. pubmed.ncbi.nlm.nih.gov/9435100
Liver Zonation – Revisiting Old Questions With New Technologies. frontiersin.org/articles/10.3389/fphys.2021.732929/full
Bacillus cereus food poisoning. nejm.org/doi/full/10.1056/NEJM197801192980306
Tox and Hound: D and Toxin-Induced Hepatic Microvesicular Steatosis toxandhound.com/toxhound/ff-microvesicular-steatosis
ENCEPHALOPATHY AND FATTY DEGENERATION OF THE VISCERA. A DISEASE ENTITY IN CHILDHOOD. pubmed.ncbi.nlm.nih.gov/14055046
Whatever happened to Reye’s syndrome? Did it ever really exist? pubmed.ncbi.nlm.nih.gov/10470768
Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. pubmed.ncbi.nlm.nih.gov/22120519
Prevalence of Alcoholic Fatty Liver Disease Among Adults in the United States, 2001-2016.
pubmed.ncbi.nlm.nih.gov/31063562
Goldfrank's Toxicologic Emergencies 11th ed.
A Mom Tried Keto Diet: youtu.be/W74jOR9V6UA
The Weird Time When Energy Drinks Fixed My Insomnia: youtu.be/d_qKA6KTvs8
Audio Podcast: https://anchor.fm/chubbyemu
Tweet me: twitter.com/hemereview
IG me: instagram.com/hemereview
References:
Mechanism of hypokalemia in magnesium deficiency. Huang CL, Kuo E. J Am Soc Nephrol. 2007;18:2649–2652. pubmed.ncbi.nlm.nih.gov/17804670
Hypophosphatemia and Rhabdomyolysis ncbi.nlm.nih.gov/pmc/articles/PMC371889
A Case of Hemodynamically Unstable Sick Sinus Syndrome Secondary to Refeeding Syndrome ncbi.nlm.nih.gov/pmc/articles/PMC8148626
Review of the Refeeding Syndrome. January 2006Nutrition in Clinical Practice 20(6):625-33.
EMCrit Refeeding Syndrome emcrit.org/ibcc/refeeding
Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008 Jun 28; 336(7659): 1495–1498. ncbi.nlm.nih.gov/pmc/articles/PMC2440847
@chubbyemu energy drink video ► youtu.be/tAtaIZD0Ebs
A Student Ate Only Chips And Fries For 10 Years ► youtu.be/VINtwoyaF_8
A Mom Ate 5 Day Old Sushi 🍣 ► youtu.be/R0d6Dpx2li4
Vitamin B12 deficiency can cause neurologic problems. It's stored in the liver and isn't made in humans. It needs to be sourced via diet.
A Brief Discussion On Renal Medullary Carcinoma: youtu.be/j7WGP6sJBLk
Audio version of this video: https://anchor.fm/chubbyemu/episodes/Interview-With-A-Rare-Renal-Medullary-Carcinoma-Survivor-e167o99
Sickle Cell means Sickle Hemoglobinopathy, including Sickle Cell Disease, Sickle Cell Trait, Beta Thalassemia, Sickle Cell Hemoglobin-C
Contact Cora: twitter.com/RMCAwareness
Cora Facebook: facebook.com/RMCSupport
A Man Felt Pain In His Back. This Is What Happened To His Kidneys.
IG me: instagram.com/hemereview
Tweet me: twitter.com/hemereview
Thank you Dr Nizar Tannir, Dr Pavlos Msaouel, Cora and Herman Connor, and Dr Loren Stagg
Production Assistant: Nick Brown
Renal Medullary Carcinoma is a sickle cell related kidney malignancy that is usually diagnosed in young patients (median age at diagnosis 28 years old). It is considered a rare malignancy but likely afflicts more people than prior literature suggests given that review of that literature shows patients more in line with Renal Medullary Carcinoma rather than Collecting Duct Carcinoma. 3 year overall survival of RMC is 3%. Upfront chemotherapy then surgery is the suggested treatment. Response rate to platinum based chemotherapies, gemcitabine, doxorubicin is 29%.
Interview with Herman Connor: youtu.be/w5zLOZE-Goc
Audio version of this podcast available at https://anchor.fm/chubbyemu/episodes/A-Sickle-Cell-Caused-Vasoocclusion--This-Is-What-Happened-To-The-Kidney-Medulla-e1646ln
Tweet Dr Msaouel: twitter.com/pavlosmsaouel
IG me: instagram.com/hemereview
Tweet me: twitter.com/hemereview
Thank you Dr Nizar Tannir, Dr Pavlos Msaouel, Cora and Herman Connor, and Dr Loren Stagg
Production Assistant: Nick Brown
Music by @Lifeformed ► lifeformed.bandcamp.com
Some images courtesy Getty Images
Renal Medullary Carcinoma is a sickle cell related kidney malignancy that is usually diagnosed in young patients (median age at diagnosis 28 years old). It is considered a rare malignancy but likely afflicts more people than prior literature suggests given that review of that literature shows patients more in line with Renal Medullary Carcinoma rather than Collecting Duct Carcinoma. 3 year overall survival of RMC is 3%. Upfront chemotherapy then surgery is the suggested treatment. Response rate to platinum based chemotherapies, gemcitabine, doxorubicin is 29%.
References:
Renal medullary carcinoma. The seventh sickle cell nephropathy. Am J Surg Pathol. 1995 Jan;19(1):1-11. pubmed.ncbi.nlm.nih.gov/7528470
A Model Linking Sickle Cell Hemoglobinopathies and SMARCB1 Loss in Renal Medullary Carcinoma. Clin Cancer Res. 2018 May 1;24(9):2044-2049. pubmed.ncbi.nlm.nih.gov/29440190
Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma. Clin Genitourin Cancer. 2019 Feb;17(1):1-6. pubmed.ncbi.nlm.nih.gov/30287223
Five decades of urologic pathology: the accelerating expansion of knowledge in renal cell neoplasia. Hum Pathol. 2020 Jan;95:24-45. pubmed.ncbi.nlm.nih.gov/31655169
GG Malouf, NM Tannir, P Rao, P Msaouel. Renal Medullary Carcinoma in Rare Kidney Tumors.
Comprehensive Molecular Characterization Identifies Distinct Genomic and Immune Hallmarks of Renal Medullary Carcinoma. Cancer Cell. 2020 May 11;37(5):720-734.e13. pubmed.ncbi.nlm.nih.gov/32359397
The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. pubmed.ncbi.nlm.nih.gov/10591208
High-intensity exercise is a risk factor for renal medullary carcinoma in individuals with sickle cell trait. Preprint.
Atypical carcinoma of kidney originating from collecting duct epithelium. Urology. 1982 Jan;19(1):89-92. pubmed.ncbi.nlm.nih.gov/7058597
Genes affecting the regulation of SUC2 gene expression by glucose repression in Saccharomyces cerevisiae. Genetics. 1984 Dec;108(4):845-58. pubmed.ncbi.nlm.nih.gov/6392017
Purification and biochemical heterogeneity of the mammalian SWI-SNF complex. EMBO J. 1996 Oct 1; 15(19): 5370–5382. ncbi.nlm.nih.gov/pmc/articles/PMC452280
Dr Bora Lim is a breast specialist, Associate Professor of Medicine, Director of Translational Research, and Associate Director for Clinical Science at Baylor College of Medicine
She can be reached on Twitter at twitter.com/naborala
Audio version of this episode: https://anchor.fm/chubbyemu/episodes/On-Breast-Malignancy-and-Military-Burn-Pit-Exposure-e136rjc
Timestamps:
0:00 Introduction
0:29 What is Breast Malignancy?
1:39 How does Breast Malignancy develop?
3:45 What are the risk factors for Breast Malignancy?
6:46 Brief on industrial chemicals
7:14 On burning waste
8:05 About burn pits
9:11 Burn pits as a likely health hazard
10:32 Dr Lim's veteran patient with stage 3 disease
11:46 Why is breast malignancy different?
14:51 Survival difference between Stage 2 and Stage 4
17:09 What is HR+ / HER2- disease?
19:18 What is ovarian suppression / ablation?
21:19 Do squamous and basal carcinomas increase Breast Malignancy risk?
21:54 Breast augmentation and risk of malignancy
22:16 What happens when Breast Malignancy mutates?
22:59 What happens when the malignancy spreads?
25:33 What can a veteran do if they've been exposed to burn pits?
26:56 New revelations and research on bone metastases
29:10 What can researchers do to establish a stronger link of burn pit exposure with malignancies?
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Production Assistant: Nick Brown
A Marine Inhaled Burning Garbage Fumes While Deployed. This Is What Happened To Her Organs.
Featuring: Dr Sonal Jagasia
Patient GG depicted by @MerryRoseHowley
Additional patient depictions by @JustinWhangYt
Video with @JustinWhangYt : youtu.be/QKIobyk6Isc
Audio version of this podcast: https://anchor.fm/chubbyemu
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Dextromethorphan is an over the counter cough medicine. It is for coughs. Misuse of it can cause life threatening side effects.
Thumbnail case courtesy of Dr Derek Smith, Radiopaedia.org, rID: 53692
References:
Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review. pubmed.ncbi.nlm.nih.gov/21175434
Case of Serotonin Syndrome Initially Presenting as Diffuse Body Pain. ncbi.nlm.nih.gov/pmc/articles/PMC6196581
Serotonin Syndrome. ncbi.nlm.nih.gov/pmc/articles/PMC3865832
Bromism: An overlooked and elusive toxidrome from chronic dextromethorphan misuse. pubmed.ncbi.nlm.nih.gov/31864868
Dextromethorphan-induced serotonin syndrome. pubmed.ncbi.nlm.nih.gov/19238739
Cognitive Deterioration from Long-Term Misuse of Dextromethorphan:A Case Report. ncbi.nlm.nih.gov/pmc/articles/PMC1188627
Pediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications. pubmed.ncbi.nlm.nih.gov/19101060
"DXM": a new drug of. pubmed.ncbi.nlm.nih.gov/9624331
Audio version: https://anchor.fm/chubbyemu/episodes/Hepatitis-From-Possibly-Contaminated-Alkaline-Water-euogm7
Statement from water company CEO: youtube.com/watch?v=faCsru9Ctgk
@InsideEdition video about this case: youtube.com/watch?v=lmEpmyc7g9Y
Local News talking about the water: youtube.com/watch?v=oGQJcnlk5ag
On March 13, the FDA was alerted to five cases of acute non-viral hepatitis (resulting in acute liver failure) in infants and children that occurred in November 2020 with an unknown cause reported to the Southern Nevada Health District. All five patients had been hospitalized but have since recovered. All patients were reported to have consumed “Real Water” brand alkaline water. These patients came from four different households. Five additional people, two adults and three children, from two of the four households were reported to have experienced other symptoms as well. Less severe symptoms included fever, vomiting, nausea, loss of appetite, and fatigue.
@HemeReview Audio-only episode A Grandma Collapsed From Abdominal Pain. This Is What Happened To Her Colon: https://anchor.fm/chubbyemu/episodes/A-Grandma-Collapsed-From-Abdominal-Pain--This-Is-What-Happened-To-Her-Colon-eu9rol
Psyllium husk fiber supplement can be part of a healthy diet, but it must be taken correctly. It has been shown to lower cholesterol levels to an extent, but is best in combination with a proper diet. Always take care to mix psyllium husk with more than enough water. It can become thick and cause problems if it isn't.
Audio podcast: https://anchor.fm/chubbyemu
Tweet me: twitter.com/hemereview
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References:
Potential Benefits of Dietary Fibre Intervention in Inflammatory Bowel Disease ncbi.nlm.nih.gov/pmc/articles/PMC4926452
Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia academic.oup.com/ajcn/article/70/4/466/4729069
Anaphylaxis following psyllium ingestion pubmed.ncbi.nlm.nih.gov/6736485
Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia academic.oup.com/ajcn/article/71/6/1433/4729388
Jill's Blog: throughthevalley.ca
The White Ribbon Project: twitter.com/TheWRP4LC
LUNGevity Foundation: lungevity.org
GO2 Foundation: go2foundation.org
Lung Cancer Canada: lungcancercanada.ca
Lung Foundation Australia: https://lungfoundation.com.au
Lung Cancer Europe (LUCe): https://www.lungcancereurope.eu
Tweet me: twitter.com/hemereview
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Main channel: @chubbyemu
@East-Bound Interview: youtu.be/o15HCjtSkug
@chubbyemu video on this case: youtu.be/ChPeG19qKUo
@HemeReview Podcast version: https://anchor.fm/chubbyemu
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. 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. pubmed.ncbi.nlm.nih.gov/21739343
Ambient temperature and mortality from unintentional . JAMA. 1998 Jun 10;279(22):1795-800. pubmed.ncbi.nlm.nih.gov/9628710
Dinitrophenol as a Medicine. Cells. 2019 Mar; 8(3): 280. 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. 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. pubmed.ncbi.nlm.nih.gov/30573533
The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431-44. 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. 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. 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. 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. pubmed.ncbi.nlm.nih.gov/17389084
Uncouplers of oxidative phosphorylation. Environ Health Perspect. 1990 Jul;87:213-8. pubmed.ncbi.nlm.nih.gov/2176586
Texas Woman Charged with Selling Misbranded
fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug
@chubbyemu video of this case: youtube.com/watch?v=ChPeG19qKUo
Christopher's recount of his case: youtube.com/watch?v=7BpymtR2vpA
Audio podcast for Heme Review: https://anchor.fm/chubbyemu
Tweet me: twitter.com/hemereview
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Timestamps:
0:00 - Introduction
0:30 - Can you tell me about yourself?
1:21 - How did you get into lifting weights?
3:14 - Bernard talking about his high school experience
4:12 - What was your relationship like with the gym?
5:48 - How did things change in Christopher's life at the end of high school?
8:17 - Other people's perception of weight
9:24 - Christopher describing long time girlfriend cheating on him
10:32 - People judging others based on weight
14:45 - How did you get back in to fitness during college?
17:54 - Weight loss plateau
20:54 - Weight loss supplements
24:46 - Transition from supplements to harder weight loss chemicals
31:04 - What is clenbuterol like?
33:40 - How did you come across DNP?
35:41 - What is being on DNP like?
40:00 - How long did you take DNP for?
44:58 - What do you remember from day of accident?
50:19 - Tales from the emergency room, September 3 2015
51:10 - Waking up in the ICU
55:25 - How did the accident change your relationship with the gym?
57:54 - What would you tell someone thinking of taking DNP today?
2,4-Dinitrophenol (DNP) is a chemical that is not approved for weight loss. 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.
References:
Role of dantrolene in dinitrophenol (DNP) : A continuing question? Am J Emerg Med. 2019 Jun;37(6):1216.e1-1216.e2. 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. pubmed.ncbi.nlm.nih.gov/21739343
Ambient temperature and mortality from unintentional . JAMA. 1998 Jun 10;279(22):1795-800. pubmed.ncbi.nlm.nih.gov/9628710
Beware the yellow slimming pill: fatal 2,4-dinitrophenol. BMJ Case Rep. 2016 Apr 4;2016. 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. pubmed.ncbi.nlm.nih.gov/30573533
The effect of 2,4-dinitrophenol on adipose-tissue metabolism. Biochem J. 1969 Feb;111(4):431-44. 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. 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. 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. 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. pubmed.ncbi.nlm.nih.gov/17389084
Uncouplers of oxidative phosphorylation. Environ Health Perspect. 1990 Jul;87:213-8. pubmed.ncbi.nlm.nih.gov/2176586
Texas Woman Charged with Selling Misbranded
fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug
@chubbyemu version youtu.be/qg76qIZ4BQ8
Based on N Engl J Med 2020; 383:1263-1275. Link below.
Audio-only version: https://anchor.fm/chubbyemu
TikTokers Taking Benadryl ► youtu.be/ZNA_NtcutYY
Bitcoin Miner Heatstroke ► youtu.be/QSXzRWiuvxE
A Bitcoin Miner Heatstroked In His Sleep ► youtu.be/QSXzRWiuvxE
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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.
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 54-Year-Old Man with Sudden Cardiac Arrest. N Engl J Med 2020; 383:1263-1275. nejm.org/doi/full/10.1056/NEJMcpc2002420
The Pharmacological Activities of Glycyrrhizinic Acid (“Glycyrrhizin”) and Glycyrrhetinic Acid. Sweeteners. 2018 : 245–261. ncbi.nlm.nih.gov/pmc/articles/PMC7123798
Sustained Leukocyte Count during Rising Cortisol Level. Acta Haematologica 118(2):73-6. researchgate.net/publication/6298458
nobelprize.org/prizes/medicine/1964/bloch/lecture
Licorice-Induced Hypermineralocorticoidism. N Engl J Med 1991; 325:1223-1227. 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.
Patient JC portrayed by Jacqueline Conley
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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.
@chubbyemu video of this case ▶️ youtu.be/fr8bp8a2QS4
The Body After Drinking A Snowglobe ▶️ youtu.be/elzijduKNS8
The Body After 2 Gallons Coffee In 3 Hours ▶️ youtu.be/rn-WLpa_nyQ
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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: 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.
A Man Drank 2 Liters Moonshine In 2 Hours. This Is what Happened To His Brain: youtu.be/4DQUrg0Yhu4
The Body After Drinking 2 Gallons Coffee In 3 Hours: youtube.com/watch?v=rn-WLpa_nyQ&list=PLAHeV2H_YiGUYhHOF4wRMCuqBIJvrnWqS&index=6&t=1s
All Heme Review episodes (playlist): youtube.com/playlist?list=PLAHeV2H_YiGUYhHOF4wRMCuqBIJvrnWqS
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Additional photos courtesy Radiopaedia.org, and Wellcome Collection.
Pathology slides courtesy BMJ Case Reports, September 12 2019
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. pubmed.ncbi.nlm.nih.gov/1996809
Antidotes OH that form toxic metabolites. Br J Clin Pharmacol. 2016 Mar; 81(3): 505–515. ncbi.nlm.nih.gov/pmc/articles/PMC4767193
Toxic Alcohols. N Engl J Med 2018; 378:270-280. nejm.org/doi/full/10.1056/NEJMra1615295
Ethylene glycol ingestion masked by concomitant ethanol ingestion. Case Reports 2012;2012:bcr1220115326. 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. 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. 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. nejm.org/doi/full/10.1056/NEJMcpc1410940
Integration of Acid-Base And Electrolyte Disorders. N Engl J Med 2014; 371:1821-1831. nejm.org/doi/full/10.1056/NEJMra1215672
Calcium Kidney Stones. N Engl J Med 2010; 363:954-963. nejm.org/doi/full/10.1056/NEJMcp1001011
@chubbyemu case report video ► youtu.be/wj_AOzSSDMM
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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. 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.
The Farmer Who Removed His Melanoma With A Pocket Knife ▶️youtu.be/bxGS07U-B98
The Truth About The Hydroxychloroquine Study ▶️ youtu.be/smI60BngTns
Chinese Doctors Explain▶️youtu.be/b4zely3ofBk
Audio version of Heme👏Review👏Podcast ▶️https://anchor.fm/chubbyemu
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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. 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. 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. nytimes.com/2010/09/19/health/research/19trial.html
Audio version of Heme👏Review👏Podcast ▶️https://anchor.fm/chubbyemu
Some music by @Lifeformed check out his music at his Bandcamp ▶️lifeformed.bandcamp.com
Other music inspired by Bobby Prince
References:
[0] Melanoma brain metastases: current areas of investigation and future directions. Cancer J. 2017 Jan-Feb; 23(1): 68–74. ncbi.nlm.nih.gov/pmc/articles/PMC5300745
[1] The metastatic cycle: metastatic niches and cancer cell dissemination. J Dtsch Dermatol Ges. 2014 Nov;12(11):1012-9. ncbi.nlm.nih.gov/pubmed/25307562
[2] BRAF Targets in Melanoma: Biological Mechanisms, Resistance, and Drug Discovery. Humana Press. 2015.
[3] Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature2002;417:949-954. ncbi.nlm.nih.gov/pubmed/12068308?dopt=Abstract
[4] MAP kinase pathways: the first twenty years. Biochim Biophys Acta. 2007 Aug;1773(8):1150-60. Epub 2006 Nov 15. ncbi.nlm.nih.gov/pmc/articles/PMC2043147
[5] Transport Phenomena. Bird, Stewart, Lightfoot, 2nd Ed.
#melanoma #oncology
Heme Review Podcast (full audio) ▶️https://anchor.fm/chubbyemu
Understanding COVID-19 From Cases Described By Doctors In China
▶️youtube.com/watch?v=b4zely3ofBk
Video by @chubbyemu
What (Hydroxy)chloroquine Does To The Body ▶️youtube.com/watch?v=ILowf7Tw7QY
A Student Ate 5 Day Old Pasta For Lunch. This Is How His Liver Shut Down ▶️youtube.com/watch?v=5ujTYLV2Qo4
A Man Drank 1 Bottle Rubbing Alcohol For COVID-19. This Is What Happened To His Brain ▶️youtu.be/BMSgoppbXiU
Music by @Lifeformed
Papers described in show:
- Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open- label non-randomized clinical trial. Gautret et. al. (Google Doc: drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view, version as preprint submission: sciencedirect.com/science/article/pii/S0924857920300996)
- Statistical review of Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. zenodo.org/record/3724167#.Xn7LRy2ZPAy
- White NJ. The treatment of malaria. N Engl J Med. 1996;335(11):800.
- Warhurst DC et. al. Hydroxychloroquine is much less active than chloroquine against chloroquine-resistant Plasmodium falciparum, in agreement with its physicochemical properties. J Antimicrob Chemother. 2003;52(2):188. Epub 2003 Jul 1.
- Metal Ionophores- An Emerging Class of Anticancer Drugs. iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.253
- Chloroquine is a Zinc Ionophore. ncbi.nlm.nih.gov/pmc/articles/PMC4182877/#pone.0109180-Ding1
- Treatment of Severe Chloroquine Poisoning. ncbi.nlm.nih.gov/pubmed/15837026
#coronavirus #COVID19 #sarscov2
To hear the audio as a podcast: https://anchor.fm/chubbyemu
Guest Appearance: Dr. Joe Akin, PhD, Immunologist alumnus from Harvard Medical school, of refigure.org
Please check out refigure.org/: Save and organize journal figures in one-click. (not sponsored)
Cross-reactivity of anti-SARS coronavirus antibodies to 2019 coronavirus: refigure.org/collections/item/47e25c50-51e1-11ea-80e3-85045318a762
Music by Lifeformed. Please check out his music at his Bandcamp: lifeformed.bandcamp.com
Additional music inspired by Robert Prince
COVID-19 Disease (Playlist) ► youtube.com/playlist?list=PL26HeTCO57qcOqYV6-5ZB9xleo_PaHxi4
We NEED More Testing Kits! | Coronavirus Front Line
(Doctor Mike) ► youtube.com/watch?v=DfMl6W6N7-A
COVID-19 Mutation and Evolution (Dr. John Campbell) ► youtube.com/watch?v=FYPZHA-UjUY
3 COVID-19 Cases Described By Doctors In China ► youtu.be/Q0A0LyMru3I
How Coronavirus Kills: Acute Respiratory Distress Syndrome (ARDS) & Treatment (Medcram) ► youtube.com/watch?v=okg7uq_HrhQ
Papers described in show:
Clinical Course And Outcomes Of Critically Ill Patients With SARS-CoV-2 Pneumonia In Wuhan, China: a single-centered, retrospective, observational study. Lancet. doi.org/10.1016/S2213-2600(20)30079-5
Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal Of Medicine. doi.org/10.1056/NEJMoa2002032
Early Transmission Dynamics in Wuhan, China, Of Novel Coronavirus-Infected Pneumonia. New England Journal Of Medicine. doi.org/10.1056/NEJMoa2001316
A Novel Coronavirus from Patients With Pneumonia in China, 2019. New England Journal Of Medicine. doi.org/10.1056/NEJMoa2001017
#novelcoronavirus #COVID19 #sarscov2


