Heme Review
By Chubbyemu
Heme ReviewMar 28, 2020
The More Data You Have, The Further You Are From The Truth- Big Data Paradox in Medicine
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/
The Weird Time When Energy Drinks Fixed My Insomnia
Mug is here 😳 ► https://crowdmade.com/collections/chubbyemu
@chubbyemu energy drink video ► https://youtu.be/tAtaIZD0Ebs
A Student Ate Only Chips And Fries For 10 Years ► https://youtu.be/VINtwoyaF_8
A Mom Ate 5 Day Old Sushi 🍣 ► https://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.
Venomous Spider Bite
@chubbyemu video: https://youtu.be/xtVvtsPgfew
Heme Review Podcast: https://anchor.fm/chubbyemu
Behind the scenes channel: @BigEmus
Music by @Lifeformed ► https://lifeformed.bandcamp.com
All Heme Review videos (playlist) ► https://www.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. https://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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1071166/
Correspondance: Bites of the Brown Recluse Spider. https://www.nejm.org/doi/full/10.1056/nejm200505123521922
Spider Bites: Part 1. https://lacerationrepair.com/wound-blog/spider-bites/
Brown Recluse Pest Management Tips for The Spider That's Not As Common As You Think. https://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. https://www.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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902007/
Acute kidney injury and dermonecrosis after Loxosceles reclusa envenomation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119339/
Bites of Brown Recluse Spiders and Suspected Necrotic Arachnidism. https://www.nejm.org/doi/full/10.1056/NEJMra041184
I Abruptly Stopped Drinking Caffeine and This Happened
Caffeine Dry Scoop: https://youtu.be/sylqJ0NEVJw
Happened while filming this video: https://youtu.be/LKNfFm0QDXQ
Music by Lifeformed: https://lifeformed.bandcamp.com
References:
The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A1 Receptor. https://www.mdpi.com/1422-0067/22/1/320
Caffeine Withdrawal. https://www.ncbi.nlm.nih.gov/books/NBK430790/
A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. https://pubmed.ncbi.nlm.nih.gov/15448977/
Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. https://pubmed.ncbi.nlm.nih.gov/20492310/
Coffee, CYP1A2 genotype, and risk of myocardial infarction. https://pubmed.ncbi.nlm.nih.gov/16522833/
The Boy Who Rubbed A Whole Tube Of BenGay In-between His Legs
In 2015, a boy rubbed an entire tube of minty pain relief cream in-between his legs, and it caused his organs to shut down. Majority of modern men I believe are familiar with this action-- you may have accidentally applied it to the area yourself, or to the eyes, where it will hurt for a time that feels like an eternity.
Chubbyemu video: https://youtu.be/Le-IKCLGT9A
Boy Drinking his mom's essential oils: https://youtu.be/TZr0nt2hxbs
References:
Salicylate Toxicity from Exposure to a Methylsalicylate-Containing Rubefacient. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786239/
Regional variation in percutaneous penetration of 14C cortisol in man. https://www.jidonline.org/article/S0022-202X(15)47268-9/pdf
Anatomy and physiology of chronic s pain https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503924/
Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. https://pubmed.ncbi.nlm.nih.gov/10634967/
ISPAD Clinical Practice Consensus Guidelines 2018: DKA and the hyperglycemic hyperosmolar state. https://pubmed.ncbi.nlm.nih.gov/29900641/
Guidance Document: Management Priorities in Salicylate Toxicity. https://www.acmt.net/_Library/Position_Drafts/Management_Priorities_in_Salicylate_Toxicity_APPROVED_03_13_13.pdf
Tox and Hound – Unconscious Uncoupling – Managing pH in Salicylate Overdoses. https://toxandhound.com/toxhound/phinasa/
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. https://toxandhound.com/toxhound/phinasa/
Counterproductive effects of sodium bicarbonate in DKA. https://pubmed.ncbi.nlm.nih.gov/8550770/
Peptic ulcer disease and non-steroidal anti-inflammatory drugs https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478398
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;147:431–41. https://pubmed.ncbi.nlm.nih.gov/9439738/
Aspirin, acetaminophen and proton transport through phospholipid bilayers and mitochondrial membranes. https://pubmed.ncbi.nlm.nih.gov/1334228/
A Woman Ate 23 Bananas After Fasting 7 Days And Had Refeeding Syndrome
Fasting can be an effective tool for weight loss. However if used inappropriately, can result in some not good situations. The patient's situation in this case isn't quite like the intermittent fasting schedules that are popular today.
Chubbyemu video: https://youtu.be/nQC_GDTNkQQ
Heme Review commentary: https://youtu.be/tWlvWYGztYk
Music by Lifeformed
Tweet me: https://twitter.com/hemereview
IG me: https://instagram.com/hemereview
References:
Mechanism of hypokalemia in magnesium deficiency. Huang CL, Kuo E. J Am Soc Nephrol. 2007;18:2649–2652. https://pubmed.ncbi.nlm.nih.gov/17804670/
Hypophosphatemia and Rhabdomyolysis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC371889/
A Case of Hemodynamically Unstable Sick Sinus Syndrome Secondary to Refeeding Syndrome https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148626
Review of the Refeeding Syndrome. January 2006 Nutrition in Clinical Practice 20(6):625-33.
EMCrit Refeeding Syndrome https://emcrit.org/ibcc/refeeding/
Refeeding syndrome: what it is, and how to prevent and treat it. BMJ. 2008 Jun 28; 336(7659): 1495–1498. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440847/
The Student Who Ate 5-Day Old Pasta And His Liver Shut Down
Video version of this podcast: https://youtu.be/bq1kwlGhPyE
Original Chubbyemu video: https://youtu.be/5ujTYLV2Qo4
Tweet me: https://twitter.com/hemereview
IG me: https://instagram.com/hemereview
Music by Lifeformed
References:
Fulminant Liver Failure in Association with the Emetic Toxin of Bacillus cereus. https://www.nejm.org/doi/full/10.1056/NEJM199704173361604
Sudden Death of a Young Adult Associated with Bacillus cereus Food Poisoning. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3232990/
Acute Liver Failure after Ingestion of Fried Rice Balls: A Case Series of Bacillus cereus Food Poisonings. https://doi.org/10.3390/toxins14010012
Fatal Family Outbreak of Bacillus cereus-Associated Food Poisoning. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1233987/
Bacillus cereus and its food poisoning toxins. https://pubmed.ncbi.nlm.nih.gov/9435100/
Liver Zonation – Revisiting Old Questions With New Technologies. https://www.frontiersin.org/articles/10.3389/fphys.2021.732929/full
Bacillus cereus food poisoning. https://www.nejm.org/doi/full/10.1056/NEJM197801192980306
Tox and Hound: D and Toxin-Induced Hepatic Microvesicular Steatosis https://toxandhound.com/toxhound/ff-microvesicular-steatosis/
ENCEPHALOPATHY AND FATTY DEGENERATION OF THE VISCERA. A DISEASE ENTITY IN CHILDHOOD. https://pubmed.ncbi.nlm.nih.gov/14055046/
Whatever happened to Reye’s syndrome? Did it ever really exist? https://pubmed.ncbi.nlm.nih.gov/10470768/
Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. https://pubmed.ncbi.nlm.nih.gov/22120519/
Prevalence of Alcoholic Fatty Liver Disease Among Adults in the United States, 2001-2016. https://pubmed.ncbi.nlm.nih.gov/31063562/
Goldfrank's Toxicologic Emergencies 11th ed.
Interview With A Rare Renal Medullary Carcinoma Survivor
Chubbyemu video: https://youtu.be/3E75UvmY9GA
Heme Review video on Renal Medullary Carcinoma: https://youtu.be/j7WGP6sJBLk
Herman Connor
Contact Cora Connor (Herman's sister): https://www.twitter.com/RMCAwareness
Cora Facebook: https://www.facebook.com/RMCSupport
IG me: https://www.instagram.com/hemereview
Tweet me: https://www.twitter.com/hemereview
Renal Medullary Carcinoma: A Kidney Cancer Associated with Sickle Cell Trait and Disease
Video version of this podcast: https://youtu.be/j7WGP6sJBLk
Chubbyemu video A Man Felt Pain In His Back. This Is What Happened To His Kidney. https://youtu.be/3E75UvmY9GA
References:
Renal medullary carcinoma. The seventh sickle cell nephropathy. Am J Surg Pathol. 1995 Jan;19(1):1-11. https://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. https://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. https://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. https://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. https://pubmed.ncbi.nlm.nih.gov/32359397/
The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. https://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. https://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. https://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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC452280/
On Breast Malignancy and Military Burn Pit Exposure
Video version of this podcast: https://youtu.be/B8LLf7DkR5U
Chubbyemu video of KT: https://youtu.be/LKNfFm0QDXQ
Dr Bora Lim can be reached at https://www.twitter.com/naborala
Burn pits are a waste management tool for armed forces overseas. However, the nature of waste today is different than half a century ago. The smoke, fumes, and particulate matter that have been observed emanating from these pits contain a heterogeneous variety of materials. Exact exposure levels are not known in veterans, however many of these materials are known to be linked to long term health effects and some have been classified and recognized as carcinogens via retrospective analysis in humans and laboratory experiments. The particulate matter produced from these burn pits can also deposit into the earth and during weather events such as dust storms, can circulate the particles to local inhabitants, potentially causing health effects for them, years later. Recognizing these long term health effects will enable people to not make these mistakes again, and to help those who have been exposed.
References:
VA Burn Pit Registry: https://veteran.mobilehealth.va.gov/AHBurnPitRegistry
Source Apportionment of Airborne Dioxins, Furans and Polycyclic Aromatic Hydrocarbons at A U.S. Forward Operating Air Base During Iraq https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978146/
Long-Term Health Consequences of Exposure to Burn Pits in Iraq and Afghanistan https://www.nap.edu/catalog/13209/long-term-health-consequences-of-exposure-to-burn-pits-in-iraq-and-afghanistan
Polychlorinated Dibenzo-para-Dioxins and Polychlorinated Dibenzofurans. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 69. https://publications.iarc.fr/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Polychlorinated-Dibenzo--Em-Para-Em--Dioxins-And-Polychlorinated-Dibenzofurans-1997
Dioxin Revisited: Developments Since the 1997 IARC Classification of Dioxin as a Human Carcinogen https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1247514
Serum dioxin concentrations and breast ca risk in the Seveso Women's Health Study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240906/
Detection of hyperdiploidy and chromosome breakage in interphase human lymphocytes following exposure to the benzene metabolite hydroquinone using multicolor fluorescence in situ hybridization with DNA probes. https://pubmed.ncbi.nlm.nih.gov/7517507/
A Discussion On Over-The-Counter Cough Syrup Misuse
Video version of this podcast: https://youtu.be/oP_mJmWrfTQ
Chubbyemu video of this case: https://www.youtube.com/watch?v=WPxb2IG9MOk
Featuring: Dr Sonal Jagasia, MD, MPH. Psychiatrist in private practice.
Tweet me: https://www.twitter.com/hemereview
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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.
References:
Dextromethorphan, chlorphenamine and serotonin toxicity: case report and systematic literature review. https://pubmed.ncbi.nlm.nih.gov/21175434/
Case of Serotonin Syndrome Initially Presenting as Diffuse Body Pain. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196581/
Serotonin Syndrome. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832
Bromism: An overlooked and elusive toxidrome from chronic dextromethorphan misuse. https://pubmed.ncbi.nlm.nih.gov/31864868/
Dextromethorphan-induced serotonin syndrome. https://pubmed.ncbi.nlm.nih.gov/19238739/
Cognitive Deterioration from Long-Term Misuse of Dextromethorphan:A Case Report. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1188627/
Pediatric Fatalities Associated With Over the Counter (Nonprescription) Cough and Cold Medications. https://pubmed.ncbi.nlm.nih.gov/19101060/
"DXM": a new drug of. https://pubmed.ncbi.nlm.nih.gov/9624331/
Hepatitis From Possibly Contaminated Alkaline Water
This episode is up to date as of 11 April 2021
Video version of this podcast: https://youtu.be/dsZzKzGdgTo
Statement from water company CEO: https://www.youtube.com/watch?v=faCsru9Ctgk
Inside Edition video about this case: https://www.youtube.com/watch?v=lmEpmyc7g9Y
Local News talking about the water: https://www.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.
A Grandma Collapsed From Abdominal Pain. This Is What Happened To Her Colon.
Chubbyemu video: https://www.youtube.com/watch?v=1MggKIfEld4
Heme Review video: https://www.youtube.com/watch?v=mPHXldh4_H4
Tweet me: https://www.twitter.com/hemereview
IG me: https://www.instagram.com/hemereview
FB me: https://www.facebook.com/hemereview
Chubbyemu YouTube channel: https://www.youtube.com/channel/UCKOvOaJv4GK-oDqx-sj7VVg
Heme Review YouTube channel: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA
References:
Potential Benefits of Dietary Fibre Intervention in Inflammatory Bowel Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926452/
Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia https://academic.oup.com/ajcn/article/70/4/466/4729069
Anaphylaxis following psyllium ingestion https://pubmed.ncbi.nlm.nih.gov/6736485/
Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia https://academic.oup.com/ajcn/article/71/6/1433/4729388
Potential Benefits of Dietary Fibre Intervention in Inflammatory Bowel Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4926452/
Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia https://academic.oup.com/ajcn/article/70/4/466/4729069
Anaphylaxis following psyllium ingestion https://pubmed.ncbi.nlm.nih.gov/6736485/
Long-term cholesterol-lowering effects of psyllium as an adjunct to diet therapy in the treatment of hypercholesterolemia https://academic.oup.com/ajcn/article/71/6/1433/4729388
Small Bowel Obstruction Secondary to a Metamucil Bezoar: Case Report and Review of the Literature https://pubmed.ncbi.nlm.nih.gov/29085697/
The role of dietary fibre in the human colon https://pubmed.ncbi.nlm.nih.gov/6257366/
Intestinal obstruction caused by a laxative (Psyllium): A case report and review of the literature https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197948/
Interview With A Stage 4 Lung Cancer Survivor (Jill Hamer-Wilson)
Video version of this interview: https://youtu.be/oLe9UdL-qIk
Jill's Blog: https://throughthevalley.ca
White Ribbon Project: https://twitter.com/TheWRP4LC
LUNGevity Foundation: https://lungevity.org
GO2 Foundation: https://go2foundation.org
Lung Cancer Canada: https://www.lungcancercanada.ca
Lung Foundation Australia: https://lungfoundation.com.au
Lung Cancer Europe (LUCe): https://www.lungcancereurope.eu
Tweet me: https://www.twitter.com/hemereview
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Some Chubbyemu Videos That I Might Not Be Able To Make
Please note the CONTENT WARNING at the beginning-- there's a reason I can't make the videos as described in this episode. They may surface in a different form at some time in the future.
Heme Review YouTube: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA
Tweet me: https://www.twitter.com/hemereview
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BONUS- Interview With A Rare Dinitrophenol Accident Survivor (DNP For Weight Loss)
Video of this interview: https://youtu.be/o15HCjtSkug
Chubbyemu video https://youtu.be/ChPeG19qKUo
Christopher's recount of his case: https://youtu.be/7BpymtR2vpA
Tweet me: https://www.twitter.com/hemereview
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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. 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/
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
A Brief Discussion Of Dinitrophenol In The Setting Of Weight Loss
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
Based on N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420
Video version of this podcast: https://youtu.be/8lGmvFkAMOU
Chubbyemu video of this case: https://youtu.be/qg76qIZ4BQ8
Laxative Brownie video from 2017: https://youtu.be/TMy0vJfKvzI
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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
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)
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
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.
Heme Review YouTube Channel: https://www.youtube.com/channel/UCNSoNc9s67nfOGlCXSu5VsA
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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
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)
Video version of episode: https://www.youtube.com/watch?v=elzijduKNS8
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
Max recommended amount of caffeine per day is 400mg.
@Chubbyemu case report video ► https://youtu.be/wj_AOzSSDMM
Video version of this episode ► https://youtu.be/rn-WLpa_nyQ
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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
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Video version of this video: https://youtu.be/iVt5BpoTHYg
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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
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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
Thoughts About Hydroxychloroquine For COVID19 (March 2020)
This episode was recorded on and is current up to Friday March 27 2020.
Support this podcast! https://anchor.fm/chubbyemu/support
Video version of this podcast: https://youtu.be/smI60BngTns
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: https://drive.google.com/file/d/186Bel9RqfsmEx55FDum4xY_IlWSHnGbj/view, version as preprint submission: https://www.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. https://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. https://iubmb.onlinelibrary.wiley.com/doi/full/10.1002/iub.253
- Chloroquine is a Zinc Ionophore. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877/#pone.0109180-Ding1
- Treatment of Severe Chloroquine Poisoning. https://www.ncbi.nlm.nih.gov/pubmed/15837026
Music by Lifeformed. Please check out his music at his Bandcamp: https://lifeformed.bandcamp.com
Video by Chubbyemu:
A Man Drank 1 Bottle Rubbing Alcohol For COVID-19. This Is What Happened To His Brain: https://youtu.be/BMSgoppbXiU
Explaining COVID19 From Cases Described By Doctors In China
This episode is current up to Friday March 6. Guest Appearance: Dr. Joe Akin, PhD, Immunologist alumnus from Harvard Medical school, of https://refigure.org.
Support this podcast! https://anchor.fm/chubbyemu/support
Video version of this episode: https://youtu.be/b4zely3ofBk
Please check out https://refigure.org: Save and organize journal figures in one-click. (not sponsored)
Music by Lifeformed. Please check out his music at his Bandcamp: https://lifeformed.bandcamp.com
Additional music inspired by Robert Prince
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. https://doi.org/10.1016/S2213-2600(20)30079-5
Clinical Characteristics of Coronavirus Disease 2019 in China. New England Journal Of Medicine. https://doi.org/10.1056/NEJMoa2002032
Early Transmission Dynamics in Wuhan, China, Of Novel Coronavirus-Infected Pneumonia. New England Journal Of Medicine. https://doi.org/10.1056/NEJMoa2001316
A Novel Coronavirus from Patients With Pneumonia in China, 2019. New England Journal Of Medicine. https://doi.org/10.1056/NEJMoa2001017
Video by Chubbyemu:
3 COVID19 Cases As Described By Doctors In China: https://youtu.be/Q0A0LyMru3I