エピソード
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Dr Pavlos Msaouel: https://faculty.mdanderson.org/profiles/pavlos_msaouel.html0:00 Pretext and context MD Anderson Cancer Center1:42 The Early Experiences That Shaped Dr Msaouel3:39 The System of Cancer Research In the United States5:25 FDA Drug Approvals and Special Designations For Oncology11:09 A trade-off in our current system12:35 Whoops 😞 I misspoke 14:35 Randomized trials are not supposed to be representative of a population18:10 Inference for the treatment of Katie Coleman (metastatic oncocytoma)25:12 It is much more valuable to refute hypotheses than to confirm them28:05 All Models Are Wrong, But Some Are Useful30:05 Recasting the Bias-Variance Trade-off as the Patient Relevance-Robustness Trade-off33:38 High Relevance, Low Robustness: Subjective Bayes34:46 High Robustness, Low Relevance: Pure Randomization41:47 Signal To Noise Ratio45:49 The Big Data Paradox53:41 How the Big Data Paradox fits in with Katie Coleman's case54:33 How the Big Data Paradox fits in with other branches of medicine57:54 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 Iceberg01:07:03 Why the ideas coming from MD Anderson are coming from MD Anderson01:09:39 Where you can find Dr MsaouelDr Msaouel: https://twitter.com/PavlosMsaouelHeme Review: https://twitter.com/HemeReview
Produced by @chubbyemu Production Assistant: Nick BrownSecret channel: @BigEmus Cancer Patient Speaks With Her Oncologist ► https://youtu.be/Nddft_nc3YcA Woman Had A Headache Lasting 3 Days (Katie's case) ► https://www.youtu.be/i9fLEvgZzREReferences:Stephen Senn. Statistical Issues in Drug Development.Why representativeness should be avoided. https://academic.oup.com/ije/article/42/4/1012/656034Commentary: Representativeness is usually not necessary and often should be avoided. https://academic.oup.com/ije/article/42/4/1018/658638Impervious to Randomness: Confounding and Selection Biases in Randomized Clinical Trials. https://www.tandfonline.com/doi/full/10.1080/07357907.2021.1974030A Causal Framework for Making Individualized Treatment Decisions in Oncology. https://www.mdpi.com/2072-6694/14/16/3923Causal Diagram Techniques for Urologic Oncology Research. https://www.sciencedirect.com/science/article/pii/S1558767320301932Causal inference and the data-fusion problem.https://www.pnas.org/doi/10.1073/pnas.1510507113Causal 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.pdfThere is Individualized Treatment. Why Not Individualized Inference? https://arxiv.org/abs/1510.08539Unrepresentative big surveys significantly overestimated US vaccine uptake. https://www.nature.com/articles/s41586-021-04198-4Unrepresentative Big Surveys Significantly Overestimate US Uptake https://arxiv.org/pdf/2106.05818.pdfStatistical Modeling: The Three Cultures. https://hdsr.mitpress.mit.edu/pub/uo4hjcx6/release/1How “centaur AI” will radically reshape the future of healthcare. https://bigthink.com/health/how-centaur-ai-will-radically-reshape-the-future-of-healthcare/
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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.
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エピソードを見逃しましたか？
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@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
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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/
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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/
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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/
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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.
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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
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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/
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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/
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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/
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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.
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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
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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/
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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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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
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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
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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.
Tweet me: https://www.twitter.com/hemereview
IG me: https://www.instagram.com/hemereview
FB me: https://www.facebook.com/hemereview
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/
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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/
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MECHANISMS OF DINITROPHENOL TOXICITY. Simon E.W. Biological Reviews. Vol 28. (4). Nov 1953.
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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/
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Texas Woman Charged with Selling Misbranded
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/press-releases/texas-woman-charged-selling-misbranded-drug
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Based on N Engl J Med 2020; 383:1263-1275. https://www.nejm.org/doi/full/10.1056/NEJMcpc2002420
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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.
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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.
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The Body After 2 Gallons Coffee In 3 Hours ▶️ https://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: 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.
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