Physician's Weekly Podcast

This week, we have two top-tier guests explaining some pretty remarkable breakthroughs published this summer in their respective fields of MS and dermatology, respectively. 

Sergio Baranzini, PhD (UCSF), discusses recently published research on a genetic breakthrough in understanding MS progression. Dr. Baranzini’s research involves large analyses of samples from patients with MS to characterize the activity of genes during 1) different stages of the disease (eg, remission vs. relapse), 2) differential response to treatment (eg, good responders vs. poor responders), and 3) disease progression (eg, benign vs. severe). 

Also, Peter Marinkovich, MD (Stanford) explains a genetic breakthrough in the treatment of the severe skin condition recessive dystrophic epidermolysis bullosa. We learn about this condition and how Dr. Marinkovich’s team has developed an effective gene therapy that has shown very promising results in their recently published clinical trial.  

 Enjoy Listening!

 Additional reading

International Multiple Sclerosis Genetics Consortium; MultipleMS Consortium. Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature. 2023 Jul;619(7969):323-331

Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nat Med. 2022 Apr;28(4):780-788. 

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Samir Mitragotri, PhD (The Mitragotri lab, Harvard) discusses a novel breakthrough his lab recently published in which an engineered particle referred to as a “backpack” can robustly adhere to macrophage surfaces and regulate cellular phenotypes in vivo. Understanding how these approaches work is not only interesting, it is a refreshing and innovative approach to drug delivery we will be seeing more of soon. 

 Also, Pancreatic Cancer Action (PCA) founder and pancreatic cancer survivor Ali Stunt reviews life-changing interventions taking place to diagnose pancreatic cancer earlier and improve survival. PCA has succeeded in campaigning for many life-changing interventions in terms of direct referrals for CT scans for general practitioners, direct referrals for pharmacists, and breaking down barriers so that the general public can better understand symptoms and risk factors. 

Enjoy Listening!

Additional reading

chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://gco.iarc.fr/today/data/factsheets/cancers/13-Pancreas-fact-sheet.pdf

https://www.mitragotrilab.seas.harvard.edu/

Kapate N, Dunne M, Kumbhojkar N, Prakash S, Wang LL, Graveline A, Park KS, Chandran Suja V, Goyal J, Clegg JR, Mitragotri S. A backpack-based myeloid cell therapy for multiple sclerosis. Proc Natl Acad Sci U S A. 2023 Apr 25;120(17):e2221535120. 

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Almost one-half of adolescents have experienced a mental health disorder, and while medications have the potential to be very effective for some, others might not respond or even experience adverse reactions as a result of their genetics. When it comes to treating children and teens in crisis, every second counts—and drug-gene testing can help doctors ensure they prescribe the right therapies from the start. Genetic tests for variants impacting drug metabolization have advanced tremendously and insights uncovered in youth can yield lifelong benefits by identifying which treatments will be effective for each patient. Joel Diamond, MD (University of Pittsburgh, 2bPrecise), unpacks how drug-gene testing can optimize behavioral health treatment pathways for young patients for their entire lives.

Also, Jennifer Brown, MD, PhD, covers what every doctor should know about recognizing chronic lymphocytic leukemia (CLL), including recent treatment developments. She discusses the meeting of the International Workshop on CLL  iwCLL that she is organizing this year in Boston; iwCLL is an international, non-profit association committed to creating progress in the management and outcome of patients with CLl world-wide.

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In the second episode of a series of in-depth conversations, Dike Drummond, MD (family physician, CEO of TheHappyMD.com), discusses the fundamental conflict underlying most physicians’ burnout and how to move forward. Dr. Drummond has coached and trained more than 40,000 doctors for over 175 organization and association clients since 2010. His Burnout Prevention MATRIX White Paper shares 235 different ways to stop physician burnout. This is a topic worthy of extensive discussion. Take the time to take care of yourself and listen to what our guest can teach you about recognizing and dealing with imminent burnout. 

Enjoy Listening!

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Nicolas Girard, MD (Curie-Montsouris Thorax Institute, Institut Curie, France), discusses lung cancer research he presented at ASCO 2023, including an advance in the understanding of this difficult-to-treat disease. Also Gregory Lip, MD (University of Liverpool, UK), reviews the most important updates to the CHEST clinical guidelines on antithrombotic therapy in arterial thrombosis and thromboembolism in COVID-19.

Enjoy listening!

Additional Reading

Tatjana Potpara et al, Antithrombotic therapy in arterial thrombosis and thromboembolism in COVID-19: An American College of Chest Physicians Expert Panel Report, Chest (2023). DOI: 10.1016/j.chest.2023.06.032

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Vignesh Arasu, MD, PhD (Kaiser Permanente Northern California Division of Research), explains his research at the intersection of medical imaging, breast cancer, and artificial intelligence. With the recently released documentary “Below the Belt” brining endometriosis into the limelight of late, we also take a deep dive into its etiology with David Redwine, MD, a retired obstetrician-gynecologist who spent his career investigating the origin of endometriosis. 

Enjoy Listening!

Additional reading

Arasu VA, Habel LA, Achacoso NS, Buist DSM, Cord JB, Esserman LJ, Hylton NM, Glymour MM, Kornak J, Kushi LH, Lewis DA, Liu VX, Lydon CM, Miglioretti DL, Navarro DA, Pu A, Shen L, Sieh W, Yoon HC, Lee C. Comparison of Mammography AI Algorithms with a Clinical Risk Model for 5-year Breast Cancer Risk Prediction: An Observational Study. Radiology. 2023 Jun;307(5):e222733. doi: 10.1148/radiol.222733. PMID: 37278627; PMCID: PMC10315521.

https://www.belowthebelt.film/

Redwine DB. Was Sampson wrong? Fertil Steril. 2002 Oct;78(4):686-93. doi: 10.1016/s0015-0282(02)03329-0. PMID: 12372441.

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Amie Zarling, PhD (Associate Professor of Clinical Psychology at Iowa State University), reviews some interesting research on developing and evaluating effective programs for hard-to-reach, under-resourced, and/or under-served populations, which primarily focus on improving family health. Also, regular contributor Dr. MedLaw discusses how, when, and why physicians should disclose their own errors. Did you know that hiding an error will underpin the independent intentional tort of fraudulent concealment and that because it is an intentional choice, it will not be covered by malpractice insurance? How about that the Statute of Limitations for fraudulent concealment is also usually three times longer than that for malpractice?

Listen to learn more!

Further reading

https://faculty.sites.iastate.edu/azarling/ 

Hudson J, Zarling A, Ungar R, Albright L, Tkatch R, Russell D, Schaeffer J, Wicker ER. Older Adults' Experiences in a Web-Based Intervention for Loneliness. Gerontol Geriatr Med. 2023 Mar 22;9:23337214231163004. doi: 10.1177/23337214231163004. PMID: 36968123; PMCID: PMC10037731.

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Welcome to Episode 101, which seems a great place to go back to basics! Regular PW podcast contributor and PW Editorial Board member Alex McDonald, MD, speaks with Francis Chu, MD, a family physician who currently serves as the program director for Kaiser Permanente San Jose (KPSJ) Family Medicine Residency, director of Graduate Medical Education at KPSJ, assistant dean of the KP Silicon Valley Regional Campus, and volunteer instructor of Family Medicine at Boston University. Drs. McDonald and Chu have a great conversation about graduate medical education and how best to use it to your advantage. 

Enjoy listening!

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This week’s episode of the PW Podcast is celebratory, in honor of our 100th episode. This has been a fantastic adventure, and we have been honored to interview more than 150 health practitioners to date, exposed to so much fantastic clinical science and expertise! We need to thank all our guests, as well as our regular contributors, Dr. Medlaw and Dr. Alex McDonald. This is an opportunity to also thank our sound guys at The Audio and the great staff at Physician’s Weekly. But we would especially like to thank you, the listeners!

To celebrate this milestone, Dr. Alex McDonald (Physician’s Weekly Editorial Board Member and family/sports medicine physician at Southern California Permanente Medical Group) and PW Podcast host Rachel Giles, MD, generated a list of their “Heroes of Medicine,” which they discuss in this episode; this list reflects their personal choices and just scrapes the surface. We would love to hear your suggestions of who was missed! 

Enjoy Listening!

Heroes of Medicine:

1. Hippocrates promoted the idea that gods did not cast illnesses
2. Edward Jenner: 1796, first vaccine à small pox
3. Watson and Crick (and Rosalind Franklin): 1953 - DNA
4. Louis Pasteur: 1864, microorganisms in the air and water
5. Alexander Fleming: 1928, antibiotics
6. Ignaz Semmelweiss: 1846, handwashing, and no one believed him!
7. Harold Varmus: open access publishing (Public Library of Science, PLoS)
8. James Lind: first clinical trial, he was a ship's surgeon in the Royal Navy. While at sea in May 1747, Lind provided some crew members with two oranges and one lemon, proving scurvy could be prevented by citrus
9. Jennifer Doudna: 2006, CRISPR gene editing
10. Mary Claire King: 1989, not for discovery of breast cancer gene but for her humanitarian work performing pro bono sequencing of children “lost” in the dictatorship of Argentina and placing them back with their families
11. Peter Ratcliffe, Bill Kaelin, Greg Semenza: 2019, Nobel prize - hypoxia signaling
12. Elizabeth Blackwell: 1849, became the first woman in America to receive an MD. She was soon joined by her younger sister, and together, the Blackwells founded the New York Infirmary for Indigent Women and Children, the first hospital staffed entirely by women.
13. Paul Farmer: with colleagues, pioneered novel, community-based treatment strategies that demonstrate the delivery of high-quality healthcare in resource-poor settings. He wrote extensively on health, human rights, and the consequences of social inequality.

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Doctor burnout is a significant and pervasive issue that can have detrimental effects on well-being, job satisfaction, and ultimately, patient care. Dike Drummond, MD, family doctor and CEO of TheHappyMD.com, discusses this important topic. Dr. Drummond is the author of the Burnout Prevention MATRIX, which shares 235 ways to stop burnout, and has coached and trained over 40,000 doctors.

Enjoy Listening!

Check out Dr. Drummond's 1st post in the new TheHappyMD@PW series! And check back monthly for more conversations with him on recognizing and addressing physician burnout.

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Patrice Forget, MD, PhD (University of Aberdeen) discusses developments in safe pain management and the best evidence-based use of opioids in the current landscape. Dr. Forget is a recognized international expert on pain management and recently published an overview on this topic in Lancet. Also, Dr. MedLaw shares her clinical and legal perspective on dealing with another doctor’s errors. Dr. MedLaw explores the issue of whether doctors who notice these errors become legally liable if they do not intervene in the event of a worsening medical situation.

Enjoy Listening!

Additional reading: 

Forget P, Hauser W. Europe has much to do to improve the quality of and access to safe pain management. Lancet. 2023;401(10389):P1651. doi:10.1016/S0140-6736(23)00669-4

Forget P. Prescribing and deprescribing opioids. Pain. 2022;163(1):1-2. doi:10.1097/j.pain.0000000000002299 

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Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com!

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The 14th-century bubonic plague killed up to half the population in Europe, the Middle East, and North Africa. It has been hypothesized that such a deadly disease may have provided a selected event for genetic variants that protect against infection. People with protective versions of certain genes would be more likely to survive and pass on those variants to future generations. Yet pinpointing such variants has been a challenge. An NIH-funded team of researchers, led by Drs. Hendrik Poinar (McMaster University) and Luis Barreiro (University of Chicago) sampled DNA from the remains of more than 500 people who died before, during, and after the Black Death, which raged in 1348 to 1349. Dr. Barreiro, explains his research, which found genetic variant enriched by the Black Death contribute to Crohn’s and other autoimmune disorders. 

There have been some big breakthroughs in the treatment of liver cancer the last 2 years, raising the question of whether non-trial populations of patients do as well as those reported in the major clinical trials. We speak with Cha Len Lee, MD (University of Toronto), about therapy with atezolizumab and bevacizumab improving recurrence-free survival in patients with hepatocellular carcinoma (HCC) following surgical resection or ablation, according to results from the phase 3 IMbrave050 clinical trial (NCT04102098). As this combination therapy is finding its way into practice, Dr. Lee performed a study to assess the efficacy, safety, and value of esophagogastroduodenoscopy with regard to this combination therapy in the real world.

Enjoy Listening!

Additional reading:

Klunk J, et al. Evolution of immune genes is associated with the Black Death. Nature. 2022 Nov;611(7935):312-319. 

Kudo M, et al. Efficacy, safety and patient reported outcomes (PROs) from the phase III IMbrave050 trial of adjuvant atezolizumab (atezo) + bevacizumab (bev) vs active surveillance in patients with hepatocellular carcinoma (HCC) at high risk of disease recurrence following resection or ablation. ASCO, June 2-6, 2023, Chicago, USA. Abstract: 4002

Hack SP, et al. Future Oncol. 2020 May;16(15):975-989. 

Finn RS, et al. N Engl J Med 2020; 382:1894-1905.

Lee C

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Gary Milechman, MD, FACC (UCSF Cardiovascular Care and Prevention Center), explains how curiosity guides his differential diagnostics approach, which he shares in teaching the nearly lost art of diagnostics. Also, Adrian Desai Boström, PhD (Karolinksa Institute, Sweden), discuses the implications of his study findings, indicating that male adolescents living in areas where bipolar disorder is diagnosed more frequently are also associated with significantly fewer suicide deaths than in patients living in areas where bipolar disorder is less prevalent.

Enjoy Listening!

Additional reading:

Andersson P, Jokinen J, Jarbin H, Lundberg J, Desai Boström AE. Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden. JAMA Psychiatry. 2023 May 24:e231390. doi: 10.1001/jamapsychiatry.2023.1390. Epub ahead of print. PMID: 37223908; PMCID: PMC10209824.

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Karsonya Wise Whitehead, PhD (Executive Director, Karson Institute for Race, Peace, and Social Justice, Communication and African & African American Studies, Loyola University Maryland and President, National Women's Studies Association), discusses the ongoing impacts of the George Floyd murder case, sharing the facts that 79% of Black parents say police violence affects their mental health and that 38% of Black people say the feel anxious when the see an officer. Also, Tracy Velázquez, MS, MPA (Senior Manager, Safety & Justice, The Pew Charitable Trusts), reviews a nationally representative survey that found only 13% of US adults know of the 988 Suicide and Crisis Lifeline and its purpose, 9 months after its launch.

Enjoy Listening!

Additional reading:

https://www.nytimes.com/interactive/2023/05/25/well/mind/black-mental-health-police-violence.html

https://www.pewtrusts.org/en/research-and-analysis/articles/2023/05/23/most-us-adults-remain-unaware-of-988-suicide-and-crisis-lifeline

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Steven Younger, MD (Sutter Health California Pacific Medical Center), talks with us about tough conversations with patients after poor outcomes, as well as the “Great Resignation” and the consequent stress on physicians due to shortages.

Also, Nader Sanai, MD (Chief Scientific Officer/Director Neurosurgical Oncologist, Ivy Brain Tumor Center), discusses the challenges facing brain cancer research and treatment and efforts to find a cure. Those with a brain cancer diagnosis quickly run out of options. Survival rates haven't risen in decades, and a new FDA-approved therapy hasn't been introduced in as long. Brain cancer has long been underfunded, compared with other cancers and relative to the number of new cases, deaths, and years of life lost. To answer this unmet need, Dr. Sanai has pioneered a phase 0 clinical trial approach for research and drug development. We hear about how tides are changing for the better with this experimental approach. 

Enjoy listening!

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Carla Perissinotto, MD, MHS (Professor of Geriatric Medicine, UCSF) frames her recently published data on social isolation and loneliness as medical issues in the context of the Surgeon General’s report stating that “loneliness in older adults is a health priority.” We then turn to a situation many doctors would not have necessarily have thought was related to them. The charges were recently dropped against Alec Baldwin in the case of the cinematographer who was killed on his movie set when a real bullet was fired instead of a blank, but charges are still pending against the armorer who loaded the gun that was given to him. Many doctors are confused about this; does it suggest that if someone assisting a doctor misinforms them about a patient or hands them a wrong medicine that liability stops with that assistant? Our regular contributor, Dr. MedLaw (board-certified radiologist and malpractice attorney) answers these and other related questions.

Enjoy listening!

Further reading

Holt-Lunstad J, Perissinotto C. Social Isolation and Loneliness as Medical Issues. N Engl J Med. 2023 Jan 19;388(3):193-195. 

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Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com!

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Dena Battle (President, KCCure), a former congressional aide who spent nearly two decades working on tax and healthcare policy—with expertise in health care reimbursement, tax treatment of benefit plans, the orphan-drug tax credit, and corporate research and development policy—discusses medical misinformation on the Internet and the mitigation of doctor-patient discord. Also, Bernard Zalc, MD, reviews a new model that may help correlate demyelination with the evolution of cognitive and motor abilities in patients with multiple sclerosis (MS). This new tool, which allows in vivo monitoring, has the potential to advance our knowledge of the link between visual disorders—one of the most common symptoms of multiple sclerosis—and associated demyelination lesions. Keep listening to learn more!

Additional reading:

Henriet E, Martin EM, Jubin P, Langui D, Mannioui A, Stankoff B, Lubetzki C, Khakhalin A, Zalc B. Monitoring recovery after CNS demyelination, a novel tool to de-risk pro-remyelinating strategies. Brain. 2023 Mar 30:awad051. 

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John Showalter, MD (CPO, Linus Health) discusses the types of cognitive care that patients want from their physicians and what physicians need to know about cognitive health as is carves out a bigger place in primary care. According to a recent survey of patient expectations, more than 80% of elderly patients are concerned about developing dementia, but their doctors are not screening for early indicators or discussing treatment and prevention. Dr. Showalter discusses this survey data and why proactive cognitive care must become the standard immediately. Also, Lydia Makaroff, PhD (CEO, Fight Bladder Cancer in the UK, and current President, World Bladder Cancer Patient Coalition), and Alex Filicevas (Executive Director, World Bladder Cancer Patient Coalition) explore obstacles to quality care in bladder cancer, as well as topline and brand new data from their global survey among patients and caregivers. Wondering why you might see a lot of bubble blowing this month? May is Bladder Cancer Awareness Month, and to draw attention to this, the world bladder cancer community, patients and physicians alike, will be blowing bubbles. 
 
Enjoy!

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Regular contributor Dr. MedLaw explains the legal doctrine “assumption of the risk,” helping answer the question “If a patient is explained the risks of medical care and agrees to the treatment, aren’t they agreeing to those risks?” Also, Cynthia Kelly, RD, CD (CEO of the Gluten Intolerance Group), discusses new understandings in gluten sensitivity and intolerance, including Celiac disease. She reviews the pathophysiology and addresses how to help patients overcome obstacles to reducing gluten intake.

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Steven Woolf, MD, MPH (Virginia Commonwealth University School of Medicine), discusses the ominous implications of the largest increase in US all-cause pediatric mortality rates in at least 50 years (up 20% in 2019-2021). A nation that begins losing its most cherished population—its children—faces a crisis like no other. Also, Sergio Giralt, MD, reviews results from the MarMMa-3 trial, which investigated the safety and efficacy of idecabtagene vicleucel for relapsed or refractory multiple myeloma. The findings were recently published in the New England Journal of Medicine. How will this change the treatment landscape for patients with multiple myeloma?

 Enjoy listening!

Additional reading:

Woolf SH, Wolf ER, Rivara FP. The New Crisis of Increasing All-Cause Mortality in US Children and Adolescents. JAMA. 2023 Mar 28;329(12):975-976. 

Rodriguez-Otero P, Ailawadhi S, Arnulf B, Patel K, Cavo M, Nooka AK, Manier S, Callander N, Costa LJ, Vij R, Bahlis NJ, Moreau P, Solomon SR, Delforge M, Berdeja J, Truppel-Hartmann A, Yang Z, Favre-Kontula L, Wu F, Piasecki J, Cook M, Giralt S. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023 Mar 16;388(11):1002-1014. 

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Want to share your medical expertise, research, or unique experience in medicine on the PW podcast? Email us at editorial@physweekly.com!

Thanks for listening!