Renal Medullary Carcinoma: A Kidney Cancer Associated with Sickle Cell Trait and Disease

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/

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.

​ @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

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/

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/

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/

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.

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

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/

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/