Podcasts about Kaposi

Dr. Gary Null provides a commentary on "Universal  Healthcare"       Universal Healthcare is the Solution to a Broken Medical System Gary Null, PhD Progressive Radio Network, March 3, 2025 For over 50 years, there has been no concerted or successful effort to bring down medical costs in the American healthcare system. Nor are the federal health agencies making disease prevention a priority. Regardless whether the political left or right sponsors proposals for reform, such measures are repeatedly defeated by both parties in Congress. As a result, the nation's healthcare system remains one of the most expensive and least efficient in the developed world. For the past 30 years, medical bills contributing to personal debt regularly rank among the top three causes of personal bankruptcy. This is a reality that reflects not only the financial strain on ordinary Americans but the systemic failure of the healthcare system itself. The urgent question is: If President Trump and his administration are truly seeking to reduce the nation's $36 trillion deficit, why is there no serious effort to reform the most bloated and corrupt sector of the economy? A key obstacle is the widespread misinformation campaign that falsely claims universal health care would cost an additional $2 trillion annually and further balloon the national debt. However, a more honest assessment reveals the opposite. If the US adopted a universal single-payer system, the nation could actually save up to $20 trillion over the next 10 years rather than add to the deficit. Even with the most ambitious efforts by people like Elon Musk to rein in federal spending or optimize government efficiency, the estimated savings would only amount to $500 billion. This is only a fraction of what could be achieved through comprehensive healthcare reform alone. Healthcare is the largest single expenditure of the federal budget. A careful examination of where the $5 trillion spent annually on healthcare actually goes reveals massive systemic fraud and inefficiency. Aside from emergency medicine, which accounts for only 10-12 percent of total healthcare expenditures, the bulk of this spending does not deliver better health outcomes nor reduce trends in physical and mental illness. Applying Ockham's Razor, the principle that the simplest solution is often the best, the obvious conclusion is that America's astronomical healthcare costs are the direct result of price gouging on an unimaginable scale. For example, in most small businesses, profit margins range between 1.6 and 2.5 percent, such as in grocery retail. Yet the pharmaceutical industrial complex routinely operates on markup rates as high as 150,000 percent for many prescription drugs. The chart below highlights the astronomical gap between the retail price of some top-selling patented pharmaceutical medications and their generic equivalents. Drug Condition Patent Price (per unit) Generic Price Estimated Manufacture Cost Markup Source Insulin (Humalog) Diabetes $300 $30 $3 10,000% Rand (2021) EpiPen Allergic reactions $600 $30 $10 6,000% BMJ (2022) Daraprim Toxoplasmosis $750/pill $2 $0.50 150,000% JAMA (2019) Harvoni Hepatitis C $94,500 (12 weeks) $30,000 $200 47,000% WHO Report (2018) Lipitor Cholesterol $150 $10 $0.50 29,900% Health Affairs (2020) Xarelto Blood Thinner $450 $25 $1.50 30,000% NEJM (2020) Abilify Schizophrenia $800 (30 tablets) $15 $2 39,900% AJMC (2019) Revlimid Cancer $16,000/mo $450 $150 10,500% Kaiser Health News (2021) Humira Arthritis $2,984/dose $400 $50 5,868% Rand (2021) Sovaldi Hepatitis C $1,000/pill $10 $2 49,900% JAMA (2021) Xolair Asthma $2,400/dose $300 $50 4,800% NEJM (2020) Gleevec Leukemia $10,000/mo $350 $200 4,900% Harvard Public Health Review (2020) OxyContin Pain Relief $600 (30 tablets) $15 $0.50 119,900% BMJ (2022) Remdesivir Covid-19 $3,120 (5 doses) N/A $10 31,100% The Lancet (2020) The corruption extends far beyond price gouging. Many pharmaceutical companies convince federal health agencies to fund their basic research and drug development with taxpayer dollars. Yet when these companies bring successful products to market, the profits are kept entirely by the corporations or shared with the agencies or groups of government scientists. On the other hand, the public, who funded the research, receives no financial return. This amounts to a systemic betrayal of the public trust on a scale of hundreds of billions of dollars annually. Another significant contributor to rising healthcare costs is the widespread practice of defensive medicine that is driven by the constant threat of litigation. Over the past 40 years, defensive medicine has become a cottage industry. Physicians order excessive diagnostic tests and unnecessary treatments simply to protect themselves from lawsuits. Study after study has shown that these over-performed procedures not only inflate costs but lead to iatrogenesis or medical injury and death caused by the medical  system and practices itself. The solution is simple: adopting no-fault healthcare coverage for everyone where patients receive care without needing to sue and thereby freeing doctors from the burden of excessive malpractice insurance. A single-payer universal healthcare system could fundamentally transform the entire industry by capping profits at every level — from drug manufacturers to hospitals to medical equipment suppliers. The Department of Health and Human Services would have the authority to set profit margins for medical procedures. This would ensure that healthcare is determined by outcomes, not profits. Additionally, the growing influence of private equity firms and vulture capitalists buying up hospitals and medical clinics across America must be reined in. These equity firms prioritize profit extraction over improving the quality of care. They often slash staff, raise prices, and dictate medical procedures based on what will yield the highest returns. Another vital reform would be to provide free medical education for doctors and nurses in exchange for five years of service under the universal system. Medical professionals would earn a realistic salary cap to prevent them from being lured into equity partnerships or charging exorbitant rates. The biggest single expense in the current system, however, is the private health insurance industry, which consumes 33 percent of the $5 trillion healthcare budget. Health insurance CEOs consistently rank among the highest-paid executives in the country. Their companies, who are nothing more than bean counters, decide what procedures and drugs will be covered, partially covered, or denied altogether. This entire industry is designed to place profits above patients' lives. If the US dismantled its existing insurance-based system and replaced it with a fully reformed national healthcare model, the country could save $2.7 trillion annually while simultaneously improving health outcomes. Over the course of 10 years, those savings would amount to $27 trillion. This could wipe out nearly the entire national debt in a short time. This solution has been available for decades but has been systematically blocked by corporate lobbying and bipartisan corruption in Washington. The path forward is clear but only if American citizens demand a system where healthcare is valued as a public service and not a commodity. The national healthcare crisis is not just a fiscal issue. It is a crucial moral failure of the highest order. With the right reforms, the nation could simultaneously restore its financial health and deliver the kind of healthcare system its citizens have long deserved. American Healthcare: Corrupt, Broken and Lethal Richard Gale and Gary Null Progressive Radio Network, March 3, 2025 For a nation that prides itself on being the world's wealthiest, most innovative and technologically advanced, the US' healthcare system is nothing less than a disaster and disgrace. Not only are Americans the least healthy among the most developed nations, but the US' health system ranks dead last among high-income countries. Despite rising costs and our unshakeable faith in American medical exceptionalism, average life expectancy in the US has remained lower than other OECD nations for many years and continues to decline. The United Nations recognizes healthcare as a human right. In 2018, former UN Secretary General Ban Ki-moon denounced the American healthcare system as "politically and morally wrong." During the pandemic it is estimated that two to three years was lost on average life expectancy. On the other hand, before the Covid-19 pandemic, countries with universal healthcare coverage found their average life expectancy stable or slowly increasing. The fundamental problem in the U.S. is that politics have been far too beholden to the pharmaceutical, HMO and private insurance industries. Neither party has made any concerted effort to reign in the corruption of corporate campaign funding and do what is sensible, financially feasible and morally correct to improve Americans' quality of health and well-being.   The fact that our healthcare system is horribly broken is proof that moneyed interests have become so powerful to keep single-payer debate out of the media spotlight and censored. Poll after poll shows that the American public favors the expansion of public health coverage. Other incremental proposals, including Medicare and Medicaid buy-in plans, are also widely preferred to the Affordable Care Act or Obamacare mess we are currently stuck with.   It is not difficult to understand how the dismal state of American medicine is the result of a system that has been sold out to the free-market and the bottom line interests of drug makers and an inflated private insurance industry. How advanced and ethically sound can a healthcare system be if tens of millions of people have no access to medical care because it is financially out of their reach?  The figures speak for themselves. The U.S. is burdened with a $41 trillion Medicare liability. The number of uninsured has declined during the past several years but still lingers around 25 million. An additional 30-35 million are underinsured. There are currently 65 million Medicare enrollees and 89 million Medicaid recipients. This is an extremely unhealthy snapshot of the country's ability to provide affordable healthcare and it is certainly unsustainable. The system is a public economic failure, benefiting no one except the large and increasingly consolidated insurance and pharmaceutical firms at the top that supervise the racket.   Our political parties have wrestled with single-payer or universal healthcare for decades. Obama ran his first 2008 presidential campaign on a single-payer platform. Since 1985, his campaign health adviser, the late Dr. Quentin Young from the University of Illinois Medical School, was one of the nation's leading voices calling for universal health coverage.  During a private conversation with Dr. Young shortly before his passing in 2016, he conveyed his sense of betrayal at the hands of the Obama administration. Dr. Young was in his 80s when he joined the Obama campaign team to help lead the young Senator to victory on a promise that America would finally catch up with other nations. The doctor sounded defeated. He shared how he was manipulated, and that Obama held no sincere intention to make universal healthcare a part of his administration's agenda. During the closed-door negotiations, which spawned the weak and compromised Affordable Care Act, Dr. Young was neither consulted nor invited to participate. In fact, he told us that he never heard from Obama again after his White House victory.   Past efforts to even raise the issue have been viciously attacked. A huge army of private interests is determined to keep the public enslaved to private insurers and high medical costs. The failure of our healthcare is in no small measure due to it being a fully for-profit operation. Last year, private health insurance accounted for 65 percent of coverage. Consider that there are over 900 private insurance companies in the US. National Health Expenditures (NHE) grew to $4.5 trillion in 2022, which was 17.3 percent of GDP. Older corporate rank-and-file Democrats and Republicans argue that a single-payer or socialized medical program is unaffordable. However, not only is single-payer affordable, it will end bankruptcies due to unpayable medical debt. In addition, universal healthcare, structured on a preventative model, will reduce disease rates at the outset.    Corporate Democrats argue that Obama's Affordable Care Act (ACA) was a positive step inching the country towards complete public coverage. However, aside from providing coverage to the poorest of Americans, Obamacare turned into another financial anchor around the necks of millions more. According to the health policy research group KFF, the average annual health insurance premium for single coverage is $8,400 and almost $24,000 for a family. In addition, patient out-of-pocket costs continue to increase, a 6.6% increase to $471 billion in 2022. Rather than healthcare spending falling, it has exploded, and the Trump and Biden administrations made matters worse.    Clearly, a universal healthcare program will require flipping the script on the entire private insurance industry, which employed over half a million people last year.  Obviously, the most volatile debate concerning a national universal healthcare system concerns cost. Although there is already a socialized healthcare system in place -- every federal legislator, bureaucrat, government employee and veteran benefits from it -- fiscal Republican conservatives and groups such as the Koch Brothers network are single-mindedly dedicated to preventing the expansion of Medicare and Medicaid. A Koch-funded Mercatus analysis made the outrageous claim that a single-payer system would increase federal health spending by $32 trillion in ten years. However, analyses and reviews by the Congressional Budget Office in the early 1990s concluded that such a system would only increase spending at the start; enormous savings would quickly offset it as the years pass. In one analysis, "the savings in administrative costs [10 percent of health spending] would be more than enough to offset the expense of universal coverage."    Defenders of those advocating for funding a National Health Program argue this can primarily be accomplished by raising taxes to levels comparable to other developed nations. This was a platform Senator Bernie Sanders and some of the younger progressive Democrats in the House campaigned on. The strategy was to tax the highest multimillion-dollar earners 60-70 percent. Despite the outrage of its critics, including old rank-and-file multi-millionaire Democrats like Nancy Pelosi and Chuck Schumer, this is still far less than in the past. During the Korean War, the top tax rate was 91 percent; it declined to 70 percent in the late 1960s. Throughout most of the 1970s, those in the lowest income bracket were taxed at 14 percent. We are not advocating for this strategy because it ignores where the funding is going, and the corruption in the system that is contributing to exorbitant waste.    But Democratic supporters of the ACA who oppose a universal healthcare plan ignore the additional taxes Obama levied to pay for the program. These included surtaxes on investment income, Medicare taxes from those earning over $200,000, taxes on tanning services, an excise tax on medical equipment, and a 40 percent tax on health coverage for costs over the designated cap that applied to flexible savings and health savings accounts. The entire ACA was reckless, sloppy and unnecessarily complicated from the start.    The fact that Obamacare further strengthened the distinctions between two parallel systems -- federal and private -- with entirely different economic structures created a labyrinth of red tape, rules, and wasteful bureaucracy. Since the ACA went into effect, over 150 new boards, agencies and programs have had to be established to monitor its 2,700 pages of gibberish. A federal single-payer system would easily eliminate this bureaucracy and waste.    A medical New Deal to establish universal healthcare coverage is a decisive step in the correct direction. But we must look at the crisis holistically and in a systematic way. Simply shuffling private insurance into a federal Medicare-for-all or buy-in program, funded by taxing the wealthiest of citizens, would only temporarily reduce costs. It will neither curtail nor slash escalating disease rates e. Any effective healthcare reform must also tackle the underlying reasons for Americans' poor state of health. We cannot shy away from examining the social illnesses infecting our entire free-market capitalist culture and its addiction to deregulation. A viable healthcare model would have to structurally transform how the medical economy operates. Finally, a successful medical New Deal must honestly evaluate the best and most reliable scientific evidence in order to effectively redirect public health spending.    For example, Dr. Ezekiel Emanuel, a former Obama healthcare adviser, observed that AIDS-HIV measures consume the most public health spending, even though the disease "ranked 75th on the list of diseases by personal health expenditures." On the other hand, according to the American Medical Association, a large percentage of the nation's $3.4 trillion healthcare spending goes towards treating preventable diseases, notably diabetes, common forms of heart disease, and back and neck pain conditions. In 2016, these three conditions were the most costly and accounted for approximately $277 billion in spending. Last year, the CDC announced the autism rate is now 1 in 36 children compared to 1 in 44 two years ago. A retracted study by Mark Blaxill, an autism activist at the Holland Center and a friend of the authors, estimates that ASD costs will reach $589 billion annually by 2030. There are no signs that this alarming trend will reverse and decline; and yet, our entire federal health system has failed to conscientiously investigate the underlying causes of this epidemic. All explanations that might interfere with the pharmaceutical industry's unchecked growth, such as over-vaccination, are ignored and viciously discredited without any sound scientific evidence. Therefore, a proper medical New Deal will require a systemic overhaul and reform of our federal health agencies, especially the HHS, CDC and FDA. Only the Robert Kennedy Jr presidential campaign is even addressing the crisis and has an inexpensive and comprehensive plan to deal with it. For any medical revolution to succeed in advancing universal healthcare, the plan must prioritize spending in a manner that serves public health and not private interests. It will also require reshuffling private corporate interests and their lobbyists to the sidelines, away from any strategic planning, in order to break up the private interests' control over federal agencies and its revolving door policies. Aside from those who benefit from this medical corruption, the overwhelming majority of Americans would agree with this criticism. However, there is a complete lack of national trust that our legislators, including the so-called progressives, would be willing to undertake such actions.    In addition, America's healthcare system ignores the single most critical initiative to reduce costs - that is, preventative efforts and programs instead of deregulation and closing loopholes designed to protect the drug and insurance industries' bottom line. Prevention can begin with banning toxic chemicals that are proven health hazards associated with current disease epidemics, and it can begin by removing a 1,000-plus toxins already banned in Europe. This should be a no-brainer for any legislator who cares for public health. For example, Stacy Malkan, co-founder of the Campaign for Safe Cosmetics, notes that "the policy approach in the US and Europe is dramatically different" when it comes to chemical allowances in cosmetic products. Whereas the EU has banned 1,328 toxic substances from the cosmetic industry alone, the US has banned only 11. The US continues to allow carcinogenic formaldehyde, petroleum, forever chemicals, many parabens (an estrogen mimicker and endocrine hormone destroyer), the highly allergenic p-phenylenediamine or PBD, triclosan, which has been associated with the rise in antibiotic resistant bacteria, avobenzone, and many others to be used in cosmetics, sunscreens, shampoo and hair dyes.   Next, the food Americans consume can be reevaluated for its health benefits. There should be no hesitation to tax the unhealthiest foods, such as commercial junk food, sodas and candy relying on high fructose corn syrup, products that contain ingredients proven to be toxic, and meat products laden with dangerous chemicals including growth hormones and antibiotics. The scientific evidence that the average American diet is contributing to rising disease trends is indisputable. We could also implement additional taxes on the public advertising of these demonstrably unhealthy products. All such tax revenue would accrue to a national universal health program to offset medical expenditures associated with the very illnesses linked to these products. Although such tax measures would help pay for a new medical New Deal, it may be combined with programs to educate the public about healthy nutrition if it is to produce a reduction in the most common preventable diseases. In fact, comprehensive nutrition courses in medical schools should be mandatory because the average physician receives no education in this crucial subject.  In addition, preventative health education should be mandatory throughout public school systems.   Private insurers force hospitals, clinics and private physicians into financial corners, and this is contributing to prodigious waste in money and resources. Annually, healthcare spending towards medical liability insurance costs tens of billions of dollars. In particular, this economic burden has taxed small clinics and physicians. It is well past the time that physician liability insurance is replaced with no-fault options. Today's doctors are spending an inordinate amount of money to protect themselves. Legions of liability and trial lawyers seek big paydays for themselves stemming from physician error. This has created a culture of fear among doctors and hospitals, resulting in the overly cautious practice of defensive medicine, driving up costs and insurance premiums just to avoid lawsuits. Doctors are forced to order unnecessary tests and prescribe more medications and medical procedures just to cover their backsides. No-fault insurance is a common-sense plan that enables physicians to pursue their profession in a manner that will reduce iatrogenic injuries and costs. Individual cases requiring additional medical intervention and loss of income would still be compensated. This would generate huge savings.    No other nation suffers from the scourge of excessive drug price gouging like the US. After many years of haggling to lower prices and increase access to generic drugs, only a minute amount of progress has been made in recent years. A 60 Minutes feature about the Affordable Care Act reported an "orgy of lobbying and backroom deals in which just about everyone with a stake in the $3-trillion-a-year health industry came out ahead—except the taxpayers.” For example, Life Extension magazine reported that an antiviral cream (acyclovir), which had lost its patent protection, "was being sold to pharmacies for 7,500% over the active ingredient cost. The active ingredient (acyclovir) costs only 8 pennies, yet pharmacies are paying a generic maker $600 for this drug and selling it to consumers for around $700." Other examples include the antibiotic Doxycycline. The price per pill averages 7 cents to $3.36 but has a 5,300 percent markup when it reaches the consumer. The antidepressant Clomipramine is marked up 3,780 percent, and the anti-hypertensive drug Captopril's mark-up is 2,850 percent. And these are generic drugs!    Medication costs need to be dramatically cut to allow drug manufacturers a reasonable but not obscene profit margin. By capping profits approximately 100 percent above all costs, we would save our system hundreds of billions of dollars. Such a measure would also extirpate the growing corporate misdemeanors of pricing fraud, which forces patients to pay out-of-pocket in order to make up for the costs insurers are unwilling to pay.    Finally, we can acknowledge that our healthcare is fundamentally a despotic rationing system based upon high insurance costs vis-a-vis a toss of the dice to determine where a person sits on the economic ladder. For the past three decades it has contributed to inequality. The present insurance-based economic metrics cast millions of Americans out of coverage because private insurance costs are beyond their means. Uwe Reinhardt, a Princeton University political economist, has called our system "brutal" because it "rations [people] out of the system." He defined rationing as "withholding something from someone that is beneficial." Discriminatory healthcare rationing now affects upwards to 60 million people who have been either priced out of the system or under insured. They make too much to qualify for Medicare under Obamacare, yet earn far too little to afford private insurance costs and premiums. In the final analysis, the entire system is discriminatory and predatory.    However, we must be realistic. Almost every member of Congress has benefited from Big Pharma and private insurance lobbyists. The only way to begin to bring our healthcare program up to the level of a truly developed nation is to remove the drug industry's rampant and unnecessary profiteering from the equation.     How did Fauci memory-hole a cure for AIDS and get away with it?   By Helen Buyniski   Over 700,000 Americans have died of AIDS since 1981, with the disease claiming some 42.3 million victims worldwide. While an HIV diagnosis is no longer considered a certain death sentence, the disease looms large in the public imagination and in public health funding, with contemporary treatments running into thousands of dollars per patient annually.   But was there a cure for AIDS all this time - an affordable and safe treatment that was ruthlessly suppressed and attacked by the US public health bureaucracy and its agents? Could this have saved millions of lives and billions of dollars spent on AZT, ddI and failed HIV vaccine trials? What could possibly justify the decision to disappear a safe and effective approach down the memory hole?   The inventor of the cure, Gary Null, already had several decades of experience creating healing protocols for physicians to help patients not responding well to conventional treatments by the time AIDS was officially defined in 1981. Null, a registered dietitian and board-certified nutritionist with a PhD in human nutrition and public health science, was a senior research fellow and Director of Anti-Aging Medicine at the Institute of Applied Biology for 36 years and has published over 950 papers, conducting groundbreaking experiments in reversing biological aging as confirmed with DNA methylation testing. Additionally, Null is a multi-award-winning documentary filmmaker, bestselling author, and investigative journalist whose work exposing crimes against humanity over the last 50 years has highlighted abuses by Big Pharma, the military-industrial complex, the financial industry, and the permanent government stay-behind networks that have come to be known as the Deep State.   Null was contacted in 1974 by Dr. Stephen Caiazza, a physician working with a subculture of gay men in New York living the so-called “fast track” lifestyle, an extreme manifestation of the gay liberation movement that began with the Stonewall riots. Defined by rampant sexual promiscuity and copious use of illegal and prescription drugs, including heavy antibiotic use for a cornucopia of sexually-transmitted diseases, the fast-track never included more than about two percent of gay men, though these dominated many of the bathhouses and clubs that defined gay nightlife in the era. These patients had become seriously ill as a result of their indulgence, generally arriving at the clinic with multiple STDs including cytomegalovirus and several types of herpes and hepatitis, along with candida overgrowth, nutritional deficiencies, gut issues, and recurring pneumonia. Every week for the next 10 years, Null would counsel two or three of these men - a total of 800 patients - on how to detoxify their bodies and de-stress their lives, tracking their progress with Caiazza and the other providers at weekly feedback meetings that he credits with allowing the team to quickly evaluate which treatments were most effective. He observed that it only took about two years on the “fast track” for a healthy young person to begin seeing muscle loss and the recurrent, lingering opportunistic infections that would later come to be associated with AIDS - while those willing to commit to a healthier lifestyle could regain their health in about a year.    It was with this background that Null established the Tri-State Healing Center in Manhattan in 1980, staffing the facility with what would eventually run to 22 certified health professionals to offer safe, natural, and effective low- and no-cost treatments to thousands of patients with HIV and AIDS-defining conditions. Null and his staff used variations of the protocols he had perfected with Caiazza's patients, a multifactorial patient-tailored approach that included high-dose vitamin C drips, intravenous ozone therapy, juicing and nutritional improvements and supplementation, aspects of homeopathy and naturopathy with some Traditional Chinese Medicine and Ayurvedic practices. Additional services offered on-site included acupuncture and holistic dentistry, while peer support groups were also held at the facility so that patients could find community and a positive environment, healing their minds and spirits while they healed their bodies.   “Instead of trying to kill the virus with antiretroviral pharmaceuticals designed to stop viral replication before it kills patients, we focused on what benefits could be gained by building up the patients' natural immunity and restoring biochemical integrity so the body could fight for itself,” Null wrote in a 2014 article describing the philosophy behind the Center's approach, which was wholly at odds with the pharmaceutical model.1   Patients were comprehensively tested every week, with any “recovery” defined solely by the labs, which documented AIDS patient after patient - 1,200 of them - returning to good health and reversing their debilitating conditions. Null claims to have never lost an AIDS patient in the Center's care, even as the death toll for the disease - and its pharmaceutical standard of care AZT - reached an all-time high in the early 1990s. Eight patients who had opted for a more intensive course of treatment - visiting the Center six days a week rather than one - actually sero-deconverted, with repeated subsequent testing showing no trace of HIV in their bodies.   As an experienced clinical researcher himself, Null recognized that any claims made by the Center would be massively scrutinized, challenging as they did the prevailing scientific consensus that AIDS was an incurable, terminal illness. He freely gave his protocols to any medical practitioner who asked, understanding that his own work could be considered scientifically valid only if others could replicate it under the same conditions. After weeks of daily observational visits to the Center, Dr. Robert Cathcart took the protocols back to San Francisco, where he excitedly reported that patients were no longer dying in his care.    Null's own colleague at the Institute of Applied Biology, senior research fellow Elana Avram, set up IV drip rooms at the Institute and used his intensive protocols to sero-deconvert 10 patients over a two-year period. While the experiment had been conducted in secret, as the Institute had been funded by Big Pharma since its inception half a century earlier, Avram had hoped she would be able to publish a journal article to further publicize Null's protocols and potentially help AIDS patients, who were still dying at incredibly high rates thanks to Burroughs Wellcome's noxious but profitable AZT. But as she would later explain in a 2019 letter to Null, their groundbreaking research never made it into print - despite meticulous documentation of their successes - because the Institute's director and board feared their pharmaceutical benefactors would withdraw the funding on which they depended, given that Null's protocols did not involve any patentable or otherwise profitable drugs. When Avram approached them about publication, the board vetoed the idea, arguing that it would “draw negative attention because [the work] was contrary to standard drug treatments.” With no real point in continuing experiments along those lines without institutional support and no hope of obtaining funding from elsewhere, the department she had created specifically for these experiments shut down after a two-year followup with her test subjects - all of whom remained alive and healthy - was completed.2   While the Center was receiving regular visits by this time from medical professionals and, increasingly, black celebrities like Stokely Carmichael and Isaac Hayes, who would occasionally perform for the patients, the news was spreading by word of mouth alone - not a single media outlet had dared to document the clinic that was curing AIDS patients for free. Instead, they gave airtime to Anthony Fauci, director of the National Institute of Allergies and Infectious Diseases, who had for years been spreading baseless, hysteria-fueling claims about HIV and AIDS to any news outlet that would put him on. His claim that children could contract the virus from “ordinary household conduct” with an infected relative proved so outrageous he had to walk it back,3 and he never really stopped insisting the deadly plague associated with gays and drug users was about to explode like a nuclear bomb among the law-abiding heterosexual population. Fauci by this time controlled all government science funding through NIAID, and his zero-tolerance approach to dissent on the HIV/AIDS front had already seen prominent scientists like virologist Peter Duesberg stripped of the resources they needed for their work because they had dared to question his commandment: There is no cause of AIDS but HIV, and AZT is its treatment. Even the AIDS activist groups, which by then had been coopted by Big Pharma and essentially reduced to astroturfing for the toxic failed chemotherapy drug AZT backed by the institutional might of Fauci's NIAID,4 didn't seem to want to hear that there was a cure. Unconcerned with the irrationality of denouncing the man touting his free AIDS cure as an  “AIDS denier,” they warned journalists that platforming Null or anyone else rejecting the mainstream medical line would be met with organized demands for their firing.    Determined to breach the institutional iron curtain and get his message to the masses, Null and his team staged a press conference in New York, inviting scientists and doctors from around the world to share their research on alternative approaches to HIV and AIDS in 1993. To emphasize the sound scientific basis of the Center's protocols and encourage guests to adopt them into their own practices, Null printed out thousands of abstracts in support of each nutrient and treatment being used. However, despite over 7,000 invitations sent three times to major media, government figures, scientists, and activists, almost none of the intended audience members showed up. Over 100 AIDS patients and their doctors, whose charts exhaustively documented their improvements using natural and nontoxic modalities over the preceding 12 months, gave filmed testimonials, declaring that the feared disease was no longer a death sentence, but the conference had effectively been silenced. Bill Tatum, publisher of the Amsterdam News, suggested Null and his patients would find a more welcoming audience in his home neighborhood of Harlem - specifically, its iconic Apollo Theatre. For three nights, the theater was packed to capacity. Hit especially hard by the epidemic and distrustful of a medical system that had only recently stopped being openly racist (the Tuskegee syphilis experiment only ended in 1972), black Americans, at least, did not seem to care what Anthony Fauci would do if he found out they were investigating alternatives to AZT and death.    PBS journalist Tony Brown, having obtained a copy of the video of patient testimonials from the failed press conference, was among a handful of black journalists who began visiting the Center to investigate the legitimacy of Null's claims. Satisfied they had something significant to offer his audience, Brown invited eight patients - along with Null himself - onto his program over the course of several episodes to discuss the work. It was the first time these protocols had received any attention in the media, despite Null having released nearly two dozen articles and multiple documentaries on the subject by that time. A typical patient on one program, Al, a recovered IV drug user who was diagnosed with AIDS at age 32, described how he “panicked,” saw a doctor and started taking AZT despite his misgivings - only to be forced to discontinue the drug after just a few weeks due to his condition deteriorating rapidly. Researching alternatives brought him to Null, and after six months of “detoxing [his] lifestyle,” he observed his initial symptoms - swollen lymph nodes and weight loss - begin to reverse, culminating with sero-deconversion. On Bill McCreary's Channel 5 program, a married couple diagnosed with HIV described how they watched their T-cell counts increase as they cut out sugar, caffeine, smoking, and drinking and began eating a healthy diet. They also saw the virus leave their bodies.   For HIV-positive viewers surrounded by fear and negativity, watching healthy-looking, cheerful “AIDS patients” detail their recovery while Null backed up their claims with charts must have been balm for the soul. But the TV programs were also a form of outreach to the medical community, with patients' charts always on hand to convince skeptics the cure was scientifically valid. Null brought patients' charts to every program, urging them to keep an open mind: “Other physicians and public health officials should know that there's good science in the alternative perspective. It may not be a therapy that they're familiar with, because they're just not trained in it, but if the results are positive, and you can document them…” He challenged doubters to send in charts from their own sero-deconverted patients on AZT, and volunteered to debate proponents of the orthodox treatment paradigm - though the NIH and WHO both refused to participate in such a debate on Tony Brown's Journal, following Fauci's directive prohibiting engagement with forbidden ideas.    Aside from those few TV programs and Null's own films, suppression of Null's AIDS cure beyond word of mouth was total. The 2021 documentary The Cost of Denial, produced by the Society for Independent Journalists, tells the story of the Tri-State Healing Center and the medical paradigm that sought to destroy it, lamenting the loss of the lives that might have been saved in a more enlightened society. Nurse practitioner Luanne Pennesi, who treated many of the AIDS patients at the Center, speculated in the film that the refusal by the scientific establishment and AIDS activists to accept their successes was financially motivated. “It was as if they didn't want this information to get out. Understand that our healthcare system as we know it is a corporation, it's a corporate model, and it's about generating revenue. My concern was that maybe they couldn't generate enough revenue from these natural approaches.”5   Funding was certainly the main disciplinary tool Fauci's NIAID used to keep the scientific community in line. Despite the massive community interest in the work being done at the Center, no foundation or institution would defy Fauci and risk getting itself blacklisted, leaving Null to continue funding the operation out of his pocket with the profits from book sales. After 15 years, he left the Center in 1995, convinced the mainstream model had so thoroughly been institutionalized that there was no chance of overthrowing it. He has continued to counsel patients and advocate for a reappraisal of the HIV=AIDS hypothesis and its pharmaceutical treatments, highlighting the deeply flawed science underpinning the model of the disease espoused by the scientific establishment in 39 articles, six documentaries and a 700-page textbook on AIDS, but the Center's achievements have been effectively memory-holed by Fauci's multi-billion-dollar propaganda apparatus.     FRUIT OF THE POISONOUS TREE   To understand just how much of a threat Null's work was to the HIV/AIDS establishment, it is instructive to revisit the 1984 paper, published by Dr. Robert Gallo of the National Cancer Institute, that established HIV as the sole cause of AIDS. The CDC's official recognition of AIDS in 1981 had done little to quell the mounting public panic over the mysterious illness afflicting gay men in the US, as the agency had effectively admitted it had no idea what was causing them to sicken and die. As years passed with no progress determining the causative agent of the plague, activist groups like Gay Men's Health Crisis disrupted public events and threatened further mass civil disobedience as they excoriated the NIH for its sluggish allocation of government science funding to uncovering the cause of the “gay cancer.”6 When Gallo published his paper declaring that the retrovirus we now know as HIV was the sole “probable” cause of AIDS, its simple, single-factor hypothesis was the answer to the scientific establishment's prayers. This was particularly true for Fauci, as the NIAID chief was able to claim the hot new disease as his agency's own domain in what has been described as a “dramatic confrontation” with his rival Sam Broder at the National Cancer Institute. After all, Fauci pointed out, Gallo's findings - presented by Health and Human Services Secretary Margaret Heckler as if they were gospel truth before any other scientists had had a chance to inspect them, never mind conduct a full peer review - clearly classified AIDS as an infectious disease, and not a cancer like the Kaposi's sarcoma which was at the time its most visible manifestation. Money and media attention began pouring in, even as funding for the investigation of other potential causes of AIDS dried up. Having already patented a diagnostic test for “his” retrovirus before introducing it to the world, Gallo was poised for a financial windfall, while Fauci was busily leveraging the discovery into full bureaucratic empire of the US scientific apparatus.   While it would serve as the sole basis for all US government-backed AIDS research to follow - quickly turning Gallo into the most-cited scientist in the world during the 1980s,7 Gallo's “discovery” of HIV was deeply problematic. The sample that yielded the momentous discovery actually belonged to Prof. Luc Montagnier of the French Institut Pasteur, a fact Gallo finally admitted in 1991, four years after a lawsuit from the French government challenged his patent on the HIV antibody test, forcing the US government to negotiate a hasty profit-sharing agreement between Gallo's and Montagnier's labs. That lawsuit triggered a cascade of official investigations into scientific misconduct by Gallo, and evidence submitted during one of these probes, unearthed in 2008 by journalist Janine Roberts, revealed a much deeper problem with the seminal “discovery.” While Gallo's co-author, Mikulas Popovic, had concluded after numerous experiments with the French samples that the virus they contained was not the cause of AIDS, Gallo had drastically altered the paper's conclusion, scribbling his notes in the margins, and submitted it for publication to the journal Science without informing his co-author.   After Roberts shared her discovery with contacts in the scientific community, 37 scientific experts wrote to the journal demanding that Gallo's career-defining HIV paper be retracted from Science for lacking scientific integrity.8 Their call, backed by an endorsement from the 2,600-member scientific organization Rethinking AIDS, was ignored by the publication and by the rest of mainstream science despite - or perhaps because of - its profound implications.   That 2008 letter, addressed to Science editor-in-chief Bruce Alberts and copied to American Association for the Advancement of Science CEO Alan Leshner, is worth reproducing here in its entirety, as it utterly dismantles Gallo's hypothesis - and with them the entire HIV is the sole cause of AIDS dogma upon which the contemporary medical model of the disease rests:   On May 4, 1984 your journal published four papers by a group led by Dr. Robert Gallo. We are writing to express our serious concerns with regard to the integrity and veracity of the lead paper among these four of which Dr. Mikulas Popovic is the lead author.[1] The other three are also of concern because they rely upon the conclusions of the lead paper .[2][3][4]  In the early 1990s, several highly critical reports on the research underlying these papers were produced as a result of governmental inquiries working under the supervision of scientists nominated by the National Academy of Sciences and the Institute of Medicine. The Office of Research Integrity of the US Department of Health and Human Services concluded that the lead paper was “fraught with false and erroneous statements,” and that the “ORI believes that the careless and unacceptable keeping of research records...reflects irresponsible laboratory management that has permanently impaired the ability to retrace the important steps taken.”[5] Further, a Congressional Subcommittee on Oversight and Investigations led by US Representative John D. Dingell of Michigan produced a staff report on the papers which contains scathing criticisms of their integrity.[6]  Despite the publically available record of challenges to their veracity, these papers have remained uncorrected and continue to be part of the scientific record.  What prompts our communication today is the recent revelation of an astonishing number of previously unreported deletions and unjustified alterations made by Gallo to the lead paper. There are several documents originating from Gallo's laboratory that, while available for some time, have only recently been fully analyzed. These include a draft of the lead paper typewritten by Popovic which contains handwritten changes made to it by Gallo.[7] This draft was the key evidence used in the above described inquiries to establish that Gallo had concealed his laboratory's use of a cell culture sample (known as LAV) which it received from the Institut Pasteur.  These earlier inquiries verified that the typed manuscript draft was produced by Popovic who had carried out the recorded experiment while his laboratory chief, Gallo, was in Europe and that, upon his return, Gallo changed the document by hand a few days before it was submitted to Science on March 30, 1984. According to the ORI investigation, “Dr. Gallo systematically rewrote the manuscript for what would become a renowned LTCB [Gallo's laboratory at the National Cancer Institute] paper.”[5]  This document provided the important evidence that established the basis for awarding Dr. Luc Montagnier and Dr. Francoise Barré-Sinoussi the 2008 Nobel Prize in Medicine for the discovery of the AIDS virus by proving it was their samples of LAV that Popovic used in his key experiment. The draft reveals that Popovic had forthrightly admitted using the French samples of LAV renamed as Gallo's virus, HTLV-III, and that Gallo had deleted this admission, concealing their use of LAV.  However, it has not been previously reported that on page three of this same document Gallo had also deleted Popovic's unambiguous statement that, "Despite intensive research efforts, the causative agent of AIDS has not yet been identified,” replacing it in the published paper with a statement that said practically the opposite, namely, “That a retrovirus of the HTLV family might be an etiologic agent of AIDS was suggested by the findings.”  It is clear that the rest of Popovic's typed paper is entirely consistent with his statement that the cause of AIDS had not been found, despite his use of the French LAV. Popovic's final conclusion was that the culture he produced “provides the possibility” for detailed studies. He claimed to have achieved nothing more. At no point in his paper did Popovic attempt to prove that any virus caused AIDS, and it is evident that Gallo concealed these key elements in Popovic's experimental findings.  It is astonishing now to discover these unreported changes to such a seminal document. We can only assume that Gallo's alterations of Popovic's conclusions were not highlighted by earlier inquiries because the focus at the time was on establishing that the sample used by Gallo's lab came from Montagnier and was not independently collected by Gallo. In fact, the only attention paid to the deletions made by Gallo pertains to his effort to hide the identity of the sample. The questions of whether Gallo and Popovic's research proved that LAV or any other virus was the cause of AIDS were clearly not considered.  Related to these questions are other long overlooked documents that merit your attention. One of these is a letter from Dr. Matthew A. Gonda, then Head of the Electron Microscopy Laboratory at the National Cancer Institute, which is addressed to Popovic, copied to Gallo and dated just four days prior to Gallo's submission to Science.[8] In this letter, Gonda remarks on samples he had been sent for imaging because “Dr Gallo wanted these micrographs for publication because they contain HTLV.” He states, “I do not believe any of the particles photographed are of HTLV-I, II or III.” According to Gonda, one sample contained cellular debris, while another had no particles near the size of a retrovirus. Despite Gonda's clearly worded statement, Science published on May 4, 1984 papers attributed to Gallo et al with micrographs attributed to Gonda and described unequivocally as HTLV-III.  In another letter by Gallo, dated one day before he submitted his papers to Science, Gallo states, “It's extremely rare to find fresh cells [from AIDS patients] expressing the virus... cell culture seems to be necessary to induce virus,” a statement which raises the possibility he was working with a laboratory artifact. [9]  Included here are copies of these documents and links to the same. The very serious flaws they reveal in the preparation of the lead paper published in your journal in 1984 prompts our request that this paper be withdrawn. It appears that key experimental findings have been concealed. We further request that the three associated papers published on the same date also be withdrawn as they depend on the accuracy of this paper.  For the scientific record to be reliable, it is vital that papers shown to be flawed, or falsified be retracted. Because a very public record now exists showing that the Gallo papers drew unjustified conclusions, their withdrawal from Science is all the more important to maintain integrity. Future researchers must also understand they cannot rely on the 1984 Gallo papers for statements about HIV and AIDS, and all authors of papers that previously relied on this set of four papers should have the opportunity to consider whether their own conclusions are weakened by these revelations.      Gallo's handwritten revision, submitted without his colleague's knowledge despite multiple experiments that failed to support the new conclusion, was the sole foundation for the HIV=AIDS hypothesis. Had Science published the manuscript the way Popovic had typed it, there would be no AIDS “pandemic” - merely small clusters of people with AIDS. Without a viral hypothesis backing the development of expensive and deadly pharmaceuticals, would Fauci have allowed these patients to learn about the cure that existed all along?   Faced with a potential rebellion, Fauci marshaled the full resources under his control to squelch the publication of the investigations into Gallo and restrict any discussion of competing hypotheses in the scientific and mainstream press, which had been running virus-scare stories full-time since 1984. The effect was total, according to biochemist Dr. Kary Mullis, inventor of the polymerase chain reaction (PCR) procedure. In a 2009 interview, Mullis recalled his own shock when he attempted to unearth the experimental basis for the HIV=AIDS hypothesis. Despite his extensive inquiry into the literature, “there wasn't a scientific reference…[that] said ‘here's how come we know that HIV is the probable cause of AIDS.' There was nothing out there like that.”9 This yawning void at the core of HIV/AIDS “science" turned him into a strident critic of AIDS dogma - and those views made him persona non grata where the scientific press was concerned, suddenly unable to publish a single paper despite having won the Nobel Prize for his invention of the PCR test just weeks before.  10   DISSENT BECOMES “DENIAL”   While many of those who dissent from the orthodox HIV=AIDS view believe HIV plays a role in the development of AIDS, they point to lifestyle and other co-factors as being equally if not more important. Individuals who test positive for HIV can live for decades in perfect health - so long as they don't take AZT or the other toxic antivirals fast-tracked by Fauci's NIAID - but those who developed full-blown AIDS generally engaged in highly risky behaviors like extreme promiscuity and prodigious drug abuse, contracting STDs they took large quantities of antibiotics to treat, further running down their immune systems. While AIDS was largely portrayed as a “gay disease,” it was only the “fast track” gays, hooking up with dozens of partners nightly in sex marathons fueled by “poppers” (nitrate inhalants notorious for their own devastating effects on the immune system), who became sick. Kaposi's sarcoma, one of the original AIDS-defining conditions, was widespread among poppers-using gay men, but never appeared among IV drug users or hemophiliacs, the other two main risk groups during the early years of the epidemic. Even Robert Gallo himself, at a 1994 conference on poppers held by the National Institute on Drug Abuse, would admit that the previously-rare form of skin cancer surging among gay men was not primarily caused by HIV - and that it was immune stimulation, rather than suppression, that was likely responsible.11 Similarly, IV drug users are often riddled with opportunistic infections as their habit depresses the immune system and their focus on maintaining their addiction means that healthier habits - like good nutrition and even basic hygiene - fall by the wayside.    Supporting the call for revising the HIV=AIDS hypothesis to include co-factors is the fact that the mass heterosexual outbreaks long predicted by Fauci and his ilk in seemingly every country on Earth have failed to materialize, except - supposedly - in Africa, where the diagnostic standard for AIDS differs dramatically from those of the West. Given the prohibitively high cost of HIV testing for poor African nations, the WHO in 1985 crafted a diagnostic loophole that became known as the “Bangui definition,” allowing medical professionals to diagnose AIDS in the absence of a test using just clinical symptoms: high fever, persistent cough, at least 30 days of diarrhea, and the loss of 10% of one's body weight within two months. Often suffering from malnutrition and without access to clean drinking water, many of the inhabitants of sub-Saharan Africa fit the bill, especially when the WHO added tuberculosis to the list of AIDS-defining illnesses in 1993 - a move which may be responsible for as many as one half of African “AIDS” cases, according to journalist Christine Johnson. The WHO's former Chief of Global HIV Surveillance, James Chin, acknowledged their manipulation of statistics, but stressed that it was the entire AIDS industry - not just his organization - perpetrating the fraud. “There's the saying that, if you knew what sausages are made of, most people would hesitate to sort of eat them, because they wouldn't like what's in it. And if you knew how HIV/AIDS numbers are cooked, or made up, you would use them with extreme caution,” Chin told an interviewer in 2009.12   With infected numbers stubbornly remaining constant in the US despite Fauci's fearmongering projections of the looming heterosexually-transmitted plague, the CDC in 1993 broadened its definition of AIDS to include asymptomatic (that is, healthy) HIV-positive people with low T-cell counts - an absurd criteria given that an individual's T-cell count can fluctuate by hundreds within a single day. As a result, the number of “AIDS cases” in the US immediately doubled. Supervised by Fauci, the NIAID had been quietly piling on diseases into the “AIDS-related” category for years, bloating the list from just two conditions - pneumocystis carinii pneumonia and Kaposi's sarcoma - to 30 so fast it raised eyebrows among some of science's leading lights. Deeming the entire process “bizarre” and unprecedented, Kary Mullis wondered aloud why no one had called the AIDS establishment out: “There's something wrong here. And it's got to be financial.”13   Indeed, an early CDC public relations campaign was exposed by the Wall Street Journal in 1987 as having deliberately mischaracterized AIDS as a threat to the entire population so as to garner increased public and private funding for what was very much a niche issue, with the risk to average heterosexuals from a single act of sex “smaller than the risk of ever getting hit by lightning.” Ironically, the ads, which sought to humanize AIDS patients in an era when few Americans knew anyone with the disease and more than half the adult population thought infected people should be forced to carry cards warning of their status, could be seen as a reaction to the fear tactics deployed by Fauci early on.14   It's hard to tell where fraud ends and incompetence begins with Gallo's HIV antibody test. Much like Covid-19 would become a “pandemic of testing,” with murder victims and motorcycle crashes lumped into “Covid deaths” thanks to over-sensitized PCR tests that yielded as many as 90% false positives,15 HIV testing is fraught with false positives - and unlike with Covid-19, most people who hear they are HIV-positive still believe they are receiving a death sentence. Due to the difficulty of isolating HIV itself from human samples, the most common diagnostic tests, ELISA and the Western Blot, are designed to detect not the virus but antibodies to it, upending the traditional medical understanding that the presence of antibodies indicates only exposure - and often that the body has actually vanquished the pathogen. Patients are known to test positive for HIV antibodies in the absence of the virus due to at least 70 other conditions, including hepatitis, lupus, rheumatoid arthritis, syphilis, recent vaccination or even pregnancy. (https://www.chcfl.org/diseases-that-can-cause-a-false-positive-hiv-test/) Positive results are often followed up with a PCR “viral load” test, even though the inventor of the PCR technique Kary Mullis famously condemned its misuse as a tool for diagnosing infection. Packaging inserts for all three tests warn the user that they cannot be reliably used to diagnose HIV.16 The ELISA HIV antibody test explicitly states: “At present there is no recognized standard for establishing the presence and absence of HIV antibody in human blood.”17   That the public remains largely unaware of these and other massive holes in the supposedly airtight HIV=AIDS=DEATH paradigm is a testament to Fauci's multi-layered control of the press. Like the writers of the Great Barrington Declaration and other Covid-19 dissidents, scientists who question HIV/AIDS dogma have been brutally punished for their heresy, no matter how prestigious their prior standing in the field and no matter how much evidence they have for their own claims. In 1987, the year the FDA's approval of AZT made AIDS the most profitable epidemic yet (a dubious designation Covid-19 has since surpassed), Fauci made it clearer than ever that scientific inquiry and debate - the basis of the scientific method - would no longer be welcome in the American public health sector, eliminating retrovirologist Peter Duesberg, then one of the most prominent opponents of the HIV=AIDS hypothesis, from the scientific conversation with a professional disemboweling that would make a cartel hitman blush. Duesberg had just eviscerated Gallo's 1984 HIV paper with an article of his own in the journal Cancer Research, pointing out that retroviruses had never before been found to cause a single disease in humans - let alone 30 AIDS-defining diseases. Rather than allow Gallo or any of the other scientists in his camp to respond to the challenge, Fauci waged a scorched-earth campaign against Duesberg, who had until then been one of the most highly regarded researchers in his field. Every research grant he requested was denied; every media appearance was canceled or preempted. The University of California at Berkeley, unable to fully fire him due to tenure, took away his lab, his graduate students, and the rest of his funding. The few colleagues who dared speak up for him in public were also attacked, while enemies and opportunists were encouraged to slander Duesberg at the conferences he was barred from attending and in the journals that would no longer publish his replies. When Duesberg was summoned to the White House later that year by then-President Ronald Reagan to debate Fauci on the origins of AIDS, Fauci convinced the president to cancel, allegedly pulling rank on the Commander-in-Chief with an accusation that the “White House was interfering in scientific matters that belonged to the NIH and the Office of Science and Technology Assessment.” After seven years of this treatment, Duesberg was contacted by NIH official Stephen O'Brien and offered an escape from professional purgatory. He could have “everything back,” he was told, and shown a manuscript of a scientific paper - apparently commissioned by the editor of the journal Nature - “HIV Causes AIDS: Koch's Postulates Fulfilled” with his own name listed alongside O'Brien's as an author.18 His refusal to take the bribe effectively guaranteed the epithet “AIDS denier” will appear on his tombstone. The character assassination of Duesberg became a template that would be deployed to great effectiveness wherever Fauci encountered dissent - never debate, only demonize, deplatform and destroy.    Even Luc Montagnier, the real discoverer of HIV, soon found himself on the wrong side of the Fauci machine. With his 1990 declaration that “the HIV virus [by itself] is harmless and passive, a benign virus,” Montagnier began distancing himself from Gallo's fraud, effectively placing a target on his own back. In a 1995 interview, he elaborated: “four factors that have come together to account for the sudden epidemic [of AIDS]: HIV presence, immune hyper-activation, increased sexually transmitted disease incidence, sexual behavior changes and other behavioral changes” such as drug use, poor nutrition and stress - all of which he said had to occur “essentially simultaneously” for HIV to be transmitted, creating the modern epidemic. Like the professionals at the Tri-State Healing Center, Montagnier advocated for the use of antioxidants like vitamin C and N-acetyl cysteine, naming oxidative stress as a critical factor in the progression from HIV to AIDS.19 When Montagnier died in 2022, Fauci's media mouthpieces sneered that the scientist (who was awarded the Nobel Prize in 2008 for his discovery of HIV, despite his flagging faith in that discovery's significance) “started espousing views devoid of a scientific basis” in the late 2000s, leading him to be “shunned by the scientific community.”20 In a particularly egregious jab, the Washington Post's obit sings the praises of Robert Gallo, implying it was the American scientist who really should have won the Nobel for HIV, while dismissing as “

MILANO (ITALPRESS) - Nel corso di "SkinLongevity", magazine televisivo dell'agenzia Italpress, Antonino Di Pietro, direttore dell'Istituto Dermoclinico Vita Cutis, intervista Lucia Brambilla, dermatologa e responsabile dell'ambulatorio Sarcoma di Kaposi - U.O. Dermatologia Ospedale Policlinico di Milano. Tra i temi del colloquio, il sarcoma di Kaposi.sat/gsl

MILANO (ITALPRESS) - Tutto per una lunga vita della pelle, sana, giovane e bella. Nella settima puntata di Skinlongevity Magazine, nuovo format Tv dell'agenzia di stampa Italpress, Antonino Di Pietro, direttore dell'Istituto Dermoclinico Vita Cutis di Milano del Gruppo San Donato, intervista Angelo Valerio Marzano, dermatologo e direttore della struttura complessa Dermatologia, Ospedale Policlinico - Università degli Studi di Milano, e Lucia Brambilla, dermatologa e responsabile dell'ambulatorio Sarcoma di Kaposi - unità operativa Dermatologia Ospedale Policlinico di Milano. Al centro della puntata l'osservatorio del Policlinico di Milano su epidermolisi bollosa e sarcoma di Kaposi.sat/gsl

Dr. Patrick Danaher, Infectious Diseases Clinician at the USF Morsani College of Medicine, discusses the various dermatologic manifestations of HIV in this recorded session. Among the topics discussed includes genital herpes disease, Zoster, Mpox infections, MRSA skin lesions, and Kaposi sarcoma. The lecture is presented in a case-based format.

Dr Edson José Boccardo Médico Infectologista Hospital Emílio Ribas A história do HIV iniciou-se em 1978 com alguns casos no Haiti e na África. O vírus foi isolado em 1983 por um cientista francês. Porém, o primeiro relato surgiu com um caso de pneumonia diferente, pneumocistose em 1990. Outos casos de doenças atípicas surgiram como sarcoma de Kaposi. Estudando estes casos demonstraram que a imunidade desses pacientes era muito baixa. Percebeu-se que a população com este vírus era predominante entre homossexuais, pessoas que recebiam transfusão de sangue e usuários de drogas. Pessoas com AIDS (doença associada ao HIV) era fatal em praticamente todos os casos, pois as células do corpo para combate à infecção eram todas atingidas deixando o corpo suscetível a infecções raras que eram fatais para os pacientes. O principal mecanismo de transmissão é a relação sexual, ainda transfusão de sangue apesar de mais raros, e compartilhamento de seringas no uso de drogas injetáveis. Importante ressaltar que atualmente a relação heterossexual é a predominante na transmissão do HIV. Infelizmente a maioria da população jovem não utiliza mais o preservativo para ter relações e a incidência não só da AIDS, como sifilis, hepatites, entre outras infeções, aumentou muito. As novas medicações são muito eficientes e com menos numero de compridos e algumas medicações são injetáveis e podem tomar a medicação uma vez ao mês. A chance de desenvolvimento da doença com essas medicações é muito baixa. O tratamento pós exposição é para pacientes que se descuidaram durante a relação, sem preservativo, com pessoas desconhecidas, etc. Primeiro faz-se o teste rápido em até 72 horas, se for negativo, faz-se a medicação (o coquetel) por 28 dias para impedir a entrada do vírus na célula. Esse tratamento reduz a chance de infecção em mais de 90%. O prep é mais recente, utilizado na pessoa que tem comportamento de risco ou o parceiro: essa pessoa toma medicação para evitar contrair a doença, porém o tratamento é mais longo. Importante ressaltar que esses tratamentos não previnem as outras infecções sexualmente transmissíveis. Alguns pacientes são chamados de “controlador de elite” que é positivo, porém com carga viral baixa ou praticamente zero e não desenvolve a doença. Esses pacientes, que são raros, não necessitam de tratamento. O rastreio das infecções sexualmente transmissíveis deve fazer parte do check up inclusive para HIV pelo menos uma vez ao ano. As técnicas de rastreio para HIV estão muito refinadas e são capazes de detectar baixas quantidades de vírus. As hepatites B e C também são doenças sexualmente transmissíveis. A hepatite B foi primeira hepatite identificada e pode ser transmitida pelas relações sexuais, transfusão e compartilhamento de seringas. Além disso, a hepatite B pode ser transmitida em acidentes com agulhas, uso de alicates, tatuagens, barbeadores, etc.. em 20%, pois o vírus vive muito tempo em superfícies (20% de chance de transmissão). 90% de quem contrai desenvolve anticorpos e eliminam o vírus. Os outros 10 % podem ter cronificação da doença e desenvolver câncer de fígado ou cirrose: as hepatites são as principais causas de cirrose no Brasil. O paciente pode ficar assintomático até 6 meses e o paciente não sabe, podendo transmitir a doença. Após 20 anos pode apresentar alterações hepáticas. Atualmente as novas medicações tem menos efeitos colaterais com maior poder de cura; um comprimido por dia por 12 semanas com redução significativa da carga viral em 98% dos casos. A hepatite B pode ser previnida com vacina. O mecanismo de contágio de hepatite C é a mesmo da B. A chance de cronificação dessa doença é de 70% e também pode causar cirrose e câncer de fígado. Essa doença não tem vacina, porém o tratamento eficaz reduz a carga viral em 2 meses. #aids #hepatite

Alors qu'Haïti est toujours en proie aux violences des gangs et fait face à une grave crise humanitaire, nous évoquons la situation sanitaire de ce pays qui compte, selon l'ONU, près de 600 000 déplacés pour 11,5 millions d'habitants. Le 26 août 2024, la Mission multinationale d'appui à la sécurité (MMAS) affirmait avoir « enregistré des progrès significatifs », permettant de reprendre aux gangs « le contrôle d'infrastructures essentielles, comme l'aéroport ». Ces progrès se ressentent-ils sur le plan de la santé ? Comment assurer une continuité des soins dans ce contexte ? Quel impact sur la santé mentale des Haïtiens ? Benoît Vasseur, chef de mission Médecins Sans Frontières en Haïti Dr Marie-Marcelle Deschamps, directrice adjointe de l'Institution des centres Gheskio (Groupe d'étude haïtien sur le sarcome de Kaposi et les infections opportunistes) Ronald Jean-Jacques, psychologue et professeur à l'Université d'État d'Haïti, co-auteur de Haïti, recréer la vie, des traumatismes aux processus résilients créateurs, paru dans la Revue haïtienne de santé mentale qu'il co-dirige.Programmation musicale :►Tropicana – Ayiti Bel► Abou Tall – Bats-toi.

Alors qu'Haïti est toujours en proie aux violences des gangs et fait face à une grave crise humanitaire, nous évoquons la situation sanitaire de ce pays qui compte, selon l'ONU, près de 600 000 déplacés pour 11,5 millions d'habitants. Le 26 août 2024, la Mission multinationale d'appui à la sécurité (MMAS) affirmait avoir « enregistré des progrès significatifs », permettant de reprendre aux gangs « le contrôle d'infrastructures essentielles, comme l'aéroport ». Ces progrès se ressentent-ils sur le plan de la santé ? Comment assurer une continuité des soins dans ce contexte ? Quel impact sur la santé mentale des Haïtiens ? Benoît Vasseur, chef de mission Médecins Sans Frontières en Haïti Dr Marie-Marcelle Deschamps, directrice adjointe de l'Institution des centres Gheskio (Groupe d'étude haïtien sur le sarcome de Kaposi et les infections opportunistes) Ronald Jean-Jacques, psychologue et professeur à l'Université d'État d'Haïti, co-auteur de Haïti, recréer la vie, des traumatismes aux processus résilients créateurs, paru dans la Revue haïtienne de santé mentale qu'il co-dirige.Programmation musicale :►Tropicana – Ayiti Bel► Abou Tall – Bats-toi.

Alors qu'Haïti est toujours en proie aux violences des gangs et fait face à une grave crise humanitaire, nous évoquons la situation sanitaire de ce pays qui compte, selon l'ONU, près de 600 000 déplacés pour 11,5 millions d'habitants.  Avec :  Dr Marie-Marcelle Deschamps, Directrice adjointe de l'institution des centres Gheskio (Groupe d'étude haïtien sur le sarcome de Kaposi et les infections opportunistes)

The most enthralling conversation I've ever had with anyone on cancer. It's with Charlie Swanton who is a senior group leader at the Francis Crick Institute, the Royal Society Napier Professor in Cancer and medical oncologist at University College London, co-director of Cancer Research UK.Video snippet from our conversation. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with audio links and many external linksEric Topol (00:07):Well, hello, this is Eric Topol with Ground Truths, and I am really fortunate today to connect us with Charlie Swanton, who is if not the most prolific researcher in the space of oncology and medicine, and he's right up there. Charlie is a physician scientist who is an oncologist at Francis Crick and he heads up the lung cancer area there. So Charlie, welcome.Charles Swanton (00:40):Thank you, Eric. Nice to meet you.Learning from a FailureEric Topol (00:43):Well, it really is a treat because I've been reading your papers and they're diverse. They're not just on cancer. Could be connecting things like air pollution, it could be Covid, it could be AI, all sorts of things. And it's really quite extraordinary. So I thought I'd start out with a really interesting short paper you wrote towards the end of last year to give a sense about you. It was called Turning a failing PhD around. And that's good because it's kind of historical anchoring. Before we get into some of your latest contributions, maybe can you tell us about that story about what you went through with your PhD?Charles Swanton (01:26):Yeah, well thank you, Eric. I got into research quite early. I did what you in the US would call the MD PhD program. So in my twenties I started a PhD in a molecular biology lab at what was then called the Imperial Cancer Research Fund, which was the sort of the mecca for DNA tumor viruses, if you like. It was really the place to go if you wanted to study how DNA tumor viruses worked, and many of the components of the cell cycle were discovered there in the 80s and 90s. Of course, Paul Nurse was the director of the institute at the time who discovered cdc2, the archetypal regulator of the cell cycle that led to his Nobel Prize. So it was a very exciting place to work, but my PhD wasn't going terribly well. And sort of 18, 19 months into my PhD, I was summoned for my midterm reports and it was not materializing rapidly enough.(02:25):And I sat down with my graduate student supervisors who were very kind, very generous, but basically said, Charlie, this isn't going well, is it? You've got two choices. You can either go back to medical school or change PhD projects. What do you want to do? And I said, well, I can't go back to medical school because I'm now two years behind. So instead I think what I'll do is I'll change PhD projects. And they asked me what I'd like to do. And back then we didn't know how p21, the CDK inhibitor bound to cyclin D, and I said, that's what I want to understand how these proteins interact biochemically. And they said, how are you going to do that? And I said, I'm not too sure, but maybe we'll try yeast two-hybrid screen and a mutagenesis screen. And that didn't work either. And in the end, something remarkable happened.(03:14):My PhD boss, Nic Jones, who's a great guy, still is, retired though now, but a phenomenal scientist. He put me in touch with a colleague who actually works next door to me now at the Francis Crick Institute called Neil McDonald, a structural biologist. And they had just solved, well, the community had just solved the structure. Pavletich just solved the structure of cyclin A CDK2. And so, Neil could show me this beautiful image of the crystal structure in 3D of cyclin A, and we could mirror cyclin D onto it and find the surface residue. So I spent the whole of my summer holiday mutating every surface exposed acid on cyclin D to an alanine until I found one that failed to interact with p21, but could still bind the CDK. And that little breakthrough, very little breakthrough led to this discovery that I had where the viral cyclins encoded by Kaposi sarcoma herpes virus, very similar to cyclin D, except in this one region that I had found interactive with a CDK inhibitor protein p21.(04:17):And so, I asked my boss, what do you think about the possibility this cyclin could have evolved from cyclin D but now mutated its surface residues in a specific area so that it can't be inhibited by any of the control proteins in the mammalian cell cycle? He said, it's a great idea, Charlie, give it a shot. And it worked. And then six months later, we got a Nature paper. And that for me was like, I cannot tell you how exciting, not the Nature paper so much as the discovery that you were the first person in the world to ever see this beautiful aspect of evolutionary biology at play and how this cyclin had adapted to just drive the cell cycle without being inhibited. For me, just, I mean, it was like a dream come true, and I never experienced anything like it before, and I guess it's sizes the equivalent to me of a class A drug. You get such a buzz out of it and over the years you sort of long for that to happen again. And occasionally it does, and it's just a wonderful profession.Eric Topol (05:20):Well, I thought that it was such a great story because here you were about to fail. I mean literally fail, and you really were able to turn it around and it should give hope to everybody working in science out there that they could just be right around the corner from a significant discovery.Charles Swanton (05:36):I think what doesn't break you makes you stronger. You just got to plow on if you love it enough, you'll find a way forward eventually, I hope.Tracing the Evolution of Cancer (TRACERx)Eric Topol (05:44):Yeah, no question about that. Now, some of your recent contributions, I mean, it's just amazing to me. I just try to keep up with the literature just keeping up with you.Charles Swanton (05:58):Eric, it's sweet of you. The first thing to say is it's not just me. This is a big community of lung cancer researchers we have thanks to Cancer Research UK funded around TRACERx and the lung cancer center. Every one of my papers has three corresponding authors, multiple co-first authors that all contribute in this multidisciplinary team to the sort of series of small incremental discoveries. And it's absolutely not just me. I've got an amazing team of scientists who I work with and learn from, so it's sweet to give me the credit.Eric Topol (06:30):I think what you're saying is really important. It is a team, but I think what I see through it all is that you're an inspiration to the team. You pull people together from all over the world on these projects and it's pretty extraordinary, so that's what I would say.Charles Swanton (06:49):The lung community, Eric, the lung cancer community is just unbelievably conducive to collaboration and advancing understanding of the disease together. It's just such a privilege to be working in this field. I know that sounds terribly corny, but it is true. I don't think I recall a single email to anybody where I've asked if we can collaborate where they've said, no, everybody wants to help. Everybody wants to work together on this challenge. It's just such an amazing field to be working in.Eric Topol (07:19):Yeah. Well I was going to ask you about that. And of course you could have restricted your efforts or focused on different cancers. What made you land in lung cancer? Not that that's only part of what you're working on, but that being the main thing, what drew you to that area?Charles Swanton (07:39):So I think the answer to your question is back in 2008 when I was looking for a niche, back then it was lung cancer was just on the brink of becoming an exciting place to work, but back then nobody wanted to work in that field. So there was a chair position in thoracic oncology and precision medicine open at University College London Hospital that had been open, as I understand it for two years. And I don't think anybody had applied. So I applied and because I was the only one, I got it and the rest is history.(08:16):And of course that was right at the time when the IPASS draft from Tony Mok was published and was just a bit after when the poster child of EGFR TKIs and EGFR mutant lung cancer had finally proven that if you segregate that population of patients with EGFR activating mutation, they do incredibly well on an EGFR inhibitor. And that was sort of the solid tumor poster child along with Herceptin of precision medicine, I think. And you saw the data at ASCO this week of Lorlatinib in re-arranged lung cancer. Patients are living way beyond five years now, and people are actually talking about this disease being more like CML. I mean, it's extraordinary the progress that's been made in the last two decades in my short career.Eric Topol (09:02):Actually, I do want to have you put that in perspective because it's really important what you just mentioned. I was going to ask you about this ASCO study with the AKT subgroup. So the cancer landscape of the lung has changed so much from what used to be a disease of cigarette smoking to now one of, I guess adenocarcinoma, non-small cell carcinoma, not related to cigarettes. We're going to talk about air pollution in a minute. This group that had, as you say, 60 month, five year plus survival versus what the standard therapy was a year plus is so extraordinary. But is that just a small subgroup within small cell lung cancer?Charles Swanton (09:48):Yes, it is, unfortunately. It's just a small subgroup. In our practice, probably less than 1% of all presentations often in never smokers, often in female, never smokers. So it is still in the UK at least a minority subset of adenocarcinomas, but it's still, as you rightly say, a minority of patients that we can make a big difference to with a drug that's pretty well tolerated, crosses the blood-brain barrier and prevents central nervous system relapse and progression. It really is an extraordinary breakthrough, I think. But that said, we're also seeing advances in smoking associated lung cancer with a high mutational burden with checkpoint inhibitor therapy, particularly in the neoadjuvant setting now prior to surgery. That's really, really impressive indeed. And adjuvant checkpoint inhibitor therapies as well as in the metastatic setting are absolutely improving survival times and outcomes now in a way that we couldn't have dreamt of 15 years ago. We've got much more than just platinum-based chemo is basically the bottom line now.Revving Up ImmunotherapyEric Topol (10:56):Right, right. Well that actually gets a natural question about immunotherapy also is one of the moving parts actually just amazing to me how that's really, it's almost like we're just scratching the surface of immunotherapy now with checkpoint inhibitors because the more we get the immune system revved up, the more we're seeing results, whether it's with vaccines or CAR-T, I mean it seems like we're just at the early stages of getting the immune system where it needs to be to tackle the cancer. What's your thought about that?Charles Swanton (11:32):I think you're absolutely right. We are, we're at the beginning of a very long journey thanks to Jim Allison and Honjo. We've got CTLA4 and PD-1/PDL-1 axis to target that's made a dramatic difference across multiple solid tumor types including melanoma and lung cancer. But undoubtedly, there are other targets we've seen LAG-3 and melanoma and then we're seeing new ways, as you rightly put it to mobilize the immune system to target cancers. And that can be done through vaccine based approaches where you stimulate the immune system against the patient's specific mutations in their cancer or adoptive T-cell therapies where you take the T-cells out of the tumor, you prime them against the mutations found in the tumor, you expand them and then give them back to the patient. And colleagues in the US, Steve Rosenberg and John Haanen in the Netherlands have done a remarkable job there in the context of melanoma, we're not a million miles away from European approvals and academic initiated manufacturing of T-cells for patients in national health systems like in the Netherlands.(12:50):John Haanen's work is remarkable in that regard. And then there are really spectacular ways of altering T-cells to be able to either migrate to the tumor or to target specific tumor antigens. You mentioned CAR-T cell therapies in the context of acute leukemia, really extraordinary developments there. And myeloma and diffuse large B-cell lymphoma as well as even in solid tumors are showing efficacy. And I really am very excited about the future of what we call biological therapies, be it vaccines, an antibody drug conjugates and T-cell therapies. I think cancer is a constantly adapting evolutionary force to be reckoned with what better system to combat it than our evolving immune system. It strikes me as being a future solution to many of these refractory cancers we still find difficult to treat.Eric Topol (13:48):Yeah, your point is an interesting parallel how the SARS-CoV-2 virus is constantly mutating and becoming more evasive as is the tumor in a person and the fact that we can try to amp up the immune system with these various means that you just were reviewing. You mentioned the other category that's very hot right now, which is the antibody drug conjugates. Could you explain a bit about how they work and why you think this is an important part of the future for cancer?Antibody-Drug ConjugatesCharles Swanton (14:26):That's a great question. So one of the challenges with chemotherapy, as you know, is the normal tissue toxicity. So for instance, neutropenia, hair loss, bowel dysfunction, diarrhea, epithelial damage, essentially as you know, cytotoxics affect rapidly dividing tissues, so bone marrow, epithelial tissues. And because until relatively recently we had no way of targeting chemotherapy patients experienced side effects associated with them. So over the last decade or so, pioneers in this field have brought together this idea of biological therapies linked with chemotherapy through a biological linker. And so one poster chart of that would be the drug T-DXd, which is essentially Herceptin linked to a chemotherapy drug. And this is just the most extraordinary drug that obviously binds the HER2 receptor, but brings the chemotherapy and proximity of the tumor. The idea being the more drug you can get into the tumor and the less you're releasing into normal tissue, the more on tumor cytotoxicity you'll have and the less off tumor on target normal tissue side effects you'll have. And to a large extent, that's being shown to be the case. That doesn't mean they're completely toxicity free, they're not. And one of the side effects associated with these drugs is pneumonitis.(16:03):But that said, the efficacy is simply extraordinary. And for example, we're having to rewrite the rule books if you like, I think. I mean I'm not a breast cancer physician, I used to be a long time ago, but back in the past in the early 2000s, there was HER2 positive breast cancer and that's it. Now they're talking about HER2 low, HER2 ultra-low, all of which seem to in their own way be sensitive to T-DXd, albeit to a lower extent than HER2 positive disease. But the point is that there doesn't seem to be HER2 completely zero tumor group in breast cancer. And even the HER2-0 seem to benefit from T-DXd to an extent. And the question is why? And I think what people are thinking now is it's a combination of very low cell service expression of HER2 that's undetectable by conventional methods like immunohistochemistry, but also something exquisitely specific about the way in which HER2 is mobilized on the membrane and taken back into the cell. That seems to be specific to the breast cancer cell but not normal tissue. So in other words, the antibody drug conjugate binds the tumor cell, it's thought the whole receptor's internalized into the endosome, and that's where the toxicity then happens. And it's something to do with the endosomal trafficking with the low level expression and internalization of the receptor. That may well be the reason why these HER2 low tumors are so sensitive to this beautiful technology.Eric Topol (17:38):Now I mean it is an amazing technology in all these years where we just were basically indiscriminately trying to kill cells and hoping that the cancer would succumb. And now you're finding whether you want to call it a carry or vector or Trojan horse, whatever you want to call it, but do you see that analogy of the HER2 receptor that's going to be seen across the board in other cancers?Charles Swanton (18:02):That's the big question, Eric. I think, and have we just lucked out with T-DXd, will we find other T-DXd like ADCs targeting other proteins? I mean there are a lot of ADCs being developed against a lot of different cell surface proteins, and I think the jury's still out. I'm confident we will, but we have to bear in mind that biology is a fickle friend and there may be something here related to the internalization of the receptor in breast cancer that makes this disease so exquisitely sensitive. So I think we just don't know yet. I'm reasonably confident that we will find other targets that are as profoundly sensitive as HER2 positive breast cancer, but time will tell.Cancer, A Systemic DiseaseEric Topol (18:49):Right. Now along these lines, well the recent paper that you had in Cell, called embracing cancer complexity, which we've talking about a bit, in fact it's kind of those two words go together awfully well, but hallmarks of systemic disease, this was a masterful review, as you say with the team that you led. But can you tell us about what's your main perspective about this systemic disease? I mean obviously there's been the cancer is like cardiovascular and cancers like this or that, but here you really brought it together with systemic illness. What can you say about that?Charles Swanton (19:42):Well, thanks for the question first of all, Eric. So a lot of this comes from some of my medical experience of treating cancer and thinking to myself over the years, molecular biology has had a major footprint on advances in treating the disease undoubtedly. But there are still aspects of medicine where molecular biology has had very little impact, and often that is in areas of suffering in patients with advanced disease and cancer related to things like cancer cachexia, thrombophilia. What is the reason why patients die blood clots? What is the reason patients die of cancer at all? Even a simple question like that, we don't always know the answer to, on death certificates, we write metastatic disease as a cause of cancer death, but we have patients who die with often limited disease burden and no obvious proximal cause of death sometimes. And that's very perplexing, and we need to understand that process better.(20:41):And we need to understand aspects like cancer pain, for example, circadian rhythms affect biological sensitivity of cancer cells to drugs and what have you. Thinking about cancer rather than just sort of a single group of chaotically proliferating cells to a vision of cancer interacting both locally within a microenvironment but more distantly across organs and how organs communicate with the cancer through neuronal networks, for example, I think is going to be the next big challenge by setting the field over the next decade or two. And I think then thinking about more broadly what I mean by embracing complexity, I think some of that relates to the limitations of the model systems we use, trying to understand inter-organ crosstalk, some of the things you cover in your beautiful Twitter reviews. (←Ground Truths link) I remember recently you highlighted four publications that looked at central nervous system, immune cell crosstalk or central nervous system microbiome crosstalk. It's this sort of long range interaction between organs, between the central nervous system and the immune system and the cancer that I'm hugely interested in because I really think there are vital clues there that will unlock new targets that will enable us to control cancers more effectively if we just understood these complex networks better and had more sophisticated animal model systems to be able to interpret these interactions.Eric Topol (22:11):No, it's so important what you're bringing out, the mysteries that still we have to deal with cancer, why patients have all these issues or dying without really knowing what's happened no less, as you say, these new connects that are being discovered at a remarkable pace, as you mentioned, that ground truths. And also, for example, when I spoke with Michelle Monje, she's amazing on the cancer, where hijacking the brain cells and just pretty extraordinary things. Now that gets me to another line of work of yours. I mean there are many, but the issue of evolution of the tumor, and if you could put that in context, a hot area that's helping us elucidate these mechanisms is known as spatial omics or spatial biology. This whole idea of being able to get the spatial temporal progression through single cell sequencing and single cell nuclei, all the single cell omics. So if you could kind of take us through what have we learned with this technique and spatial omics that now has changed or illuminated our understanding of how cancer evolves?Charles Swanton (23:37):Yeah, great question. Well, I mean I think it helps us sort of rewind a bit and think about evolution in general. Genetic selection brought about by diverse environments and environmental pressures that force evolution, genetic evolution, and speciation down certain evolutionary roots. And I think one can think about cancers in a similar way. They start from a single cell and we can trace the evolutionary paths of cancers by single cell analysis as well as bulk sequencing of spatially separated tumor regions to be able to reconstruct their subclones. And that's taught us to some extent, what are the early events in tumor evolution? What are the biological mechanisms driving branched evolution? How does genome instability begin in tumors? And we found through TRACERx work, whole genome doubling is a major route through to driving chromosome instability along with mutagenic enzymes like APOBEC that drive both mutations and chromosomal instability.(24:44):And then that leads to a sort of adaptive radiation in a sense, not dissimilar to I guess the Cambrian explosion of evolutionary opportunity upon which natural selection can act. And that's when you start to see the hallmarks of immune evasion like loss of HLA, the immune recognition molecules that bind the neoantigens or even loss of the neoantigens altogether or mutation of beta 2 microglobulin that allow the tumor cells to now evolve below the radar, so to speak. But you allude to the sort of spatial technologies that allow us to start to interpret the microenvironments as well. And that then tells us what the evolutionary pressures are upon the tumor. And we're learning from those spatial technologies that these environments are incredibly diverse, actually interestingly seem to be converging on one important aspect I'd like to talk to you a little bit more about, which is the myeloid axis, which is these neutrophils, macrophages, et cetera, that seem to be associated with poor outcome and that will perhaps talk about pollution in a minute.(25:51):But I think they're creating a sort of chronic inflammatory response that allows these early nascent tumor cells to start to initiate into frankly tumor invasive cells and start to grow. And so, what we're seeing from these spatial technologies in lung cancer is that T-cells, predatory T-cells, force tumors to lose their HLA molecules and what have you to evade the immune system. But for reasons we don't understand, high neutrophil infiltration seems to be associated with poor outcome, poor metastasis free survival. And actually, those same neutrophils we've recently found actually even tracked to the metastasis sites of metastasis. So it's almost like this sort of symbiosis between the myeloid cells and the tumor cells in their biology and growth and progression of the tumor cells.Eric Topol (26:46):Yeah, I mean this white cell story, this seems to be getting legs and is relatively new, was this cracked because of the ability to do this type of work to in the past everything was, oh, it's cancer's heterogeneous and now we're getting pinpoint definition of what's going on.Charles Swanton (27:04):I think it's certainly contributed, but it's like everything in science, Eric, when you look back, there's evidence in the literature for pretty much everything we've ever discovered. You just need to put the pieces together. And I mean one example would be the neutrophil lymphocyte ratio in the blood as a hallmark of outcome in cancers and to checkpoint inhibitor blockade, maybe this begins to explain it, high neutrophils, immune suppressive environment, high neutrophils, high macrophages, high immune suppression, less benefit from checkpoint inhibitor therapy, whereas you want lymphocyte. So I think there are biomedical medical insights that help inform the biology we do in the lab that have been known for decades or more. And certainly the myeloid M2 axis in macrophages and what have you was known about way before these spatial technologies really came to fruition, I think.The Impact of Air PollutionEric Topol (28:01):Yeah. Well you touched on this about air pollution and that's another dimension of the work that you and your team have done. As you well know, there was a recent global burden of disease paper in the Lancet, which has now said that air pollution with particulate matter 2.5 less is the leading cause of the burden of disease in the world now.Charles Swanton (28:32):What did you think of that, Eric?Eric Topol (28:34):I mean, I was blown away. Totally blown away. And this is an era you've really worked on. So can you put it in perspective?Charles Swanton (28:42):Yeah. So we got into this because patients of mine, and many of my colleagues would ask the same question, I've never smoked doctor, I'm healthy. I'm in my mid 50s though they're often female and I've got lung cancer. Why is that doctor? I've had a good diet, I exercise, et cetera. And we didn't really have a very good answer for that, and I don't want to pretend for a minute we solved the whole problem. I think hopefully we've contributed to a little bit of understanding of why this may happen. But that aside, we knew that there were risk factors associated with lung cancer that included air pollution, radon exposure, of course, germline genetics, we mustn't forget very important germline variation. And I think there is evidence that all of them are associated with lung cancer risk in different ways. But we wanted to look at air pollution, particularly because there was an awful lot of evidence, several meta-analysis of over half a million individuals showing very convincingly with highly significant results that increasing PM 2.5 micron particulate levels were associated with increased risk of lung cancer.(29:59):To put that into perspective, where you are on the west coast of the US, it's relatively unpolluted. You would be talking about maybe five micrograms per meter cubed of PM2.5 in a place like San Diego or Western California, assuming there aren't any forest fires of course. And we estimate that that would translate to about, we think it's about one extra case of never smoking lung cancer per hundred thousand of the population per year per one microgram per meter cube rise in the pollution levels. So if you go to Beijing for example, on a bad day, the air pollution levels could be upwards of a hundred micrograms per meter cubed because there are so many coal fired power stations in China partly. And there I think the risk is considerably higher. And that's certainly what we've seen in the meta-analyses in our limited and relatively crude epidemiological analyses to be the case.(30:59):So I think the association was pretty certain, we were very confident from people's prior publications  this was important. But of course, association is not causation. So we took a number of animal models and showed that you could promote lung cancer formation in four different oncogene driven lung cancer models. And then the question is how, does air pollution stimulate mutations, which is what I initially thought it would do or something else. It turns out we don't see a significant increase in exogenous like C to A carcinogenic mutations. So that made us put our thinking caps on. And I said to you earlier, often all these discoveries have been made before. Well, Berenblum in 1947, first postulated that actually tumors are initiated through a two-step process, which we now know involves a sort of pre initiated cell with a mutation in that in itself is not sufficient to cause cancer.(31:58):But on top of that you need an inflammatory stimulus. So the question was then, well, okay, is inflammation working here? And we found that there was an interleukin-1 beta axis. And what happens is that the macrophages come into the lung on pollution exposure, engulf phagocytose the air pollutants, and we think what's happening is the air pollutants are puncturing membranes in the lung. That's what we think is happening. And interleukin-1 beta preformed IL-1 beta is being released into the extracellular matrix and then stimulating pre-initiated cells stem cells like the AT2 cells with an activating EGFR mutation to form a tumor. But the EGFR mutation alone is not sufficient to form tumors. It's only when you have the interleukin-1 beta and the activated mutation that a tumor can start.(32:49):And we found that if we sequence normal lung tissue in a healthy adult 60-year-old adult, we will find about half of biopsies will have an activating KRAS mutation in normal tissue, and about 15% will have an activating mutation in EGFR in histologically normal tissue with nerve and of cancer. In fact, my friend and colleague who's a co-author on the paper, James DeGregori, who you should speak to in Colorado, fascinating evolutionary cancer biologists estimates that in a healthy 60-year-old, there are a hundred billion cells in your body that harbor an oncogenic mutation. So that tells you that at the cellular level, cancer is an incredibly rare event and almost never happens. I mean, our lifetime risk of cancer is perhaps one in two. You covered that beautiful pancreas paper recently where they estimated that there may be 80 to 100 KRAS mutations in a normal adult pancreas, and yet our lifetime risk of pancreas cancer is one in 70. So this tells you that oncogenic mutations are rarely sufficient to drive cancer, so something else must be happening. And in the context of air pollution associated lung cancer, we think that's inflammation driven by these white cells, these myeloid cells, the macrophages.Cancer BiomarkersEric Topol (34:06):No, it makes a lot of sense. And this, you mentioned the pancreas paper and also what's going in the lung, and it seems like we have this burden of all you need is a tipping point and air pollution seems to qualify, and you seem to be really in the process of icing the mechanism. And like I would've thought it was just mutagenic and it's not so simple, right? But that gets me to this is such an important aspect of cancer, the fact that we harbor these kind of preconditions. And would you think that cancer takes decades to actually manifest most cancers, or do we really have an opportunity here to be able to track whether it's through blood or other biomarkers? Another area you've worked on a lot whereby let's say you could define people at risk for polygenic risk scores or various cancers or genome sequencing for predisposition genes, whatever, and you could monitor in the future over the course of those high-risk people, whether they were starting to manifest microscopic malignancy. Do you have any thoughts about how long it takes for the average person to actually manifest a typical cancer?Charles Swanton (35:28):That's a cracking question, and the answer is we've got some clues in various cancers. Peter Campbell would be a good person to speak to. He estimates that some of the earliest steps in renal cancer can occur in adolescence. We've had patients who gave up smoking 30 or so years ago where we can still see the clonal smoking mutations in the trunk of the tumor's evolutionary tree. So the initial footprints of the cancer are made 30 years before the cancer presents. That driver mutation itself may also be a KRAS mutation in a smoking cigarette context, G12C mutation. And those mutations can precede the diagnosis of the disease by decades. So the earliest steps in cancer evolution can occur, we think can precede diagnoses by a long time. So to your point, your question which is, is there an opportunity to intervene? I'm hugely optimistic about this actually, this idea of molecular cancer prevention.An Anti-Inflammatory Drug Reduces Fatal Cancer and Lung Cancer(36:41):How can we use data coming out of various studies in the pancreas, mesothelioma, lung, et cetera to understand the inflammatory responses? I don't think we can do very much about the mutations. The mutations unfortunately are a natural consequence of aging. You and I just sitting here talking for an hour will have accumulated multiple mutations in our bodies over that period, I'm afraid and there's no escaping it. And right now there's not much we can do to eradicate those mutant clones. So if we take that as almost an intractable problem, measuring them is hard enough, eradicating them is even harder. And then we go back to Berenblum in 1947 who said, you need an inflammatory stimulus. Well, could we do something about the inflammation and dampen down the inflammation? And of course, this is why we got so excited about IL-1 beta because of the CANTOS trial, which you may remember in 2017 from Ridker and colleagues showed that anti IL-1 beta used as a mechanism of preventing cardiovascular events was associated with a really impressive dose dependent reduction in new lung cancer primaries.(37:49):Really a beautiful example of cancer prevention in action. And that data weren't just a coincidence. The FDA mandated Novartis to collect the solid tumor data and the P-values are 0.001. I mean it's very highly significant dose dependent reduction in lung cancer incidents associated with anti IL-1 beta. So I think that's really the first clue in my mind that something can be done about this problem. And actually they had five years of follow-up, Eric. So that's something about that intervening period where you can treat and then over time see a reduction in new lung cancers forming. So I definitely think there's a window of opportunity here.Eric Topol (38:31):Well, what you're bringing up is fascinating here because this trial, which was a cardiology trial to try to reduce heart attacks, finds a reduction in cancer, and it's been lost. It's been buried. I mean, no one's using this therapy to prevent cancer between ratcheting up the immune system or decreasing inflammation. We have opportunities that we're not even attempting. Are there any trials that are trying to do this sort of thing?Charles Swanton (39:02):So this is the fundamental problem. Nobody wants to invest in prevention because essentially you are dealing with well individuals. It's like the vaccine challenge all over again. And the problem is you never know who you are benefiting. There's no economic model for it. So pharma just won't touch prevention with a barge pole right now. And that's the problem. There's no economic model for it. And yet the community, all my academic colleagues are crying out saying, this has got to be possible. This has got to be possible. So CRUK are putting together a group of like-minded individuals to see if we can do something here and we're gradually making progress, but it is tough.Eric Topol (39:43):And it's interesting that you bring that up because for GRAIL, one of the multicenter cancer early detection companies, they raised billions of dollars. And in fact, their largest trial is ongoing in the UK, but they haven't really focused on high-risk people. They just took anybody over age 50 or that sort of thing. But that's the only foray to try to reboot how we or make an early microscopic diagnosis of cancer and track people differently. And there's an opportunity there. You've written quite a bit on you and colleagues of the blood markers being able to find a cancer where well before, in fact, I was going to ask you about that is, do you think there's people that are not just having all these mutations every minute, every hour, but that are starting to have the early seeds of cancer, but because their immune system then subsequently kicks in that they basically kind of quash it for that period of time?Charles Swanton (40:47):Yeah, I do think that, I mean, the very fact that we see these sort of footprints in the tumor genome of immune evasion tells you that the immune system's having a very profound predatory effect on evolving tumors. So I do think it's very likely that there are tumors occurring that are suppressed by the immune system. There is a clear signature, a signal of negative selection in tumors where clones have been purified during their evolution by the immune system. So I think there's pretty strong evidence for that now. Obviously, it's very difficult to prove something existed when it doesn't now exist, but there absolutely is evidence for that. I think it raises the interesting question of immune system recognizes mutations and our bodies are replete with mutations as we were just discussing. Why is it that we're not just a sort of epithelial lining of autoimmunity with T-cells and immune cells everywhere? And I think what the clever thing about the immune system is it's evolved to target antigens only when they get above a certain burden. Otherwise, I think our epithelial lining, our skin, our guts, all of our tissues will be just full of T-cells eating away our normal clones.(42:09):These have to get to a certain size for antigen to be presented at a certain level for the immune system to recognize it. And it's only then that you get the immune predation occurring.Forever Chemicals and Microplastics Eric Topol (42:20):Yeah, well, I mean this is opportunities galore here. I also wanted to extend the air pollution story a bit. Obviously, we talked about particulate matter and there's ozone and nitric NO2, and there's all sorts of other air pollutants, but then there's also in the air and water these forever chemicals PFAS for abbreviation, and they seem to be incriminated like air pollution. Can you comment about that?Charles Swanton (42:55):Well, I can comment only insofar as to say I'm worried about the situation. Indeed, I'm worried about microplastics actually, and you actually cover that story as well in the New England Journal, the association of microplastics with plaque rupture and atheroma. And indeed, just as in parenthesis, I wanted to just quickly say we currently think the same mechanisms that are driving lung cancer are probably responsible for atheroma and possibly even neurodegenerative disease. And essentially it all comes down to the macrophages and the microglia becoming clogged up with these pollutants or environmental particulars and releasing chronic inflammatory mediators that ultimately lead to disease. And IL-1 beta being one of those in atheroma and probably IL-6 and TNF in neurodegenerative disease and what have you. But I think this issue that you rightly bring up of what is in our environment and how does it cause pathology is really something that epidemiologists have spent a lot of time focusing on.(43:56):But actually in terms of trying to move from association to causation, we've been, I would argue a little bit slow biologically in trying to understand these issues. And I think that is a concern. I mean, to give you an example, Allan Balmain, who works at UCSF quite close to you, published a paper in 2020 showing that 17 out of 20 environmental carcinogens IARC carcinogens class one carcinogens cause tumors in rodent models without driving mutations. So if you take that to a logical conclusion, in my mind, what worries me is that many of the sort of carcinogen assays are based on driving mutagenesis genome instability. But if many carcinogen aren't driving DNA mutagenesis but are still driving cancer, how are they doing it? And do we actually have the right assays to interpret safety of new chemical matter that's being introduced into our environment, these long-lived particles that we're breathing in plastics, pollutants, you name it, until we have the right biological assays, deeming something to be safe I think is tricky.Eric Topol (45:11):Absolutely. And I share your concerns on the nanoplastic microplastic story, as you well know, not only have they been seen in arteries that are inflamed and in blood clots and in various tissues, have they been seen so far or even looked for within tumor tissue?Charles Swanton (45:33):Good question. I'm not sure they have. I need to check. What I can tell you is we've been doing some experiments in the lab with fluorescent microplastics, 2.5 micron microplastics given inhaled microplastics. We find them in every mouse organ a week after. And these pollutants even get through into the brain through the olfactory bulb we think.Charles Swanton (45:57):Permeate every tissue, Eric.Eric Topol (45:59):Yeah, no, this is scary because here we are, we have these potentially ingenious ways to prevent cancer in the future, but we're chasing our tails by not doing anything to deal with our environment.Charles Swanton (46:11):I think that's right. I totally agree. Yeah.Eric Topol (46:15):So I mean, I can talk to you for the rest of the day, but I do want to end up with a topic that we have mutual interest in, which is AI. And also along with that, when you mentioned about aging, I'd like to get your views on these two, how do you see AI fitting into the future of cancer? And then the more general topic is, can we actually at some point modulate the biologic aging process with or without help with from AI? So those are two very dense questions, but maybe you can take us through them.Charles Swanton (46:57):How long have we got?Eric Topol (46:59):Just however long you have.A.I. and CancerCharles Swanton (47:02):AI and cancer. Well, AI and medicine actually in general, whether it's biomedical research or medical care, has just infinite potential. And I'm very, very excited about it. I think what excites me about AI is it's almost the infinite possibilities to work across scale. Some of the challenges we raised in the Cell review that you mentioned, tackling, embracing complexity are perfectly suited for an AI problem. Nonlinear data working, for instance in our fields with CT imaging, MRI imaging, clinical outcome data, blood parameters, genomics, transcriptomes and proteomes and trying to relate this all into something that's understandable that relates to risk of disease or potential identification of a new drug target, for example. There are numerous publications that you and others have covered that allude to the incredible possibilities there that are leading to, for instance, the new identification of drug targets. I mean, Eli Van Allen's published some beautiful work here and in the context of prostate cancer with MDM4 and FGF receptor molecules being intimately related to disease biology.(48:18):But then it's not just that, not just drug target identification, it's also going all the way through to the clinic through drug discovery. It's how you get these small molecules to interact with oncogenic proteins and to inhibit them. And there are some really spectacular developments going on in, for instance, time resolved cryo-electron microscopy, where in combination with modeling and quantum computing and what have you, you can start to find pockets emerging in mutant proteins, but not the wild type ones that are druggable. And then you can use sort of synthetic AI driven libraries to find small molecules that will be predicted to bind these transiently emerging pockets. So it's almost like AI is primed to help at every stage in scientific investigation from the bench all the way through to the bedside. And there are examples all the way through there in the literature that you and others have covered in the last few years. So I could not be more excited about that.Eric Topol (49:29):I couldn't agree with you more. And I think when we get to multimodal AI at the individual level across all their risks for conditions in their future, I hope someday will fulfill that fantasy of primary prevention. And that is getting me to this point that I touched on because I do think they interact to some degree AI and then will we ever be able to have an impact on aging? Most people conflate this because what we've been talking about throughout the hour has been age-related diseases, that is cancer, for example, and cardiovascular and neurodegenerative, which is different than changing aging per se, body wide aging. Do you think we'll ever changed body wide aging?Charles Swanton (50:18):Wow, what a question. Well, if you'd asked me 10 years ago, 15 years ago, do you think we'll ever cure melanoma in my lifetime, I'd have said definitely not. And now look where we are. Half of patients with melanoma, advanced melanoma, even with brain metastasis curd with combination checkpoint therapy. So I never say never in biology anymore. It always comes back to bite you and prove you wrong. So I think it's perfectly possible.Charles Swanton (50:49):We have ways to slow down the aging process. I guess the question is what will be the consequences of that?Eric Topol (50:55):That's what I was going to ask you, because all these things like epigenetic reprogramming and senolytic drugs, and they seem to at least pose some risk for cancer.Charles Swanton (51:09):That's the problem. This is an evolutionary phenomenon. It's a sort of biological response to the onslaught of these malignant cells that are potentially occurring every day in our normal tissue. And so, by tackling one problem, do we create another? And I think that's going to be the big challenge over the next 50 years.Eric Topol (51:31):Yeah, and I think your point about the multi-decade challenge, because if you can promote healthy aging without any risk of cancer, that would be great. But if the tradeoff is close, it's not going to be very favorable. That seems to be the main liability of modulation aging through many of the, there's many shots on goal here, of course, as you well know. But they do seem to pose that risk in general.Charles Swanton (51:58):I think that's right. I think the other thing is, I still find, I don't know if you agree with me, but it is an immense conundrum. What is the underlying molecular basis for somatic aging, for aging of normal tissues? And it may be multifactorial, it may not be just one answer to that question. And different tissues may age in different ways. I don't know. It's a fascinating area of biology, but I think it really needs to be studied more because as you say, it underpins all of these diseases we've been talking about today, cardiovascular, neurodegeneration, cancer, you name it. We absolutely have to understand this. And actually, the more I work in cancer, the more I feel like actually what I'm working on is aging.(52:48):And this is something that James DeGregori and I have discussed a lot. There's an observation that in medicine around patients with alpha-1 antitrypsin deficiency who are at higher risk of lung cancer, but they're also at high risk of COPD, and we know the associations of chronic obstructive pulmonary disease with lung cancer risk. And one of the theories that James had, and I think this is a beautiful idea, actually, is as our tissues age, and COPD is a reflection of aging, to some extent gone wrong. And as our tissues age, they become less good at controlling the expansion of these premalignant clones, harboring, harboring oncogenic mutations in normal tissue. And as those premalignant clones expand, the substrate for evolution also expands. So there's more likely to be a second and third hit genetically. So it may be by disrupting the extracellular matrices through inflammation that triggers COPD through alpha-1 antitrypsin deficiency or smoking, et cetera, you are less effectively controlling these emergent clones that just expand with age, which I think is a fascinating idea actually.Eric Topol (54:01):It really is. Well, I want to tell you, Charlie, this has been the most fascinating, exhilarating discussion I've ever had on cancer. I mean, really, I am indebted to you because not just all the work you've done, but your ability to really express it, articulate it in a way that hopefully everyone can understand who's listening or reading the transcript. So we'll keep following what you're doing because you're doing a lot of stuff. I can't thank you enough for joining me today, and you've given me lots of things to think about. I hope the people that are listening or reading feel the same way. I mean, this has been so mind bending in many respects. We're indebted to you.Charles Swanton (54:49):Well, we all love reading your Twitter feeds. Keep them coming. It helps us keep a broader view of medicine and biological research, not just cancer, which is why I love it so much.******************************************The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informativeVoluntary paid subscriptions all go to support Scripps Research. Many thanks for that—they greatly helped fund our summer internship programs for 2023 and 2024.Thanks to my producer Jessica Nguyen and Sinjun Balabanoff tor audio and video support at Scripps Research.Note: you can select preferences to receive emails about newsletters, podcasts, or all I don't want to bother you with an email for content that you're not interested in. Get full access to Ground Truths at erictopol.substack.com/subscribe

We love to hear from our listeners. Send us a message.Dr. Marcus Conant is CMO at Addimmune, a biotech startup developing a cell therapy for HIV that spun out of cell and gene therapy biotech American Gene Technologies (AGT). He spent his career on the front lines of HIV treatment and research and remains an advocate for the HIV patient. He formed the Kaposi's Sarcoma Research & Education Foundation in 1982, which later became the San Francisco AIDS Foundation. On this episode, Dr. Conant shares they why behind cell and gene therapy to treat HIV, and he explains Addimmune's lead asset, AGT103-T, which is designed to provide broad protection using silencing RNA to inhibit binding/entry of the virus, halt replication, and prevent escape.

Frequency and anatomic distribution of lymphadenopathic Kaposi's sarcoma in the acquired immunodeficiency syndrome: An autopsy series - ScienceDirect

This week we talk about HIV, AIDS, and ART.We also discuss HAART, the Berlin Patient, and potential future cures.Recommended Book: Allergic by Theresa MacPhailShow Notes* https://www.unaids.org/en/resources/fact-sheet* https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-treatment-basics* https://clinicalinfo.hiv.gov/en/glossary/antiretroviral-therapy-art* https://www.paho.org/en/topics/antiretroviral-therapy* https://journals.lww.com/jaids/fulltext/2010/01010/declines_in_mortality_rates_and_changes_in_causes.13.aspx* https://link.springer.com/article/10.1007/s13181-013-0325-8* https://academic.oup.com/jac/article/73/11/3148/5055837?login=false* https://journals.lww.com/jaids/fulltext/2016/09010/narrowing_the_gap_in_life_expectancy_between.6.aspx* https://en.wikipedia.org/wiki/Tenofovir_disoproxil* https://en.wikipedia.org/wiki/Management_of_HIV/AIDS* https://www.verywellhealth.com/cart-hiv-combination-antiretroviral-therapy-48921* https://www.cdc.gov/hiv/risk/art/index.html* https://www.freethink.com/health/cured-of-hiv* https://www.jstor.org/stable/3397566?origin=crossref* https://www.nytimes.com/1982/05/11/science/new-homosexual-disorder-worries-health-officials.html* https://pubmed.ncbi.nlm.nih.gov/23444290/* https://my.clevelandclinic.org/health/diseases/4251-hiv-aids* https://web.archive.org/web/20080527201701/http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf* https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(23)00028-0/fulltextTranscriptIn mid-May of 1981, the queer community-focused newspaper, the New York Native, published what would become the first-ever article on a strange disease that seemed to be afflicting community members in the city.What eventually became known as AIDS, but which was at the time discussed by medical professionals primarily in terms of its associated diseases, was clinically reported upon for the first time less than a month later, five official cases having been documented in an interconnected group of gay men and users of injectable drugs, who came to the attention of doctors for not being inherently immunocompromised, but still somehow contracting a rare type of pneumonia that only really impacted folks with severely impaired immune systems.In subsequent years, doctors started using a range of different terms for HIV and AIDS, calling them at different times and in different contexts the lymphotophic retrovirus, Kaposi's sarcoma and opportunistic infections, and the 4H disease, referring to heroine users, hemophiliacs, homosexuals, and Haitians, the four groups that seemed to make up almost all of the confirmed afflicted patients.The acronym GRID, for gay-related immune deficiency was also used for a time, but that one was fairly rapidly phased out when it became clear that this condition wasn't limited to the gay community—though those earlier assumptions and the terminology associated with them did manage to lock that bias into mainstream conversation and understanding of AIDS and HIV for a long time, and in some cases and in some locations, to this day.By the mid-80s, two research groups had identified different viruses that seemed to be associated with or responsible for cases of this mysterious condition, and it was eventually determined (in 1986) that they were actually the same virus, and that virus was designated HIV.HIV, short for Human Immunodeficiency Virus, is a retrovirus that, if left untreated, leads to Acquired Immunodeficiency Syndrome, or AIDS, in about 50% of patients within ten years of infection.So HIV is the virus, AIDS is a condition someone with HIV can develop after their immune system is severely damaged by the infection, and there are a bunch of diagnostic differentiations that determine when someone has transitioned from one category to the other, but in general folks with HIV will experience moderate flu- or mono-like symptoms, alongside swollen lymph nodes and rashes and throat problems and sores across their bodies in the early stages of infection, and as things progress, they develop opportunistic infections of the kind that can only really latch onto a human when their immune system is weakened or shut down. While AIDS, arriving after the immune system is well and truly damaged, brings with it a slew of opportunistic infections and associated issues, the afflicted person potentially developing all sorts of cancers, sarcomas, persistent infections, and extreme versions of the flu-like, mono-like symptoms they may have suffered earlier on.We don't know for certain how and where HIV originated—and that's true of both kinds, as there's an HIV-1 and HIV-2 virus, the former of which accounts for most infections, the latter of which is less common, and less overall infectious—but both HIV types seem to have been transmitted to humans from non-human primates somewhere in West-central Africa in the early 20th century, possibly from chimpanzees in southern Cameroon, but that's pretty speculative, and there's some evidence that these diseases may have made the leap several times; so while there's a pretty good chance, based on what we know now, that the disease made it into humans and mutated approximately somewhere in that vicinity, sometime in the early 20th century, possibly via chimps hunted and eaten by locals as bushmeat, we really don't know for certain.There are reports of what were probably HIV as far back as 1959 in the Belgian Congo, but that's a bit speculative, too, and based on imperfect notes from the time.Back then, though, and through the 1980s, folks who contracted HIV and who were not treated would typically die within 11 years of being infected, and more than half of those diagnosed with AIDS in the US from 1981 through 1992 died within 2 years of their diagnosis; such a diagnosis was a death sentence, basically; it was a really horrible and scary time.Today, the outlook for folks who contract HIV is substantially better: the life expectancy of someone who contracts the virus and who is able to get treatment is about the same as someone who is not infected; the disease isn't cured, but the level of HIV virus in the blood of a person receiving treatment is so small that it's no longer transmissible, or even detectable.What I'd like to talk about today is a new therapy that's making those sorts of outcomes possible, how some few people have now been cured of HIV entirely, and what's on the horizon in this space.—Antiretroviral therapy, or ART, typically consists of a combination of drugs based on those that were originally combined in this way in 1996 by researchers who announced their findings at the International AIDS Conference in Vancouver—they called their approach highly active antiretroviral therapy, or HAART, and this combo was based on findings from earlier drugs that addressed one of HIV's seven stages of development—but because they all hit that same, single stage, the virus was rapidly developing an immunity to them, and they were universally pretty toxic, with horrible side-effects.What's more, this drug cocktail increased patients' life expectancy by about 24 months, on average—which is a lot, about two years, but considering all those side effects, which included severe liver problems and anemia, the extra months of life generally weren't very pleasant extra months.In 1995, a class of drugs called protease inhibitors were introduced, which prevented HIV from making copies of itself using the body's structural proteins.That, combined with the effects of other, existing retrovirals, which hindered the virus's ability to hijack the body's cells to make more of itself, turned out to be a substantial improvement over just one or the other approach.The announcement in 1996 was notable because the researchers involved were able to knock the viral load in their patients down to an undetectable level, and then keep it there, by using three drugs from each of those two antiviral classes, those two different approaches.So HAART was a major improvement over what came before, but it was still imperfect; deaths tied to HIV plummeted by 50% in the US and Europe in just three years, but the life expectancy of folks using this therapy was still low compared to other people; someone who contracted HIV in their 20s and went on this therapy was still only expected to live till their early 50s; way better than a two-year increase, but still plenty of room for improvement.In addition to that lifespan duration limitation, the HAART bundle of therapies was just really difficult to maintain.Some people experienced a dramatic redistribution of body fat, some developed heart arrhythmias or insulin resistance or peripheral neuropathy or lactic acidosis—which is basically a toxic buildup of the acid that results from metabolism, which is usually cleared naturally, but when it doesn't, it's potentially deadly.Anything less than absolutely perfect adherence to the treatment schedule was also potentially deleterious to the desired outcomes; it wasn't a forgiving regimen, with some of the drugs requiring three capsules be taken every 8 hours, and there was a chance that if a portion of a dose of one drug was missed, or not administered on time, the virus could develop an immunity to it and the whole thing would fall apart.Consequently, the HAART regimen was generally reserved until things got really bad, and that meant it didn't have a very large effect on the infected population, and those who did benefit from it suffered consequences, alongside those benefits.The change in terminology from HAART to ART arrived in 2001 when a drug called Viread, the brand name for tenofovir disoproxil, was released and added into the mix, replacing some of the most toxic and cumbersome of the previous therapies with a single pill per day, and one that came with far fewer, and far less extreme, side effects.In 2005 it was finally demonstrable, with a bunch of data, that beginning this type of therapy early rather than waiting until things get really bad was worth the trade-offs—researchers showed that if folks received access to ART upon diagnosis, severe HIV associated and non HIV associated illnesses  were reduced by 61%.As of 2016 there was still an average life expectancy gap between folks with HIV who received early care and people who were not infected of about 8 years, but that gap has been steadily closing with the introduction of new, easier to use, less side effect prone drugs—drugs that tend to attack the virus at different stages, and which take different approaches to hindering and blocking it—alongside innovations in how the drugs are delivered, like introducing substances that are converted by the body into the desired drug, which massively cuts the requisite dosage, in turn lessening the strain on the body's organs and the potential side effects associated with taking a higher dose of the drug, itself.We've also seen the advent of fixed-dose combination drugs, which are exactly what they sound like: a single pill containing the entire combination of drugs one must take each day, which makes a combination therapy much easier to administration and stick with, which in turn has substantially reduced the risk of severe side effects, and prevented mutations that might otherwise make a patient's virus more immune to some component of the drug cocktail.Some newer options just use two drugs, too, compared to the previous three-or-more, and most of these have been shown to be just as effective as the earlier, more bodily stressful combinations, and a recent, 2021 drug is injectable, rather than deliverable in pill-form, and can be administered just once a month—though a version of this drug, sold under the name Cabenuva, has been approved for administration every other month.So things in this corner of the medical world are looking pretty good, due new approaches and innovations to existing therapy models.These models remain imperfect, but they're getting better every year, and contracting HIV is no longer a death sentence, nor does it mean you'll always be infectious, or even detectably infected: the amount of HIV virus in one's blood can be kept undetectably low for essentially one's entire life, so long as one is able to get on the right therapy or combination of therapies and stick with it.That said, the global HIV pandemic is far from over, and access to these drugs–many of which are pricy, if you don't have insurance that will cover them—is not equally distributed.As of late-2022, the UN's official numbers indicate that about 39 million people, globally, have HIV, about 1.3 million were infected in 2022, and about 630,000 died from AIDS-related illnesses that year.That said, of those 39 million or so who are infected, nearly 30 million are receiving some kind of antiretroviral therapy, and about 86% of people who are estimated to be infected know their status, so they can seek such therapies, and/or take other precautious to protect themselves and others; though that also means about 5.5 million people, globally, have HIV and don't realize it.Here's a really remarkable figure, though: among people who are infected and know they are infected, about 93% of them were virally suppressed as of 2022.That's astonishing; 93% of people who have HIV and are aware of it are on some kind of therapy that has allowed them to suppress the virus so that it's nearly undetectable—the difference between the two, by the way, is that suppressed means 200 copies of the HIV virus per milliliter of blood, while undetectable is generally considered to be less than 50 copies per milliliter.So huge leaps in a relatively short period of time, and a massive improvement in both duration and quality of life for folks who might otherwise suffer mightily, and then die early, because of this virus and its associated symptoms.That said, there are some interesting, new approaches to dealing with HIV on the horizon, and some of them might prove to be even more impactful than this current batch of incredibly impactful ART options.As of September 2023, five people have been confirmed cured of HIV; not suppressed and not with viral loads at undetectable levels: cured.The first of these cured people, often referred to as the Berlin Patient, received a stem cell transplant from a bone marrow donation database that contained a genetic mutation called CCR5 Delta 32, which makes those who have it essentially immune to HIV infection.Three months after he received the transplant and stopped taking ART, doctors were unable to find any trace of the virus in his blood.He died from cancer in 2020, but there didn't seem to be any HIV in his blood from when he received the stem cell transplant, onward, and that happened in the early 2000s, and was formally announced to the medical community in 2008.At least two other people—two that we know about, anyway—have been cured of HIV using the same method; though at the moment at least, this option is severely limited as it requires that patients have a bone marrow match in donor databases, and that one of those donors have that specific, relatively rare mutation; so with existing science and techniques, at least, this is unlikely to be a widespread solution to this problem—though a 2017 experiment used stem cells derived from umbilical cord blood from a baby with that mutation to treat a woman' leukemia and cure her HIV, so there's a chance other approaches that make use of the same basic concept might be developed, opening this up to more people.Cancer drugs may also help some people with HIV: a drug that's been approved to treat several cancers called Venetoclax seems to also bind to a protein that helps HIV-infected T cells dodge the body's immune system and survive, and that realization has led to a series of experiments that showed HIV was suppressed in mice receiving this drug—though it bounced back a week later, and two weeks later in mice receiving both this drug and ART.This is unlikely to be a solution unto itself, then, but there's a chance either an adjusted version of this drug, or this drug in combination with other therapies, might be effective; and there's a clinical trial testing the efficacy of Venetoclax in human HIV patients at the end of this year, and another in 2024, so we may soon know if its safe and desirable to use this drug alongside ART, and that may, in turn, lead to a better understanding of how to amplify the drug's effects, or apply this method of hindering HIV from a different angle.CRISPR, the gene-editing technology borrowed from bacteria that allows for the cutting and removing and adding of genetic information, has enabled the development of several new potential HIV cures, one of which, called EBT-101, basically enters the body, finds helper T cells, and then cuts out chunks of the HIV virus's DNA, which prevents it from being able to replicate itself or hide away, reemerging later after another treatment has suppressed it.The benefit of this approach is that it could kill the viral reservoirs that otherwise allow HIV to persist in people who have undergone treatments, and a version of it that targets SIV, which is similar to HIV, but found in non-human primates—performed exactly as they hoped it would, finding and editing the targeted DNA, raising hopes than an HIV-targeting variation may manage similar wonders in human patients.This would be great if it ends up working, as one injection would theoretically clear all HIV from a person's system in relatively short-order, but the trials done so far have been small and on monkeys, and because of the nature of the research, it's not clear the monkeys were cured of HIV—just that the treatment got where it was supposed to go and made some DNA edits.A human trial of EBT-101 will finish up in March of 2025, though the researchers plan to follow up with their subjects for up to 15 years following the trial, to assess any long-term effects from their treatment, since CRISPR and this approach to messing with genes is still such a new thing.So while this may be a solution at some point, there's a good chance it won't be a real-deal, available option for another decade, minimum.So we've come a long way in a very short period of time with HIV and AIDS treatments, and the future is looking pretty good, with even more options and approaches on the horizon, including some actual cures, alongside high-quality, actually useable treatments.But there's still room to grow in terms of infection awareness, there are still distribution issues for some of these drugs, and there's still a fair bit of prejudice, the consequence of ignorance and historical misunderstandings and biases, keeping folks and institutions from doing as much as they otherwise could in many parts of the world; so a lot to be proud of, a lot to look forward to, but still plenty of room for improvement across the board. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit letsknowthings.substack.com/subscribe

Dr. Ana Velez, Professor of Medicine and Infectious Diseases Clinician at Moffitt Cancer Center and Research Institute, discusses the association between malignancies and Human Immunodeficiency Virus Infection. Dr. Velez begins by discussing that factors in HIV disease and stimulate the formation of cancers. Next, Dr. Velez discusses AIDS defining maligancies, including Kaposi sarcoma, Non-Hodgekin Lymphoma, and cervical cancer. Dr. Velez then discusses lung cancer and head and neck cancer in HIV disease, and speculates on the reasons for poorer outcomes in these patients. Lastly, state of the art therapies for malignancy treatment in HIV patients are discussed, including stem cell transplantation and CAR-T therapy.

In this JCO Article Insights episode, Davide Soldato interviews Dr. Naqash  from University of Oklahoma. Dr. Naqash provides insight into the original article published in the July JCO issue: “Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium”. The interview offers a deep dive into the manuscript results on efficacy and safety of Immune Checkpoint Inhibitors in this specific population and offers insights on future research direction in this space. TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Davide Soldato: Welcome to this JCO Article Insights episode for the July issues of JCO. This is Davide Soldato and today I will have the pleasure of interviewing Dr. Abdul Rafeh Naqash, the author of the manuscript titled "Safety and Activity of Immune Checkpoint Inhibitors in People Living with HIV and Cancer: A Real World Report from the Cancer Therapy Using Checkpoint Inhibitors in People Living with HIV-International Consortium."  Dr. Naqash is an Assistant Professor of Hematology-Oncology at the University of Oklahoma and a Medical Oncologist working at the Stephenson Cancer Center. His research interests revolve around early-phase clinical trials in solid tumors, lung cancer, and the study of immunotherapy, biomarkers, and resistance.  Welcome, Dr. Naqash, and thank you for accepting our invitation today. Dr. Abdul Rafeh Naqash: Dr. Soldato, thanks so much for having me. I'm really excited to discuss this article with you today. Davide Soldato: So I just wanted to go a little bit over the manuscript with you. So basically, this is a retrospective multicenter study that was conducted across the US, Europe, and Australia by the CATCH-IT Consortium. And so the aim of the study was really to investigate the safety and the activity of immune checkpoint inhibitors among patients diagnosed with cancer and also living with HIV. The article examined two different cohorts, and I just wanted to start with a brief explanation of how the two cohorts were built so that our readers can get a little bit of understanding of what you did then. Dr. Abdul Rafeh Naqash: Sure. Before I take a deep dive into the cohorts, Dr. Soldato, I would definitely like to mention the premise and the background for this paper as to why we did what we did. And one of the primary reasons was that people living with HIV, historically, there have been very limited number of trials that have included these individuals. So it becomes a very important question from a disparity standpoint. And most often we end up, in the real world setting, we end up extrapolating data from clinical trials, but not necessarily know what is the outcome of these individuals in the real world setting.  So there have been some very important studies in the last three years or so in people with HIV as far as clinical trials with checkpoint inhibitors go, but most of those trials have been limited by the number of patients, number of people that have been part of those trials. So we wanted to understand it from a broad perspective, whether it is from a broad geographic perspective or from a heterogeneous patient population perspective, which is why we built this consortium called the CATCH-IT Consortium, which basically stands for Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International Consortium. And this required a lot of effort from a lot of different centers, including those in the US, Europe, and Australia, as you mentioned. And then we ended up having data worth around 400 plus patients, close to 400 patients or so. And then we wanted to look at obviously outcomes, whether it's related to a certain tumor such as lung cancer, which we did in this case, or a pan tumor assessment of toxicities and safeties.  So, to your question, the cohorts that we basically had, we had close to approximately 390 patients that we included in the safety analysis. So first we looked at the safety analysis, which was the entire cohort, and then out of those we excluded around 12 patients or so. Those were patients that were treated in the adjuvant setting. So in the metastatic advanced setting, we had close to 378 individuals that we assessed clinical outcomes for. So, response rates, progression-free survival, and overall survival. And then as far as a separate cohort, we looked at non-small cell lung cancer, which was the most commonly represented tumor type, with approximately 111 patients that had non-small cell lung cancer. We did exclude a certain proportion of those that were earlier stage, stage III.  So in the stage IV, basically we ended up matching in this separate cohort, around 60 odd patients or so of non-small cell lung cancer to 110 stage four, non-small cell lung cancers. So basically it was a one-to-two matching and we chose the same site. So if a site had, let's say, two people with HIV and lung cancer treatment checkpoint, we tried to match it to approximately four to five patients from the same site and we used some variables for matching so that we had some level of homogeneity between the HIV patient population and the non-HIV positive lung cancer individuals. So that's basically cohort A was around 370-something patients, tumor agnostic advanced metastatic setting. Cohort B was lung cancer individuals matched to non-HIV positive lung cancer treatment checkpoint inhibitors. Davide Soldato: Thank you very much. That was very clear. Just to go back to what you were saying before because I think that this is very interesting. You mentioned that patients living with HIV were mostly excluded from clinical trials and in the few that included them, there were some restrictive criteria in terms for example of CD4-positive cells in the blood. And so I was wondering if when you included the patients inside of this cohort, you also had this type of exclusion criteria or you chose a broader population to make the results more generalizable and applicable in clinical practice.  Dr. Abdul Rafeh Naqash: Right, a very important question. Thank you, Dr. Soldato. So yes, previous clinical trials have had some level of restrictions as far as the inclusion of these individuals, but in our study, this was a real-world study, basically, patients whoever presents to the clinic with a history of HIV, they were all included. So we did not restrict it to certain CD4 counts or viral loads because the important thing was we wanted to understand the ground situation of how these individuals do, irrespective of some of these limitations. As far as what we identified as baseline CD counts or HIV viral load positivity, we took three months before immune checkpoint initiation as a cut off so obviously there's a limitation there. We didn't have results of these CD4, CD at a viral load assessments done like the day of or the week before in some patients. So we took three months and we included individuals that had received at least one or more dose of immune checkpoint therapy between January of 2015 to October of 2021, which was our database lock.  And then obviously the regimens included immune checkpoint anti-PD1, PD-L1 monotherapy, or in combination with other anticancer agents including anti-CTLA-4 or chemotherapies targets, which is important to point out here. So the trials that have been mostly done in this space are single-agent checkpoint inhibitors or anti-PD1 with anti-CTLA-4. There's not much data for immune checkpoint inhibition combined with other agents such as targeted therapies, chemotherapies. So we had some of that data in this cohort, which kind of made it interesting. Davide Soldato: Yeah, I think that it's very interesting and it's very wise to choose very broad eligibility criteria for these type of studies because it really answered to the question that we identified and that we spoke about in the beginning.  So going back to the results, you said that the cohort A, so the one that included all the patients, irrespectively of the type of tumor that was diagnosed, it was mainly for evaluating what was the safety of immune checkpoint inhibitors in patients living with HIV and with a concurrent cancer diagnosis. So I was wondering if in this cohort you identified some differences compared to historic data in terms of, for example, incidence of grade three or higher toxicities or incidence of immune-related adverse events in general, and if maybe there was some adverse events that was very characteristic or particular in this cohort. Dr. Abdul Rafeh Naqash: So immune-adverse events is a very interesting question not only from this cohort but in general because it overlaps with this question of autoimmunity and cross T cell cross reactivity. And this is a unique patient population where we have the ability, although not fully but to some extent, to look at the role for CD counts and also look for patterns of adverse events.  To answer your first part of the question, we didn't see any significant differences for the types of adverse events. We did see the incident was a little lower than what you would expect in the real-world setting for non-HIV individuals. Whether that has something to do with how the immune system is constructed in these individuals, nobody knows. We did look at CD4 and CD8 counts. As far as absolute CD4 counts, about 200 or below 200, we didn't see a difference as far as the cumulative incidence for immune checkpoint inhibitor-related adverse events. When we did a ratio of CD4 to CD8 of greater than 0.4 and compared it to less than 0.4, we did see that at around 24 weeks, there was a difference in terms of the cumulative incidence for adverse events. It was around 10% versus 26% when we use that cut-off of 0.4, suggesting that there might be some role of how the peripheral immune system results in the related adverse events in these individuals, but it's a very important question.  I think there are ongoing evaluations that are being done from other prospective studies that had collected blood samples in these individuals. But generally, we saw the same range of adverse events, diarrhea, colitis, pneumonitis, hepatitis. We did have a few patients who had  a history of opportunistic infections, but we didn't see any significant reactivation there which was part of the safety assessment in our analysis.    Davide Soldato: So basically, because I think that in HIV patients, even if those included in the study were almost all were on antiretroviral therapy, but you didn't observe any opportunistic infection that developed during the course of immunotherapy. Dr. Abdul Rafeh Naqash: You're absolutely right, we did not. In fact, we are trying to look at that in a different setting, in a different cohort because there have been some data on mycobacterial reactivation in individuals in general, not just HIV, but in our cohort of 400 odd patients, we did not see any new opportunistic infections. Davide Soldato: I think that one aspect that pops into my mind right now is also that we have kind of some data regarding also possible HPV reactivation in these types of patients treated with immune checkpoint inhibitors. So maybe that could be also something that you would be interested to look at in the future, I imagine.  Dr. Abdul Rafeh Naqash: Yes, we are planning to look at HPV-driven cancers actually for starters, anal and head and neck. We are also looking at hepatitis B-related HCC in a separate ongoing cohort. So there are definitely subsequent steps that we are currently involved in as far as viral-driven cancers and concurrent HIV is concerned. Davide Soldato: Thank you. I think that's very interesting. And I was wondering, you mentioned in the beginning that this patient clearly they have some degree of immune dysregulation or at least some type of dysfunction in terms of immune presentation and immune activation. So I think that one of the concerns or one of the worries of using immune checkpoint inhibitors in this population could also be that the efficacy that we see in patients that do not have HIV could be lower. Could you comment on this if you found any differences both in the cohort including all cancer, but also in the cohort B, that I think you had the strategic idea of pairing these patients living with HIV with patients that were not living with HIV. So I think that this brings very important data to the space. Dr. Abdul Rafeh Naqash: Yes, we tried to look at this one from a tumor-agnostic perspective and a tumor-specific perspective. So the tumor agnostic perspective was looking at a different set of cancers which included skin cancer, melanoma, lung cancer, non-Hodgkin's lymphoma, small cell head and neck, and a couple of other cancers. And one of the things we noticed was that there was a trend, so there was differential efficacy as far as the cancer type is concerned. So for example, skin, Hodgkin's lymphoma, Kaposi sarcoma, melanoma had the highest response rates, somewhere in the range of 60s to 40s. On the other hand, viral-driven cancers such as anal cancer, HCC, head and neck actually had very low response rates, less than 15% or so. So that begs the question of what is going on and we don't necessarily know, which is why we are trying to concentrate on the viral-driven cancers first. Because as you know, melanoma, Kaposi's do have historically shown better responses to checkpoint inhibitors.   Now do we know if when we compare these responses or survival to non-HIV individuals in clinical trials, are the outcomes similar? I would say in some of the tumor types the outcomes were somewhat inferior and in some of the tumor types the outcomes were somewhat similar. So for example, lung, we did compare non-small cell lung cancer. As I mentioned, we had two cohorts, we matched it to a non-HIV cohort and there we looked at progression-free survival and overall survival. And again the caveat is that this is a retrospectively matched cohort, this is not a prospectively matched cohort. So these are individuals that are not matched for each and every variable. They're matched for certain top three or four variables as much as we could accommodate. And based on that we didn't see a difference in the progression-free survival and the overall survival when we did an assessment.  In fact, we looked at it at a 42 month period where we looked at the restricted median survival time and it was not different, was around 17.8% for people with HIV and 18.4% for people without HIV as far as progression-free survival, and around 42% and 41% overall survival at the two-year mark. So basically there is not much significant difference which reiterates the fact that in the right setting, these individuals could be safely treated with immune checkpoint inhibition and could perhaps have similar outcomes. Maybe not in all tumor types, but in some tumor types. But at the end of the day, and we mentioned this in our manuscript also in subsequent work that we are trying to do, we have emphasized on the fact that it has to be a multidisciplinary discussion between the patient, the physician, the medical oncologist, the treating oncologist, and the infectious disease person. Because these individuals have a lot of complicated aspects because of the underlying HIV and taking that into perspective and then assessing risk-benefit is an important discussion.  So the goal of this work was not to establish that immune checkpoint inhibitors are absolutely beneficial or absolutely safe. The goal was more to create awareness that people in the real-world setting actually can benefit, which the next step would be to have more trials and perhaps modify inclusion criteria in clinical trials so that you can have a more inclusive approach, including these individuals.  Davide Soldato: Coming back to the multidisciplinary approach because I think that this is very interesting and should be really implemented when we have this type of patient. From the data that you collected, did you add any indication that maybe this patient treated in the real-world setting were not managed in such a multidisciplinary way? Dr. Abdul Rafeh Naqash: The easiest way to point that out is that most of these people or many of these individuals did not have HIV viral loads or CD4 counts done before treatment initiation. And that's an indirect surrogate for telling you that these are things that should have been thought of, but were not thought of if the individual taking care of these people either did not have expertise as far as HIV is concerned or did not have a colleague on the infectious disease side who was actively managing these people.  So that's an important indirect way where we kind of got a sense that there has to be more awareness about multidisciplinary care. And especially the immune adverse event situation in these individuals can get complicated because of the way their immune system is constructed and having that multidisciplinary care is very important. We didn't specifically collect data on what teams or what subspecialists were involved in each individual's care, but I think that would be an important assessment for maybe a future quality improvement project to look at why or how some of those things were not done so that it can lead to future improvements. Davide Soldato: So, just expanding on that, you said that you didn't have much data in terms of CD4 cells or in terms of viral load. But for what you had inside of your cohort, did you see any modification of these parameters that we know that are very important in patients living with HIV under immune checkpoint inhibitors therapy? Dr. Abdul Rafeh Naqash: Again, a very important immunological question, I think as far as what we saw- so we had close to around 74, 75 individuals that had CD4 T cell counts available. And we didn't see differences between baseline and post-immune checkpoint therapy changes in CD4 counts. Similarly, we didn't see a difference as far as HIV viral load and we had HIV viral loads present in around 107 individuals and we didn't see a difference. Now, again, 30% of our cohort was CD4 count less than 200, and 70% was CD4 count more than 200, , which is again, important to highlight because many trials don't take individuals with the CD4 count less than 200. But in general, we did not see a difference in this pre and post-assessment both for viral load and both for CD4 count. Now trials in this space have ongoing assessments that they are doing. The AIDS Malignancy Consortium does have a trial looking at changes in CD4/CD8 counts or viral loads. In fact, the CITN trial which is a pembrolizumab trial published a couple of years back did have an assessment done as far as CD4 counts and viral loads are concerned. And I think they did see a slight increase in the CD4 counts and there are some aspects about how the immune system may change with an immune checkpoint inhibitor. But I think the strength of the data is not that much, and I think we probably need more patient samples to assess why or how some of that could change or what implications it would have for patients.  Now, there is another concept of HIV viral latency removal that some of the listeners might have heard of, especially in the HIV setting, where you were given an immune checkpoint inhibitor and it can lead to reversal or reduction of the HIV reservoir, which can somehow impact the CD4 counts, and also lead to elimination of the viruses through CD8. But again, that's a more complicated assessment and we didn't have data for it.   Davide Soldato: Thank you very much. That was very interesting also for future perspectives in this topic.  I just wanted to ask you if the idea for the research came more from ensuring equity in terms of care delivery for patients living with HIV or if it was more also to investigate the immunological components that we discussed just as far or a good mix of the two. Dr. Abdul Rafeh Naqash: I think the idea actually stemmed from this individual who's the first author, Dr. Talal El Zarif and co-first author Dr. Amin Nasser from Dana-Farber, reached out a year and a half back and they wanted to look at outcomes from an HIV standpoint and see what the real world setting is. And the goal was they would have their data and we would have our data and we would eventually collect the data together or combine the data together. But then after some conversations, we started looking at the available data, the available literature, saw that there was a decent gap in what we know. And I know there are some brilliant groups in the HIV space, especially at the NCI. In fact, Dr. Kate Lurain and Dr. Ramaswami are good collaborators of ours and they worked in this space and are currently developing trials in this space. But it just did seem like this would be a more interesting approach of answering a real-world question and then also looking at the disparities of it because as an early-phase drug development trialist, I still see a lot of trials, in fact, majority of the trials, say people with HIV or history of HIV are excluded.  Now, the NCI has made important efforts in that space of including those individuals, but I think we still have some ways to go. So basically the idea came from two trainees who were extremely enthusiastic and wanted to pursue this. And I, obviously, seeing their level of enthusiasm and excitement, I was excited too. And then importantly, if you look at the paper, we have a bunch of authors, we have close to 79, 80 authors on that paper. And the primary reason was that each center contributed in certain ways, including patients' data and then expertise. And this ended up being a huge community effort from the oncology community, where everybody's individual effort led to something like this coming to fruition.  So it was a multitude of different aspects, but yes, it all started with a question of how these individuals do and the current data where they're missing gaps, and we wanted to sort of supplement those gaps and provide insights using this important real-world data set. Davide Soldato: Thank you very much for the insight on how the idea came to be.  Is there anything else you would like to add or to summarize for our listeners? Dr. Abdul Rafeh Naqash: Well, first of all, I appreciate the opportunity to discuss our paper here. I would like to thank you and of course the JCO staff for organizing this, and also the JCO Journal for giving us the opportunity to publish this important work. Some of the things that we would like to highlight as outcomes from this paper, as we sort of discussed, but to summarize those: we saw that we didn't have any significant safety concerns, obviously. We saw that some patients in certain tumor types do benefit, similar to what you might expect in a non-HIV setting in the real world as well.  And of course, this was the largest real-world data set of people with HIV and cancer. And we have ongoing efforts in different directions, as I mentioned to you. And we are more than happy to collaborate with anybody who has good ideas because this is a community-level data set. It was created for the community, by the community, and the goal is to utilize this data set. So if there is a listener out there who's interested in collaborating, who has an idea, we're more than happy to share the data set in the right setting. And then hopefully, everybody has the opportunity to lead different efforts in the space. Davide Soldato: Thank you again for being with us today, Dr. Naqash. To hear more from Dr. Naqash, please check out ASCO's JCO Precision Oncology Conversation Podcast.  So this is Davide Soldato. In this episode of JCO Article Insights, we discussed the results of the manuscript titled, “Safety and Activity of Immune Checkpoint Inhibitors in People Living with HIV and Cancer: A Real World Report from the Cancer Therapy Using Checkpoint Inhibitors in People Living with HIV-International Consortium.” Thank you for your attention and stay tuned for the next episode.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Herpesvirus comes in many forms. Eight types of herpesviruses can infect people and after the initial infection, all herpesviruses tend to remain dormant in your body until they can eventually reactivate. Herpes Simplex Virus (HSV I&II) Epstein-Barr Virus, (EBV), Cytomeglavirus (CMV), Kaposi's Sarcoma (Herpesvirus 8 a form of cancer) are some of the most common types. Despite the fact that the herpesviruses are structurally and genetically similar, they cause a wide variety of clinical reactions. ALL of them have psychologically, socially and emotionally wrecked peoples lives! Is there a cure? YES! Direct Intravenous Ozone Therapy has proven to be able to do it when used in special protocols. We will discuss these viruses, howe they affect your body and what you can do to eliminate them, permanently, completely, once and for all!

Herpesvirus comes in many forms. Eight types of herpesviruses can infect people and after the initial infection, all herpesviruses tend to remain dormant in your body until they can eventually reactivate. Herpes Simplex Virus (HSV I&II) Epstein-Barr Virus, (EBV), Cytomeglavirus (CMV), Kaposi's Sarcoma (Herpesvirus 8 a form of cancer) are some of the most common types. Despite the fact that the herpesviruses are structurally and genetically similar, they cause a wide variety of clinical reactions. ALL of them have psychologically, socially and emotionally wrecked peoples lives! Is there a cure? YES! Direct Intravenous Ozone Therapy has proven to be able to do it when used in special protocols. We will discuss these viruses, howe they affect your body and what you can do to eliminate them, permanently, completely, once and for all!

Herpesvirus comes in many forms. Eight types of herpesviruses can infect people and after the initial infection, all herpesviruses tend to remain dormant in your body until they can eventually reactivate. Herpes Simplex Virus (HSV I&II) Epstein-Barr Virus, (EBV), Cytomeglavirus (CMV), Kaposi's Sarcoma (Herpesvirus 8 a form of cancer) are some of the most common types. Despite the fact that the herpesviruses are structurally and genetically similar, they cause a wide variety of clinical reactions. ALL of them have psychologically, socially and emotionally wrecked peoples lives! Is there a cure? YES! Direct Intravenous Ozone Therapy has proven to be able to do it when used in special protocols. We will discuss these viruses, howe they affect your body and what you can do to eliminate them, permanently, completely, once and for all!

Today on the show we welcome Dr. Marcus Conant, chief medical officer of American Gene Technologies. Dr. Conant was one of the first physicians to treat AIDS in San Francisco while running the inpatient dermatology service at the University of California San Francisco. Before anyone recognized the virus or understood that it was about to become a global epidemic, Dr. Conant took the lead in forming the Kaposi's Sarcoma Research & Education Foundation in 1982, which later became the San Francisco AIDS Foundation. He's dedicated much of his career to fighting for an end to HIV.Full bio Marcus A. Conant, MDChief Medical Officer at American Gene TechnologiesMarcus A. Conant, MD is a physician who treated thousands of HIV patients in the early 80s while running the inpatient dermatology service at the University of California San Francisco. Before anyone recognized the virus or understood that it was about to become a global epidemic, he took the lead in forming the Kaposi's Sarcoma Research & Education Foundation in 1982, which later became the San Francisco AIDS Foundation. Marcus conducted early clinical trials, persevering despite seeing 94% of patients die during the epidemic's first years. His clinical experience sensitized him to the suffering caused by the disease. As a physician with a holistic perspective, his work expanded beyond the strictly clinical, to include education, research, and advocacy. Marcus is currently a clinical professor emeritus at the University of California Medical Center in San Francisco. He has published more than 70 articles on the treatment of AIDS, testified in front of Congress multiple times, and is a powerful advocate for the LGBTQ community.LinksMarcus Conant, MD, LinkedIn: https://www.linkedin.com/in/marcus-conant-056699229/American Gene Technologies Website: https://www.americangene.com/American Gene Technologies LinkedIn: https://www.linkedin.com/company/1127234/American Gene Technologies Facebook: https://www.facebook.com/amerigene/American Gene Technologies Twitter: https://twitter.com/americangeneAmerican Gene Technologies Instagram: https://www.instagram.com/americangenetechnologies/Qualio website:https://www.qualio.com/ Previous episodes:https://www.qualio.com/from-lab-to-launch-podcast Apply to be on the show:https://forms.gle/uUH2YtCFxJHrVGeL8 Music by keldez

Listen to ASCO's Journal of Clinical Oncology essay, “First Cousins Once Removed” by Dr. Matthew Farrell, a radiation oncology resident at UCLA. The essay is followed by an interview with Farrell and host Dr. Lidia Schapira. Farrell paints scenes of how different family dynamics can come into play when advocating for patients. TRANSCRIPT Narrator: First Cousin Once Removed, by Matthew J. Farrell, MD, MFA (10.1200/JCO.22.02611)  When I was a kid, long before I wanted to be a doctor or had even heard of oncology, I dreamed of becoming an actor. I grew up in Sacramento—not exactly the beating heart of the film industry—but my mother's mother lived in Santa Monica and we would stay with her for a month every summer. My father would unashamedly sneak me into movie premieres in famous theaters, and he bought us season passes to Universal Studios Hollywood. Despite having a serious job—as a psychologist in the emergency department—he was a kid at heart. Los Angeles was our promised land, and our shepherd was my father's cousin John, my first cousin once removed, who lived in West Hollywood and was a living, breathing actor.  John wasn't famous, not yet. He was in his late 20s, just starting out, doing mostly background work and some commercials while working as a waiter at the original Cheesecake Factory in Beverly Hills. All the staff loved him there, so much so that they would give us free pieces of cheesecake just for being related to him. John was generous, outgoing, expressive, and talented. Success seemed just around the corner.  One challenge for him was his voice. He had a thick Bronx accent, which would have been perfect if he had been auditioning for Raging Bull but which otherwise narrowed his prospects. He hired a voice coach to help him erase his accent. But that didn't mean he was trying to erase his New York roots. He was proud of his upbringing and family, coming from a long line of police officers, burly men with strong jaws and thick arms and outdoor voices who seemed to be the very genesis of their own stereotype. And as his Bronx accent faded, he was teaching it to me. He said he would take me to a baseball game at Yankee Stadium one day, and he imitated the beer hawkers who walked up and down the aisles, calling out to the crowd, “Get your beer here,” but pronounced, “Getcha bee-ah hee-ah!” John was the first person I distinctly remember being in perfect shape. He was a sight to behold—muscular and solid, yet graceful and light on his feet. In addition to being an actor, he was training as a dancer. Coming from generational athletic ineptitude myself, I was enthralled. He taught me how to moonwalk and do bicep curls. I would walk up to my mother and flex my tiny muscles, imagining a day when I would be as strong as John. One summer, John was much thinner—his face hollowed out, his previously bulky arms as lean as my own. What I only vaguely understood at the time was that he was gay, and he now had AIDS. This was the mid-1990s, and highly active antiretroviral therapy was on the horizon but just out of reach.1,2 His treatments failing him, he became desperate for a cure. He did twice daily coffee enemas, choked down repulsive herbal concoctions, and visited New Age visionary healers. For a long time, he remained optimistic. He was in constant contact with his agent, seeking out auditions even as his strength waned. He wasn't only a waiter at The Cheesecake Factory and he wasn't dying of AIDS; he was an actor who was going to be healthy again soon. Occasionally he would call my dad, buoyant with hope, “The virus is gone. I'm cured.”  Of course, he wasn't. My father never tried to talk John out of pursuing alternative therapies, though he considered doing so many times. The frantic search for a reprieve from death can take us many places, and it is not to be pitied. But how do you also protect your loved ones from harmful remedies and predatory scam artists? How do you provide the best treatment when there is no good treatment? In all my years, all 10 of them, I had thought that doctors knew everything, and if you went to them, you would get better. But John wasn't getting better. Together with his doctors, we embraced helplessness.  His CD4 count fell to zero. He developed skin lesions from Kaposi sarcoma. He was repeatedly hospitalized with Pneumocystis pneumonia. His organs began failing. Ultimately, he decided to leave the hospital on hospice. It was only then that he told his parents he was gay and had AIDS. At first, his parents couldn't believe he was gay. They told my father it was a phase, possibly brought on by his living in Los Angeles, a side effect of being an actor and dancer. Later, at his memorial service in New York, they would tell everyone he had died of a rare cancer. My father remembers someone asking John's mother what kind of cancer it was, and she said, “I don't know. It's very rare.”  During my winter break from school, my family visited John in his apartment. By that time, he had needed to quit his job at The Cheesecake Factory and stop taking auditions. His friends at the restaurant had thrown him a party and still came by his apartment most days. He lay in bed, drowsy and mildly delirious, too weak to stand. Even in this state, he kept trying to sit up to get us something to eat or drink. “I have cheesecake,” he said several times. “Let me get you some cheesecake.” Just a week later, on the day after Christmas, John lost consciousness. His kidneys weren't making urine, and he was uremic. My father urgently updated John's family in New York. His mother, father, and three sisters with their husbands flew in that day and crowded into John's small West Hollywood apartment.  For the first time, they met John's partner, Kevin, and five of their friends, gay men who had taken turns caring for John to make sure he was comfortable and never alone. Kevin was tall, elegant, and gentle. He was as introverted as John was extroverted, and he wouldn't have been caught dead on stage in front of an audience. He ran his own successful small business and had a quiet self possession. John, though he rarely showed it, was insecure about his slow progress in the acting world, and I think Kevin helped him feel more at ease. As a medical professional and the closest relative on the West Coast, my father had served as the point person for the hospice physician. He reported the latest news: John likely had just hours to live. John's New York family, previously shielded by distance, was caught off guard. And there was an uproar. The five stages of grief multiplied to 25, occurring in no discernible order—undulations of shouting and crying and jostling that rolled through the group like The Wave through a baseball crowd. At first, they wanted to take him off hospice. They looked ready to carry him out the door to the nearest hospital. They said his decline was too sudden. It just wasn't right. There must be something he hadn't tried. For every desperate hope they volleyed, my father sensitively explained what could and could not be done, and, more importantly, he described John's wishes. They gradually realized that saving him was impossible, and not what John needed anymore. At last, everyone seemed on the same page. Everyone but John. Day by day, he held on in his unconscious state, not crossing that final threshold, as if something were holding him back. John's family became increasingly exhausted, confused, and frustrated. They couldn't eat or sleep. On day four of John's marathon survival, we called in the hospice nurse. By this time, my grandfather—John's uncle— had also arrived. The nurse gathered everyone together and explained that it was often helpful to talk to your loved one, conscious or not, to say goodbye. People who are dying may feel obligated to cling to life for their family's sake. They may need our permission, even our encouragement, to let go.  And so, one by one, we all entered John's bedroom, knelt beside him, and said what we needed to say. And then, it was my grandfather's turn. By way of introduction, Grandpa Joe, my father's father, was raised in the Bronx by a stern mother and career soldier father. He was a businessman by profession and by religion. He rose in the ranks of multiple companies, eventually becoming the president of Hires Root Beer, a company that expanded during his tenure but was eventually bought by Orange Crush, which in turn crushed Hires Root Beer and made a lifelong enemy of my grandfather. (In my family, we do not drink Orange Crush.) Grandpa Joe never surrendered without a fight.  Accompanied by my father and me, Grandpa Joe marched up to John's bed and bent down beside him.  “You can fight this!” he said, shaking his fist. “I've had illnesses all my life and I came out on the other side. Did I let prostate cancer beat me? Hell no!” “Wait, Dad,” my father said. “Wrong plan.” “What?” Grandpa Joe said. “We had a whole conversation about this.” “When?” “Just now, with the hospice nurse. We need to let go, allow John to pass on.” “That's not what I heard.” “That's becoming clear to me.”  My father reviewed the plan, slowly, but no matter how well you explain yourself, sometimes people hear only what they're capable of hearing. Grandpa Joe couldn't surrender. He argued and fumed, eventually stormed out. So my father said goodbye for him. That night, John died.  I doubt the timing of his death was related to our collective send-off, but it sure felt like it was, and that will do. The next day, everyone assembled in John's apartment for the last time to decide what to do with his body. The family wanted to take him back to New York for a traditional burial.  But there had been talk that John's Los Angeles friends were planning to have him cremated. As if about to face off, two groups formed in opposing semicircles of folding chairs—the family seated on one side, and Kevin and his friends on the other. John's father, Hank, seemed ready to fight, his whole family there to back him up. Grandpa Joe kept saying we needed to put John on a plane and get him out of there.  In medical school, we learn that not all family members are created equal; when patients can't make decisions for themselves and there is no living will, you turn to the spouse first, adult children next, then parents, and so on. There is even a mnemonic (one of the clunkiest in existence) to help you remember the ranking: the Spouse ChiPS in For the patient—indicating Spouse, Child, Parent, Sibling, and Friend, in that order. Following this rule, Kevin would have come last. He and John weren't married, and gay marriage wasn't even legal then. My father, a child of the sixties, wasn't a fan of hierarchies. As a psychologist in the emergency department, he had always strived to foster a unanimous meeting of the minds and hearts. To make things a little easier on people like him, he says it is never too early to tell anyone and everyone what you want in life and in death. Then, importantly, write it down, in an advance directive, on a POLST form, and maybe even on a few napkins scattered throughout the house. Hank fired the opening salvo: he told Kevin that they were going to take John back to New York. Their community expected a traditional burial, needed it.  Kevin listened quietly until Hank finished. With a softspoken grace, he looked Hank in the eyes and told him he would never do anything against the family's wishes. If they wanted a burial in New York, he would help carry the casket. But, he said, John had told him many times that he wanted to be cremated and have his ashes scattered on Maui, at a certain overlook they had visited together. There was a long silence. Hank looked around, at his wife and family, at Grandpa Joe, all of whom seemed to be waiting for him to deliver their counterpunch. But then he lowered his head. He started crying into his hands.  A minute passed, and then he sat upright, sniffed, and nodded. In a clear, firm voice, he said, “That's it. That's what I want for John. I want you to take him to Maui.” In perhaps the only true miracle I have ever personally witnessed, Kevin and his friends lifted from their chairs in perfect unison, crossed the small living room, and flooded the family with hugs. Everybody cried, and the many headed beast of our congregation dissolved into a sea of affection. Kevin did go to Maui to scatter John's ashes. Afterward, John's family celebrated his life with a memorial service at their church in New York. My father gave the eulogy and Kevin sat with the family. All of this was a long time ago now. John would be in his fifties. He would have mastered a Hollywood accent. His big break would have come. He would have taken me to the Oscars. I moved away from California to go to graduate school and medical school, but eventually, I found my way back to Los Angeles. I still go to iconic theaters. I finally bought season passes to Universal Studios Hollywood. And like everyone else in this town, I'm trying to write a screenplay. But I'm not an actor. I'm not remotely famous. I'm a radiation oncology resident.  I've learned a few things since the 1990s, and so has the rest of the world. It still devastates me that John just missed the major advances in care. I think about him regularly during my training. In oncology, life-prolonging breakthroughs are frequent, which inevitably means that some people will be among the last to miss out. Some people, and their families, will look to me for hope when there is none. In their entreaties, I see shades of my own loved ones—my father's diplomacy, Grandpa Joe's doggedness, Kevin's advocacy, Hank's compromise. Most of all, I see glimmers— brief resurrections—of John, whose disease stripped away so much, but left in clear relief his kindness and humanity.  Dr. Lidia Schapira: Hello, and welcome to JCO's Cancer Stories: The Art of Oncology, which features essays and personal reflections from authors exploring their experience in the field of oncology. I'm your host, Dr. Lydia Schapira, Associate Editor for Art of Oncology and a professor of medicine at Stanford University. Today we're joined by Dr. Matthew Farrell, a radiation oncology resident at UCLA. In this episode, we will be discussing his Art of Oncology article ‘First Cousin Once Removed'. At the time of this recording, our guest has no disclosures.   Matt, welcome to our podcast, and thank you for joining us. Dr. Matthew Farrell: Thank you so much for having me. Great to be here. Dr. Lidia Schapira: It's our pleasure. I'd like to start this conversation just asking a little bit about your reading preferences. Are there any books that are on your figurative night table right now that you'd like to recommend to our listeners?  Dr. Matthew Farrell: Yeah, a lot of times that night table is very figurative in that I am listening to audiobooks. Living in LA, I spend a lot of time in the car, so I listen to a lot of books. But I do like to physically read certain books, and one of those recently was George Saunders' new collection of short stories, Liberation Day. He is a wonderfully creative, funny, warm-hearted writer of short stories, which is one of my favorite forms. It's what I've written the most and what I studied the most back when I was in school, taking classes, undergraduate and graduate in creative writing.  Dr. Lidia Schapira: Tell us a little bit about your passion for writing and how you have integrated that into your professional life now as a medical oncologist?  Dr. Matthew Farrell: Yeah, I studied writing and was interested in writing before I transitioned to medicine. So, I minored in creative writing in college, and then I went to graduate school to get a Master of Fine Arts in creative writing and fiction writing. And it was partially that process that eventually led me into medicine. I realized that a lot of what I was writing about actually had to do with medicine. And as I was rereading some of my own work, I was drawn to stories of illness and family and recovery and processing grief, and I decided that those stories were really compelling to me and decided to transition to medicine. It was also helpful that my wife - girlfriend at the time - was applying to med school, so I had that idea in my head, and she was inspiring to me. So, I transitioned to medicine.I love to keep writing. I still love writing, and a lot of what drew me into oncology specifically is the brilliant, captivating, moving stories of interacting with people. And so it's one of my outlets and things I do for fun, as well as a way of helping me process what I see.  Dr. Lidia Schapira: Before we talk about this story, let's talk a little bit about your ideas of the language that we use, because I know you've written about that as well. So, as a writer and as a person who loves to reflect and find story, tell us a little bit about how you negotiate the words you use and the language you hear your colleagues and your peers using with patients.  Dr. Matthew Farrell: Coming from a writing background, where in workshop, we would go through our own stories, my writing professors would go through each word with a fine-toothed comb and sometimes in very elaborately, critical ways would say that this is a terrible word, this destroys the whole sentence, the whole story. And it just had me paying attention to the written language as well as the spoken language. And one of my creative writing mentors, my thesis advisor Ahud, he had leukemia and eventually died of leukemia, and he talked a lot about the experience of having cancer and the way that cancer is often talked about in this kind of heroic way in which the treatments are weapons and cancer is waged on a battlefield and people with cancer are heroes of that and how that can be very empowering in certain circumstances and also very draining in others. Dr. Lidia Schapira: Those are such fine points, and it's obvious that you're very careful about the language that you use in your writing. So, let's talk a little bit about this piece that we've just published in JCO that is a little different than most of the pieces because it describes scenes. Tell us about how you put these scenes together, what it meant to you, and what the overarching message is for your readers.  Dr. Matthew Farrell: Yeah, I think I'm used to writing scenes. I'm used to writing both fiction and nonfiction stories like this, and when I was approaching this, I just wanted to try to capture the experiences as I had understood them. And I also talked a lot with my family about them to try to remember what it was like and how our thoughts have changed on it over time. And so I tried to capture who John was and my memories of him as best as I could. I think that the best way to get across people's personalities, their vibrancy, is by writing scenes about them, because I can never describe someone as well as they can illustrate themselves through their own actions and dialogue. Dr. Lidia Schapira: So John was this figure that you had admired as a child and was so interesting, and then you bring us to a very debilitated John and some scenes in his apartment. Tell us a little bit about the time, the context, and the illness.  Dr. Matthew Farrell: Sure. This was the mid-1990s, and there were a lot of changes going on in the care of HIV and AIDS, a lot of rapid changes in our understanding of the illness as well as the treatments available for it. And it was really hard and devastating that John was able to see a lot of promising treatments on the horizon, but they weren't readily available to him when he needed them. And so it's tragic to think about, if all of this had happened just a year later with the rollout of HAART, or Highly Active Antiretroviral Therapy, his story might have been completely different, and he could easily still be here today, but he just missed it. And so that was very hard to see him go from being just about as vibrant and healthy and active a person as can be imagined, someone who I just envied and admired in terms of his physical ability; for him, if he could go from where he was to where he ended up, it was just completely devastating. Dr. Lidia Schapira: And then there was the stigma of the disease and the scene that you so beautifully share in your piece about different family members coming in to talk with him and say their goodbyes. And I think it was your grandfather who just couldn't let go of the ‘you must fight, you're going to get well' narrative. And I think your father, who is a psychologist, was sort of saying, "Hey, wait, we're having the wrong conversation here. This isn't what we agreed to." Can you tell us a little bit about what that felt like to you, observing it, perhaps your younger self and how you've thought about that now as a professional who's probably having these difficult conversations with patients?  Dr. Lidia Schapira: This was my first experience with these sorts of conversations, and I think about them a lot now, is I do have these talks with people, and I just can picture my Grandpa Joe charging in there and saying, "You can fight this," completely out of tune with what the goal was. And he and my father are similar in some ways, but very different in others. My father is very relaxed, easy-going. He could come to a cordial agreement with a grizzly bear, and my grandfather was that grizzly bear in some respects, and he was stubborn and not always the best listener. But what was striking about it to me is that I know that my grandfather's actions in that moment, even though they weren't in line with what we were trying to do or what my father and the hospice folks were trying to have us do, they still came out of love and out of devotion to John. Grandpa Joe, how he expressed his love for his family was through fighting for them, and so he was doing that for John in the only way that he knew.  And so when I am involved in conversations toward the end of life with goals of care now and I see situations in which people don't always reach the same page or come to the same understanding, I'm reminded of the fact that that can be surprising and frustrating, but it's okay because people process grief in their own ways and express love in their own ways.  Dr. Lidia Schapira: I can just imagine you're thinking about that when you're in a room and you're sort of casting people, "Oh, this is a Grandpa Joe. He means well, he loves a lot, but we just need to help him to understand what's happening." And there's another character in your story that I want you to talk a little bit about, and that's Kevin, the loving partner and caregiver, who's first sort of marginalized by the large group descending upon them and claiming John. And then there's a scene where there's peace between all factions. Tell us a little bit about how that felt to you, witnessing it as a child and how you thought about it in the years that came later.  Dr. Matthew Farrell: Yeah, I was still very young at the time, but these scenes completely seared themselves into my memory. And the piece that ended up coming out of this scene was due to Kevin and Kevin alone and his love for John, which he communicated so well, as well as the knowledge he had of John's wishes that other people didn't have. That is what allowed people to come together and to begin healing. And it has reminded me that it is never too early to share your wishes with people you love who can then be advocates for you when you can no longer advocate for yourself. I tend to think about it this way: when you communicate your wishes to other people, you are allowing yourself to get the type of care you want and not get the type of care that you don't want. But you're also giving a gift to your loved ones because by Kevin communicating what John wanted to our family, to John's father, it gave everyone the confidence that they knew that they were giving John what he wanted. And that provided a lot of comfort. So if you share that with someone and then they have certainty that they're helping you achieve what you would want. And that's the gift that Kevin gave to our family that none of us will ever forget.  Dr. Lidia Schapira: I think the use of the word ‘gift' is wonderful, totally appreciated. And I understand you're very deliberate with your choice of words, so I appreciate that. I think that we don't quite know how to value sometimes some of the gifts that our patients give us in the exam room, at the bedside, in terms of how they help us, help them by being clear, by expressing their gratitude often. And you bring that out so beautifully.  So as a gifted and trained writer who's now embarking on a career in radiation oncology, how are you going to continue to combine these talents? Are you writing a play or what are your plans?  Dr. Matthew Farrell: I still just write a lot in whatever comes to me. And I do write a lot about medicine and also a lot not about medicine. And it's fun for me. I did study writing formally, but I still have tons to learn all the time and I'm still learning from other people. And I try to be as open as I can to feedback in my own writing. I am, among other things, trying to write a screenplay, like many people in LA. I also worked briefly in the film industry for a summer at a film management company, and there was this joke about how everyone in LA is writing a screenplay, but almost no one has written a screenplay. And so I'm unfortunately still in the former category, but working on it. Dr. Lidia Schapira: Is there something you've learned working in the film industry that you want to share with your colleagues working in oncology that could help us be better doctors?  Dr. Matthew Farrell: One is just, I think, movies, shows, writing, a lot of it is focused on people and humanity and the human condition. And I find those stories very moving. And those sorts of stories are also very present and central in medicine. I think that obviously, by getting to know people, you can help them achieve what they want. I know that, again, this whole story was my first encounter with the limitations of medicine and when there aren't very many treatment options available to help people therapeutically. But still, there were many good outcomes for us to work toward in this situation, and in oncology, too. Whether that's helping to provide understanding, helping people come together, helping provide comfort. I know hospice and palliative care was incredibly helpful to John, and that's one of the things that I like about radiation oncology, among many other things, is its role in palliative care, and palliation in terms of reducing pain, reducing bleeding, reducing suffering, enabling functional gain and quality of life. And yeah, I think that the stories that I encountered in movies, which I got a great appreciation for, among other things from John, and the stories that I read about in my study and writing, I still am learning and experiencing those stories in medicine. And it's been each kind of phase that I was in have been incredibly moving to me and have helped me grow as a person.  Dr. Lidia Schapira: So before we end, I have to ask you this question. Do you have a favorite illness memoir or story that has been published or has been used to inform a play?  Dr. Matthew Farrell: One of the writers that I've studied the most who wrote about medicine as well as illness was Anton Chekhov. I took a whole course on him when I was in graduate school and he was a physician, one of the great physician writers of all time. And he wrote about, in contrast to what a lot of other writers were writing about at the time, he wrote about doctors, people, peasants, everyday humanity in really moving ways. And he just has so many stories about illness and pain and loss that are all worth reading.  Dr. Lidia Schapira: Well, thank you. It's been a lovely conversation. We enjoyed reading your story and learning about the family. Thank you for sharing that with us.  Until next time, thank you for listening to JCO's Cancer Stories: The Art of Oncology. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all of the ASCO's Shows at asco.org/podcasts.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  Like, share and subscribe so you never miss an episode and leave a rating or review. Guest Bio:   Dr. Matthew Farrell is a radiation oncology resident at UCLA.

In this episode, we review the high-yield topic of Kaposi Sarcoma from the Oncology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets

Dr. Esther Freeman started learning about outbreaks around the kitchen table! As a trained epidemiologist and dermatologist, she has become an "inadvertent" outbreak dermatologist during the COVID-19 pandemic. She shares her experience with emotions across cultures, the value of hard work in dermatology (and life), and a story about the refrigerator. Dr. Esther Freeman, MD PhD DTM&H is Associate Professor of Dermatology at Harvard Medical School. She is a board-certified dermatologist. She attended Dartmouth College and the London School of Hygiene and Tropical Medicine before receiving her MD from Harvard Medical School, where she also did her dermatology residency. She received her Diploma in Tropical Medicine and Hygiene from the Gorgas Memorial Institute in Peru. Her research looks at HIV-associated malignancies like Kaposi sarcoma and consults for the World Health Organization. 

Vaccine development is a tremendous scientific breakthrough benefitting countless human lives. In Part 1 of this ASCO Oncology, Etc. Education Podcast episode, you will hear from the pioneering co-developer of the HPV vaccine Dr. Doug Lowy who serves as Principal Deputy Director of the National Cancer Institute , He speaks about how he got into the cancer field through the influence of his parents (4:49), the path that led him to focus on HPV (8:04), and his collaborative professional partnership with fellow HPV vaccine developer Dr. John Schiller (9:31). He also discusses his ongoing trial of one-dose administration, which promises to boost HPV vaccine uptake and reduce the burden of cervical cancer globally. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org. TRANSCRIPT Pat Loehrer: Hi, I'm Pat Loehrer. I'm Director of the Center of Global Oncology and Health Equity at Indiana University. Dave Johnson: I'm Dave Johnson. I'm a Professor of Medicine at UT Southwestern Medical Center in Dallas, Texas. Pat Loehrer: And this is Oncology, Etc. Dave, what have you been reading lately? Dave Johnson: Well, you and I have talked about a couple of books, but I thought in light of our guest today, I would mention a book I actually read probably nearly 60 years ago called The Microbe Hunters by Paul de Kruif - very interesting book, written, if memory serves me correctly, in the '30s, about many of the early bacteriologists and physicians who were interested in microbes; Pasteur, for example, and others. And I don't remember all the details, but it certainly was one that was influential for my choice of Medicine as a career, much like Arrowsmith. It was a really impactful book. I doubt many of our listeners today would've read that book, but if one is interested in the history of Medicine, it's a really interesting book to read. Pat Loehrer: You said 60 years ago. Okay, when I was reading books back then, it was about Dick and Jane. Dave Johnson: It's my understanding that you're not past Dick and Jane yet. Pat Loehrer: Good, good point. Good point. Well, it's such an incredible honor today, we have Dr. Doug Lowy as our interviewee today. Doug is the Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory and Cellular Oncology Program at the Center for Cancer Research. He has served as Acting Director more than any other person - he served as Acting Director between April of 2015 and October of 2017, between April of 2019 and October of 2019, and most recently, he served as an Acting Director until Monday of this week, October 3rd. I had a chance of seeing Doug, I think, about a year ago, a week after he took over, and this is great to have that bookend here. He has had this title of Principal Deputy Director since July of 2010 and he leads many of the NCI's key scientific initiatives. He graduated from Amherst College, I think in Art History, I may be wrong on that, received his medical degree from New York University School of Medicine, trained in Internal Medicine at Stanford, and did a Dermatology Residency at Yale. His focus has been on papillomavirus and the regulation of normal and neoplastic growth. The papillomavirus is in close collaboration with Dr. John Schiller with whom he's co-authored 150 papers over the last 25 years. In the 1980s, he studied the genetic organization of papillomaviruses and identified oncogenes that were encoded by the virus, and he's been integrally involved and instrumental in the development of the papillomavirus vaccine. His laboratory did work with the RAS gene family and other suppressor genes, and as you can guess, he's just one heck of a smart guy. For his body of work and together with Dr. Schiller, they received the Federal Employee of the Year Award in 2007 and the Partnership for Public Service Award, the Dorothy P. Landon American Association for Cancer Research Prize for Translational Research, the Albert B. Sabin Gold Medal in 2011. In 2007, he got the Medal of Honor for basic research from the American Cancer Society, and President Obama awarded him the National Medal of Technology and Innovation in 2014. And in 2017, he received the Lasker-DeBakey Clinical Medical Research Award, which is considered one of the most prestigious honors in biomedical research. He is listed in the Institute of Scientific Information as one of the most highly-cited authors in Microbiology, and obviously, he's a member of the National Academy of Science and the National Academy of Medicine. Although these are notable honors, I'm told that none of them match the opportunity to speak with Dave and I today, and we really thank you so much, Dr. Lowy, for joining us. Thank you. Dr. Doug Lowy: Pat, I am speechless. Pat Loehrer: I so wish that Dave Johnson was, but could you tell us a little bit about your upbringing and your early life? Dr. Doug Lowy: Sure. I grew up in The Bronx, in New York City. I'm the younger of two boys. My brother is two and a half years older than I am. Both of my parents were general practitioners. My parents were both Americans, but my father had a classic sophomore slump when he was an undergraduate and was unable to get into a medical school in the United States. And so, he actually went to medical school in Austria, in the University of Vienna, and needed to learn German in order to go to medical school. But my parents were both very successful private practitioners. They had separate practices but practiced in the same office, and I learned about medicine, in large part, through them. They would go to lectures, and from the time I was probably nine or 10 years old, they would be telling me about cancer, and I became interested in that area. And then, when I was 16, my mother developed a deep melanoma on her leg, and so, cancer literally came home. And luckily, she had very good surgical treatment and lived for almost another 40 years - she lived until she was 80 and actually died of metastatic stomach cancer. But I got involved in thinking about cancer really through my parents. They talked with me about the role of tobacco in the development of lung cancer, and I heard about the Hammond and Horn report from the mid-1950s when it came out. Pat Loehrer: That was when Dave was reading the Microbe Hunters. Dr. Doug Lowy: I was reading it at about the same time. I must say that, although I found it very interesting, it didn't really speak to me, and now that's what I need to go and do. Although, in retrospect, that's what I've ended up going and doing. Pat Loehrer: Was it because of your mother that you had an interest in dermatology? How did you swing into there? Because we think of you mostly as a translational researcher. Dr. Doug Lowy: The dermatology was really when I was at NYU. I worked in the laboratory of Jan Vilcek, who had recently come from Czechoslovakia to NYU, and in his lab was Alvin Friedman-Kien, who was a dermatologist. And Alvin subsequently was among the first people to identify the AIDS epidemic through the Kaposi sarcoma. But Alvin talked with me about dermatology, and potentially, this might be an interesting field for me to go into. And then, when I went to Stanford, I did Internal Medicine for internship and a year of Medicine, and I did a rotation in Dermatology. And I was very impressed that the people who smiled the most were the dermatologists. And they had time also to think about what was going on with patients. And since I was at Stanford, it was a tertiary care facility and so we were taking care of people who were terribly sick, largely people with lymphoma and other types of cancer. And I thought that I might be better suited to taking care of people who were less sick than that. Dave Johnson: Is that where your interest in Papillomavirus started? Dr. Doug Lowy: Well, that was indirect. I first went into dermatology and then said, "Well, I want to be doing research. What can I do in research that might be connected both with dermatology as well as with cancer?" And the closest that I was able to come was Papillomaviruses. And when I started working on them, they were not yet clearly associated with cancer the way they are today. It was known that they were associated with an uncommon condition called Epidermodysplasia Verruciformis or EV and this is a condition where people have widespread HPV infection. And on sun-exposed areas, a subset of them develop skin cancer, but it's distinctly uncommon. The real interest, if you will, came from the identification of HPV infection and cervical cancer, which is one of the more common cancers, especially on a worldwide basis. And that was really the link with cancer. Pat Loehrer: You had an incredibly long-term collaboration with John Schiller, and as I mentioned, you published more than Dave and I have written letters to our wives with this man. Tell us a little bit about that relationship, that friendship, and that professional partnership. Dr. Doug Lowy: John, actually, he was at the University of Washington in Seattle doing his PhD, and it was so long ago that he sent me a letter, and I had been doing research on retroviruses. He sent me a proposal that he was doing his PhD in bacterial genetics, but he wanted to learn about mammalian viruses and so was writing to me about doing work with retroviruses. I wrote back to him and said, "That's very interesting, but I had just started working on papillomaviruses." And I thought the room for development and learning more was even greater there than with mouse retroviruses, which is what I was working on and what he was proposing to do some post-doctoral research on. Of course, he had never heard of papillomaviruses, so he had to look them up. But he developed a project with papillomaviruses and was able to get an NIH award to come as a postdoctoral fellow to work in my lab, and he actually did the research that he proposed, and it led to our improved understanding of the genetic organization of papillomaviruses. But then, it was clear that John and I got along very well, and it looked like both of us might be able to work together. So, he ended up getting tenure after he had been at NIH for about 10 years. And it's just been an amazing collaboration for me because John knows a lot of things that I don't know, and he thinks that I know some things that he doesn't know. And working together has been terrific, really, because when one of us doesn't want to do anything about something, the other one tends to step in. And so, it's been an amazing partnership that we have had for this time. Dave Johnson: This is really important. One of the reasons we agreed to do this podcast is to provide insight to up-and-coming faculty and fellows about mentoring and partnerships. What is the most important aspect of your partnership with Dr. Schiller? Dr. Doug Lowy: I think treating him as an equal colleague from day one, that probably is important. And then, since I was senior and he was junior, trying to make sure that he got credit when discoveries were made because the default, otherwise, was going to be that it was Doug Lowy who was doing things, whereas it was very clear that John was a key part of this collaboration. Dave Johnson: Now that your relationship is a long-lasting and mature one, how do you make those decisions now? Dr. Doug Lowy: Well, we've just worked together for a long time, and we enjoy talking, and actually, over the last few years, we are collaborating less rather than more. We're still very close colleagues, and we're in the same lab. But since I've been Deputy Director, especially during the last seven and a half years, I've been Acting Director for about three and a half out of the last seven and a half years, and there just isn't enough time to devote to the lab. And it would've been inappropriate for me to have been considered a co-principal investigator with John, who has gone off and done a lot of amazing research, more or less independent of me. Like everything else in this world, it develops, it continues to evolve, but we still are very close colleagues. As Pat was mentioning, this is my first week in several months not being Acting Director, and yesterday, John and I simply reveled in the opportunity to talk informally for 30 minutes without having to look at my watch because I needed to go someplace else. Dave Johnson: I'm glad you've reviewed that. I think a lot of junior faculty and fellows think that being in a leadership position is a cush job, and I'd tell them that it defies the laws of Physics because all poop flows uphill in this setting, and you have to deal with it. Pat Loehrer: I do want to spend some time talking about the NCI and your role there, but talk a little bit about how you have seen and where you envision that vaccines, particularly, HPV and maybe hepatitis vaccine - where you see it's been, and where it's going, and the impact that this potentially has on cancer worldwide? Dr. Doug Lowy: Well, one of the areas that John and I are continuing to work on closely is more research on the HPV vaccines. We noticed, quite a number of years ago, that the HPV vaccine performance was quite different from that of other so-called subunit vaccines. So, this is not an attenuated live vaccine, but instead is a subunit - it's just made up of one protein of the papillomavirus, the protein that gives rise to the outer shell of the virus. And what we noticed in a clinical trial that we were doing with colleagues in the intramural program, but who are medical epidemiologists - they are the leaders of the research, and what was happening was that although everyone was supposed to get three doses, there were some young women who were getting either two doses or one dose, in the trial, and this is in Costa Rica, where historically, cervical cancer has been the number one cancer of women. And it turned out that there was no difference in level of protection whether the women got one dose, two doses, or three doses. And even more surprising was that the antibody levels over the first few years were remarkably stable. And this led John and me to wonder whether it might be possible to get away with just a single vaccine dose. So, a lot of the research that we have been doing with our colleagues over the last few years is to develop stronger evidence that one dose of the vaccine would be sufficient to confer strong protection that's long-lasting. We've now carried out the studies in Costa Rica, with the initial trial to more than 10 years, and the antibody levels continue to be very stable, and the protection does not seem to have waned. Because this was not a pre-specified outcome, it's not enough to change standard of care. So, we and our colleagues are conducting a non-inferiority efficacy trial that is comparing two doses versus one dose of two different FDA-approved vaccines. One, GARDASIL 9, which is the HPV vaccine that's available for sale in the United States. But also Cervarix, which is made by GlaxoSmithKline, it's approved by the FDA, but it's no longer sold in the United States. And we anticipate that the results will read out in another couple of years. And if the results show that one dose and two doses are pretty comparable, we're expecting that this will lead to a worldwide change in recommendations for the HPV vaccine. So, whether you are in a high-income country or a low or middle-income country, that one dose is what will end up being recommended. Pat Loehrer: They could almost completely eradicate this disease, the most common cancer around the world. It's huge. Dr. Doug Lowy: So, Pat, the problem is that although the vaccine was approved 15 years ago, only about 10% of eligible young women in low and middle-income countries have actually been vaccinated up to now. And we think that the logistics and the cost of one dose could really be transformative, especially for those young women. It also would save the United States a great deal of money because needing only one dose would be far less expensive, and the government actually pays for about half of the HPV vaccine that is delivered to teenagers through the Vaccines for Children program.   Dave Johnson: Well, this concludes part one of our interview with Dr. Doug Lowy, Principal Deputy Director of the National Cancer Institute and Chief of the Intramural Laboratory of Cellular Oncology in the Center for Cancer Research. In the second part of this episode, Dr. Lowy will give his insight to vaccine hesitancy in the COVID era and the evolution of accomplishments over the past 50 years working at the National Cancer Institute. We want to thank all of our listeners for tuning in to Oncology, Etc. an ASCO Educational podcast, where we will talk about just about anything and everything. So, if you have an idea for a topic or a guest you would like for us to interview on the show, please email us at: education@asco.org.   Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click, Subscribe. Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center, at: education.asco.org. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy, should not be construed as an ASCO endorsement.    

Episode 120: Immune Reconstitution Inflammatory Syndrome (IRIS) Abeda Faharti and Dr. Schlaerth present the definition, diagnosis, and treatment of IRIS. Moderated by Dr. Arreaza. Written by Abeda Farhati, MS4, Ross University School of Medicine. Editing and comments by Katherine Schlaerth, MD, and Hector Arreaza, MD.You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Definition.Have you heard of IRIS? No, not the color portion of our eyes. IRIS is short for Immune Reconstitution Inflammatory Syndrome. This condition occurs in immunocompromised patients with HIV/AIDS due to an overactive inflammatory response. In most cases, it occurs after initiating antiretroviral therapy (ART). To understand IRIS in HIV patients, we must first understand HIV.HIV.The Human Immunodeficiency Virus (HIV) infection was first reported in 1981. The virus attacks the immune system, destroying white blood cells called CD4+ T lymphocytes, which are part of our body's defense mechanism. These cells are also known as "helper T cells" and are responsible for destroying viruses, bacteria, and other germs that make us sick.When your CD4+ count is low, you are more likely to get serious infections from viruses, bacteria, and fungi, which usually do not cause problems in otherwise healthy individuals. These infections are called Opportunistic infections, and they can be deadly. To restore CD4+ T lymphocytes, HIV patients are started on ART to normalize their immune response to pathogens. As a result of these treatments, HIV patients' lives have been significantly improved and prolonged. [Comment by Dr. Arreaza: It is paradoxical, but some HIV patients are among the healthiest patients I have seen.]Despite this, no treatment is guaranteed to be without side effects. Increases in CD4+ T lymphocytes trigger the immune system to respond to any persisting antigen, regardless of whether it is fragments or intact organisms. As a result, a hyperinflammatory response may occur.Diagnosis.There are no established criteria for diagnosing IRIS. It is generally accepted that IRIS requires the worsening of an existing infection or an unrecognized, preexisting infection in the context of improved immune function. For a diagnosis to be made, most, if not all of the following features must be present:The presence of a low CD4 count (less than 100 cells) before initiating treatment with ART (Except IRIS secondary to preexisting TB infection can occur with CD4 counts >200 cells).The presence of an inflammatory condition, especially after ART is initiated.The absence of drug-resistant infection, bacterial superinfection, drug allergy, or other adverse drug reactions.The absence of patient noncompliance or reduced drug levels due to drug-drug interactions or malabsorption.Clinical Manifestations.IRIS can be presented in patients in 2 ways:Patient's with a preexisting infectious disease that has NOT been treated, getting paradoxically worse after initiating treatment with ART ---this is known as “unmasking IRIS” ORPatient's with a preexisting infectious disease that has been previously diagnosed and treated but regained capacity after treatment with ART, causing it to mount an inflammatory response – this is known as “paradoxical IRIS.”In summary: Unmasking IRIS and paradoxical IRIS.Patients with IRIS have clinical features that vary widely. The presentations are strongly dependent on the type of preexisting opportunistic infection. For example, about 75% of patients with a mycobacterial or cryptococcal-related infection will develop a fever. In contrast, fever is rarely seen in cytomegalovirus (CMV) infections.Risk & Prevention.Researchers have found that lower CD4 cell counts or high HIV RNA levels at the time of anti-retroviral treatment initiation increase the risk of developing IRIS. One way to prevent IRIS development is to treat opportunistic infections prior to starting ART. Although this reduces the risk of IRIS development, it does not guarantee it.Treatment.In “unmasking IRIS,” patients can be treated with antibiotics, antivirals, or antifungals against the underlying infectious organism. In severe cases, steroids can also be used to suppress inflammation until the infection has been eradicated. Unfortunately, there is no treatment for paradoxical IRIS. Most patients who experience “paradoxical IRIS” reactions will get better spontaneously without additional therapy.Incidence of IRIS.The overall incidence of IRIS is unknown; however, studies have shown that anywhere from 25 to 30% of HIV patients who start antiretroviral treatment develop IRIS in the first six months. You may ask, which preexisting infections can lead to patients developing IRIS?Pathogens associated with IRIS.Different pathogens have been associated with the development of IRIS. The leading pathogens include:Mycobacterium tuberculosisMycobacterium avium complexCytomegalovirusCryptococcus neoformansPneumocystis jiroveciiHerpes simplex virusHepatitis B virusHuman herpes virus 8 (associated with Kaposi sarcoma)Non-HIV etiologies.IRIS can also be seen in other immunocompromised conditions, such as:Solid organ transplant recipients Postpartum period – 3 to 6 weeks after giving birthNeutropenic patients – with an absolute neutrophil count of less than 500Patients on Tumor Necrosis Factor Antagonists (TNF antagonists)- are used to treat chronic conditions such as ulcerative colitis, Crohn's disease, or sarcoidosis.In summary, Immune Reconstitution Inflammatory Syndrome (IRIS) is a hyper-inflammatory state seen after initiating ART in HIV patients whose improved immune system responds to previously acquired opportunistic infection, whether treated or not.The treatment is directed to the unmasked specific opportunistic infection or support therapy if no active infection is found.____________________________Conclusion: Now we conclude episode number 121, “Immune Reconstitution Inflammatory Syndrome (IRIS).” This syndrome presents in about 30% of HIV patients when they start ART. A stronger immune system means a stronger immune reaction. So, keep in mind this diagnosis when your HIV patients get sicker when they are supposed to get better after starting ART. This week we thank Hector Arreaza, Abeda Farhati, and Katherine Schlaerth. Audio edition by Adrianne Silva.Even without trying, every night you go to bed a little wiser. Thanks for listening to Rio Bravo qWeek Podcast. We want to hear from you, send us an email at RioBravoqWeek@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. See you next week! _____________________Links:“CD4 Lymphocyte Count: MedlinePlus Medical Test.” Medlineplus.gov, accessed on November 4, 2022.https://medlineplus.gov/lab-tests/cd4-lymphocyte-count/#:~:text=A%20CD4%20count%20is%20mostly,have%20trouble%20fighting%20off%20infections.Sun HY, Singh N. Immune reconstitution inflammatory syndrome in non-HIV immunocompromised patients. Curr Opin Infect Dis. 2009 Aug;22(4):394-402. doi: 10.1097/QCO.0b013e32832d7aff. PMID: 19483618. https://pubmed.ncbi.nlm.nih.gov/19483618/Thapa, Sushma, and Utsav Shrestha. “Immune Reconstitution Inflammatory Syndrome.” PubMed, StatPearls Publishing, 2022, www.ncbi.nlm.nih.gov/books/NBK567803/.Wolfe, Cameron. Immune reconstitution inflammatory syndrome, UpToDate. ww.uptodate.com, https://www.uptodate.com/contents/immune-reconstitution-inflammatory-syndrome. Accessed November 14, 2022.Royalty-free music used for this episode: “Keeping Watch,” New Age Landscapes. Downloaded on October 13, 2022, from https://www.videvo.net/royalty-free-music-albums/new-age-landscapes/. 

Videos : Niall Ferguson – Woke Totalitarianism (0:19 to 18:14) Heather Mac Donald On How The Delusion of Diversity Destroys Our Common Humanity (11:14) Elon Musk: “Klaus Schwab Is LYING!!!” (9:45) Lycopene, lutein supplements show skin protection from within against UV radiation Leibniz Research Institute for Environmental Medicine (Germany), November 10, 2022 The study's findings, published in the British Journal of Dermatology , indicated that oral supplementation with the carotenoids changed the expression of genes that are indicators of oxidative stress, photo-dermatoses and photo-aging. “To the best of our knowledge we show here for the 1st time that (i) tomato nutrient complex as well as lutein do not only protect healthy human skin against UVB/A, but also against long wave UVA1 radiation, and (ii) that oral photo-protection of healthy human skin can be demonstrated at the level of HO-1, ICAM-1 and MMP-1 gene expression,” wrote researchers from IUF – Leibniz Research Institute for Environmental Medicine in Dusseldorf. Heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1) and matrix metalloproteinase-1 (MMP-1) are reported to be UVA1/UVB radiation-inducible genes. “On top of that, as part of the photo-aging process we have evidence of the effect of our ingredients on the levels of expression of genes involved in collagen degradation, suggesting a link not only to skin health but also to skin appearance. This study suggests an effect of natural antioxidants on overall skin wellness, which is relevant for men and women in all age groups.” The new study included 65 healthy volunteers aged between 18 and 60. The participants were randomly assigned to randomly consume 20 mg per day of the tomato nutrient complex or placebo for 12 weeks, or 20 mg per day of lutein or placebo for 12 weeks. A two-week washout period separated the placebo and active intervention periods. At the beginning and at the end of each phase the skin was irradiated.Results of the placebo-controlled, double blinded, randomized cross-over study indicated that the tomato nutrient complex (TNC) totally inhibited the upregulation of HO-1, ICAM-1 and MMP1 mRNA by both UVA1 and UVA/B. On the other hand, lutein only completely inhibited gene expression if taken during the first 12 weeks (ie. prior to placebo), while a significantly smaller effect was observed if it was taken during the second 12 week phase (ie. after placebo), compared to TNC. (NEXT) Diallyl trisulfide in garlic induces apoptosis in primary effusion lymphoma Kyoto Pharmaceutical University (Japan), November 7, 2022 Reports from Kyoto Pharmaceutical University stated, “The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents.” Our news editors obtained a quote from the research, “Here, we found that DAT inhibited nuclear factor-kB (NF-kB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IkBa, and suppressed NF-kB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IkBa stabilization. The results indicated that DAT stabilized IkBa by inhibiting the phosphorylation of IkBa by the IkB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKb-phosphorylation through downregulation of TRAF6. It is known that activation of NF-kB is essential for survival of PEL cells. In fact, the NF-kB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells.” According to the news editors, the research concluded: “These findings provide evidence that DAT has antitumor activity against PEL cells in-vitro and in-vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL.” (NEXT) PTSD May Speed Up Cellular Aging Boston University, November 13, 2022 From birth to death, a lot may change, but our DNA—the long, double-helix molecule that contains all of a person's genetic code—stays the same. The instructions for reading that code can shift, however, as the chemical tags on and around a DNA sequence change throughout our lives, depending on our age, environment, and behavior. This outside influence on how our genes are read and expressed by cells is called epigenetics—and researchers studying it have discovered clues that may show why some veterans live longer than others. In a new study of military veterans published in Translational Psychiatry, researchers report findings that suggest former service personnel with PTSD are at greater risk of early death. “Our study found that PTSD and comorbid conditions, like substance misuse, are associated with a cellular marker of early death found in DNA methylation patterns,” says Erika Wolf, a professor of psychiatry at the Boston University School of Medicine and senior author of the study. The study included two samples of veterans that had representative levels of trauma and other psychiatric conditions, like substance use and personality disorders. One group included 434 veterans in their early 30s, who had served in post-9/11 conflicts; the other group included 647 middle-age veterans and their trauma-exposed spouses. Both groups were assessed for a range of psychological conditions, and had blood drawn to obtain genetic information and to test for levels of a variety of inflammatory molecules. The results indicate PTSD symptoms were a factor in faster cellular aging—.36 of a year faster. So, for every year that the cells of someone without PTSD age, the cells of someone with more severe PTSD symptoms age a year and a third. (NEXT) Higher sense of purpose in life may be linked to lower mortality risk Boston University, November 14, 2022 Growing research indicates that one's purpose—i.e., the extent to which someone perceives a sense of direction and goals in their life—may be linked to health-protective benefits such as better physical functioning and lower risks of cardiovascular disease or cognitive decline. Now, a new study led by a Boston University School of Public Health (BUSPH) researcher found that people with higher levels of purpose may have a lower risk of death from any cause, and that this association is applicable across race/ethnicity and gender. Published in the journal Preventive Medicine, the study results did suggest that this association is slightly stronger among women than it is among men, but there was no significant difference by race/ethnicity. “In another study I led, we found that the effect of purpose on lowering all-cause mortality may differ by socioeconomic status. In this study, we extended the prior evidence and found that the beneficial effect of purpose persisted regardless of gender and race/ethnicity.” For the study, the team assessed self-reported sense of purpose among more than 13,000 people, based on the “purpose in life” of the Ryff Psychological Well-being Scales, a widely used tool that measures different aspects of well-being and happiness. The researchers also examined mortality risk over an eight-year period beginning between 2006-2008. The results showed that people with the highest sense of purpose indicated the lowest risk of death (15.2 percent mortality risk), compared to people with the lowest sense of purpose (36.5 percent mortality risk). The team also gathered data on additional factors that can influence health, such socioeconomic status, other demographic characteristics, baseline physical health, and depression, and found that an increase in these factors was also associated with increases in a higher sense of purpose. (NEXT) Hibiscus compound shows anti-Alzheimer disease activity Pohang University of Science and Technology, November 16 2022. A report published in Alzheimer's Research & Therapy revealed that gossypetin, a flavonoid occurring in the calyx of the hibiscus flower, activates a process that reduces brain accumulation of amyloid beta, a protein that clumps to form toxic brain plaques in people with Alzheimer disease. Gossypetin has been reported to have antioxidant, antiatherosclerotic and anticancer effects. Earlier research had suggested a benefit for gossypetin, which is structurally similar to quercetin, against the aggregation of amyloid beta and tau proteins that occurs in Alzheimer disease. However, gossypetin's action in animal models of the disease had not been evaluated. Researchers at Pohang University of Science and Technology administered gossypetin or a control substance to mice that were bred to develop a condition similar to that of Alzheimer disease in humans. After 13 weeks of daily treatment, mice that received the flavonoid had less amyloid beta in the brain's hippocampus (an area involved in memory and learning) and cortex in comparison with the control mice. Gossypetin-treated animals also demonstrated better spatial learning and memory than untreated mice. Rather than affecting the production of amyloid beta, the research team found that gossypetin helped clear it by enhancing the scavenging ability of the brain's immune cells, which are known as microglia. Microglia normally consume amyloid beta but can become exhausted by continual exposure, which leads to a chronic damaging inflammatory reaction. (NEXT) Over a billion young people are potentially at risk of hearing loss from headphones, earbuds, loud music venues Mayo Clinic, November 15, 2022 More than 1 billion teens and young people are potentially at risk of hearing loss because of their use of headphones and earbuds and attendance at loud music venues, concludes a pooled data analysis of the available evidence, published in the open access journal BMJ Global Health. The World Health Organization (WHO) estimates that over 430 million people worldwide currently have disabling hearing loss. Young people are particularly vulnerable because of their use of personal listening devices (PLDs), such as smartphones, headphones and earbuds, and attendance at loud music venues, amid poor regulatory enforcement. Previously published research suggests that PLD users often choose volumes as high as 105 dB while average sound levels at entertainment venues range from 104 to 112 dB, exceeding permissible levels (80 dB for adults; 75 dB for children) even if for very short periods of time. A group of 33 studies, corresponding to data from 35 records and 19,046 participants, was included; 17 records focused on PLD use and 18 focused on loud entertainment venues. The pooled data analysis indicates that the prevalence of unsafe listening practices from PLD use and attendance at loud entertainment venues is common worldwide—24% and 48%, respectively, among teens and young people. Based on these figures, the researchers estimate that the global number of teens and young adults who could potentially be at risk of hearing loss as a result ranges from 0.67 to 1.35 billion.

In this thoroughly engaging episode, we hear from Dr.Steven Watiti who works for  Mildmay Uganda, a leading HIV and AIDS service organisation, about living and aging with HIV and AIDS. Steven shares his story of family life, courage, loss, survival, learning, and advocacy. He speaks about the importance of mental health support and social capital when living with a lifelong health condition and calls for others to respond.   Dr Steven Watiti Patient representative on Respond-Africa Partnership After studying Medicine at Makerere University, Kampala, Uganda, Dr. Watiti, was a medical officer, Rubaga Hospital, Kampala from 1985-1988. He practiced medicine privately from 1988-2004 at Entebbe Road clinic and JOY Medical Centre Ndeeba, Kampala. From 2004, he has been working at Mildmay Uganda, a leading HIV and AIDS service organisation. An HIV activist and ardent advocate for improved and sustainable health for all, Dr. Watiti believes with hindsight that he acquired HIV between 1985 and 1986 while working as a junior medical officer. In 2000, he began ARVs after contracting tuberculosis, cancer (Kaposi's sarcoma), and meningitis. In 2006, he started his weekly column on HIV in New Vision, Uganda's leading daily newspaper. His column appears Mondays under the heading: “Towards zero: with Doctor Watiti”. He has published two books on HIV: “HIV and AIDS: 100 Commonly Asked Questions” and “Conquering HIV and AIDS: My personal experience of living with HIV”. Dr Waititi works with the Respond Africa partnership as an expert patient ensuring that patient needs, views and voices are heard and considered and addressed when designing and implementing research projects.  Twitter: @WatitiStephen  https://inteafrica.org/ (https://inteafrica.org/)  Dr. Rhona Mijumbi-Deve Dr. Rhona Mijumbi-Deve is a senior lecturer of public policy at the Liverpool School of Tropical Medicine (LSTM) and heads the Policy Unit at the Malawi Liverpool Wellcome Clinical Research Programme in Blantyre, Malawi. Rhona trained as a medical doctor and later as a Clinical Epidemiologist and Biostatistician, and health policy analyst. She has spent the past decade doing health systems and policy research. Her special interest is in exploring the nexus of evidence, and policy and decision-making processes, especially in low- and middle-income countries. She especially is interested in understanding this in the contexts of emergencies, health security and health diplomacy. 

In this week's episode, we will be talking about the economic impact of non-communicable diseases or NCDs on east African communities. Guests include Dr. Steven Waititi, a Patient representative on Respond-Africa Partnership and author of “Conquering HIV and AIDS: My personal experience of living with HIV” and Josephine Birungi, a Senior Research Scientist based at Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) in Entebbe. They discuss:  Financial/economic barriers for patients and communities affected by NCDs  What having an NCD means for patient finances  How integrated care addresses these problems  Dr Josephine Birungi Senior Research Scientist, MRC +UVRI& LSHTM Uganda Research Unit  Dr Josephine Birungi is a Senior Research Scientist based at Medical Research Council/Uganda Virus Research Institute (MRC/UVRI) in Entebbe. She is currently working on a number of research project within the Respond Africa Partnership, as study lead in Uganda. Projects include  INTEAFRICA which is evaluating a novel approach of integrated clinical management of HIV-infection, diabetes, and hypertension in Tanzania and Uganda and INTECOMM which is evaluating community based integrated care for people living with HIV, Diabetes and Hypertension.  https://inteafrica.org/ (https://inteafrica.org/)  @josephinebirun1  Dr Steven Watiti Patient representative on Respond-Africa Partnership After studying Medicine at Makerere University, Kampala, Uganda, Dr. Watiti, was a medical officer, Rubaga Hospital, Kampala from 1985-1988. He practiced medicine privately from 1988-2004 at Entebbe Road clinic and JOY Medical Centre Ndeeba, Kampala. From 2004, he has been working at Mildmay Uganda, a leading HIV and AIDS service organisation. An HIV activist and ardent advocate for improved and sustainable health for all, Dr. Watiti believes with hindsight that he acquired HIV between 1985 and 1986 while working as a junior medical officer. In 2000, he began ARVs after contracting tuberculosis, cancer (Kaposi's sarcoma), and meningitis. In 2006, he started his weekly column on HIV in New Vision, Uganda's leading daily newspaper. His column appears Mondays under the heading: “Towards zero: with Doctor Watiti”. He has published two books on HIV: “HIV and AIDS: 100 Commonly Asked Questions” and “Conquering HIV and AIDS: My personal experience of living with HIV”. Dr Waititi works with the Respond Africa partnership as an expert patient ensuring that patient needs, views and voices are heard and considered and addressed when designing and implementing research projects.  https://inteafrica.org/ (https://inteafrica.org/)  @WatitiStephen 

This Episode is the eight of the first season. Ringmaster defends himself against the cocky Master of Ceremonies. Pax walks us through the complexities of Kaposi's Sarcoma We discuss the stigma associated with KS Master of Ceremonies is visited by The Twins of Terror Trick Rider greets the two as they leave the Bastion

Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Beware Invisible Mistakes, published by kuhanj on May 4, 2022 on The Effective Altruism Forum. Some kinds of mistakes are very visible/salient. Mistakes in execution are often salient. When you organize an event and very few people show up, it's pretty clear that you didn't do enough advertising, or that your advertising was ineffective, or the thing you were organizing an event around wasn't interesting enough to other people in the first place (or something else, gotta hedge :D). Mistakes that are publicly visible (or at least visible to some others) are also (way) more salient. I have spread myself too thin, and overpromised and underdelivered - and have let others down. Other people knowing the mistakes I've made makes them quite salient. Other kinds of mistakes are harder to notice, sometimes so much so that we don't even realize they're mistakes. These often relate to opportunity cost, which is the difference between the thing you did, and the best thing you could have done instead. When I waste a few (high energy/high-focus) hours, or sometimes a whole day (rip) on Youtube, the opportunity cost of what I could have done with that day is often not very salient. (This specifically is no longer an issue, thanks Cold Turkey!) It's really sad to think about how much more good I could have accomplished with all the time I spent watching tennis and Youtube, or how much more effective I'd be if I'd sufficiently invested in my productivity habits and mental/physical health at a younger age. Strategic mistakes are often not salient (h/t Nate Thomas). It might not be very clear that you're making a mistake if you're doing something really well, but are focusing on the wrong thing entirely - e.g. getting really good at performing surgeries for Kaposi's sarcoma instead of optimizing education about HIV/AIDS for high risk groups (see here for more). (Yes, this is also an example of opportunity cost). Doing things is hard. When you do things, you often subject yourself to lots of potential scrutiny. If you try and fail, your failure is salient, and often visible to (some subset of) the world. If you don't try at all, no one blames you for not trying. I'd love for us to be more cognizant of strategic mistakes/opportunity cost/other low-salience things, and hold ourselves to higher standards. Though this post is focused on mistakes and correcting them, we shouldreward each other for pushing ourselves (which can look like running experiments to find out how to optimize our productivity, determining how much and what kinds of work we can do sustainably, getting coaching, etc), and for actually trying, even if we fail. So how can we make these invisible mistakes more salient, and integrate these ideas into how we spend our time and make decisions? Internalizing the concept of opportunity cost and the extreme importance of time has made the cost of wasting my time much more salient to me. Estimating (with lots of uncertainty) how much good I can do per hour (e.g. in terms of lives saved, OpenPhil dollars spent, etc) has had a similar effect. Thomas Kwa's post Effectiveness is a Conjunction of Multipliers makes the importance of strategic mistakes quite clear. Brief summary: Not considering one 10x multiplier, even when I correctly identify five others, means only having 10% of the impact I could've had if I had considered it. Perhaps the most important examples of how thinking about strategy has been important for me have been: Reading, talking to people, and thinking a lot about cause prioritization, and Regularly asking myself “What might be 10 (or 1000) times more impactful than what I currently work on?”. Figure out ways to spend your time and resources more effectively. Figure out which kinds of work you can excel at (I recommend checking out this post for ideas). Figure out ...

In this episode from the series “Key Decisions in HIV Care,” Cristina Mussini, MD, and William R. Short, MD, MPH, AAHIVS, discuss important considerations for ART with opportunistic infections, including: When to start ART with pneumocystis pneumonia including discussion of the ACTG 5164 study of immediate vs delayed ART with opportunistic infectionsEACS, DHHS, and IAS-USA guideline recommendations for starting ART in the setting of most opportunistic infectionsConsiderations for the administration of ART to patients who are unable to swallow or critically ill and intubatedTreatment of Kaposi sarcoma and considerations for starting ART to avoid drug–drug interactions with Kaposi sarcoma treatmentConsiderations for starting ART with cytomegalovirus and the risk for IRIS from cytomegalovirusDiscussion of treatment of cytomegalovirus and overlapping toxicities between its treatment and ARTWhen to start ART with cryptococcal meningitis and the data to support delayed treatment initiation with this particular opportunistic infectionEACS, DHHS, and IAS-USA guideline recommendations for starting ART in the setting of cryptococcal meningitis specificallyTreatment of cryptococcal meningitis and managing drug–drug interactions between ART and antifungal therapyPresenters:Cristina Mussini, MDHead of Department of Infectious Diseases and Tropical MedicineFull Professor of Infectious DiseasesInfectious Diseases Clinics University HospitalUniversity of Modena and Reggio EmiliaReggio Emilia, Italy William R. Short, MD, MPH, AAHIVSAssociate Professor of MedicineDivision of Infectious DiseasesDepartment of MedicinePerelman School of Medicine at the University of PennsylvaniaPhiladelphia, Pennsylvania Content based on an online CME program supported by educational grants from Gilead Sciences, Inc.; Janssen Therapeutics, Division of Janssen Products, LP; and ViiV Healthcare.Follow along with the slides at:https://bit.ly/3uktrm1Link to full program:https://bit.ly/3q2DlGd

♦ Esiste una lista ufficiale di malattie legate direttamente al mondo omosessuale. Secondo la rivista Science News, una “rara forma di cancro e spesso rapidamente fatale”, chiamata sarcoma di Kaposi, è stata diagnosticata in decine di omosessuali. Alcuni di loro sono morti entro 24 mesi dalla diagnosi. Secondo l'articolo, analizzando le cose in comune fra le vittime, è stato riscontrato che avevano “frequenti incontri sessuali con molti partner diversi” e “molte di loro erano già state trattate per herpesvirus, citomegalovirus, virus dell'epatite B e infezioni parassitarie”, malattie comuni fra gli omosessuali. Secondo Medical World News, gli epidemiologi di San Francisco, California, e di altre grandi città americane hanno condotto studi approfonditi alla ricerca di indizi che spieghino perché la polmonite da Pneumocystis carinii – una pericolosa malattia, spesso letale, che è solitamente associata a una grave immunosoppressione – si è improvvisamente manifestata in giovani omosessuali sani. La rivista aggiunge che i medici “sospettano che il denominatore comune possa essere una pratica unicamente omosessuale o una malattia nascosta acquisita con il rapporto sessuale”. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/corgiov/message

En el video de hoy revisamos algunas de las enfermedades acompañantes más frecuentes del VIH, cosas como las infecciones oportunistas, la tuberculosis, las infecciones por herpes, algunos tipos de cáncer como sarcoma de Kaposi y linfomas, los problemas de neuropatía por VIH o por antirretrovirales, la demencia, los problemas de salud mental como adicciones o depresión, enfermedad cardiovascular y enfermedad renal.Checa el video aquÍ. https://youtu.be/_X3neasYe18Checa más información aquí:-Infección y cáncer oportunista: https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html-Otras comorbilidades: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/other-related-health-issues/other-health-issues-of-special-concern-for-people-living-with-hiv-Neuropatía por VIH: https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/peripheral_nerve/conditions/hiv_neuropathy.html-Enfermedad cardiovascular: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036211-Demencia: https://www.hopkinsmedicine.org/health/conditions-and-diseases/hiv-and-aids/hiv-and-dementia-Enfermedad renal: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-kidney-diseaseVisita nuestra tienda en línea para comprar nuestros libros y material educativo:https://bit.ly/3i6eAnGSi necesitas una consulta aquí nos puedes encontrar:http://bit.ly/3aUSt12Ayúdanos a encontrar los mejores hospitales para estudiar:https://bit.ly/36o82LXUnete al equipo de Mecenas en YouTube desde 1 dolar al mes: http://bit.ly/2O1AtsXSupport the show

En el video de hoy revisamos algunas de las enfermedades acompañantes más frecuentes del VIH, cosas como las infecciones oportunistas, la tuberculosis, las infecciones por herpes, algunos tipos de cáncer como sarcoma de Kaposi y linfomas, los problemas de neuropatía por VIH o por antirretrovirales, la demencia, los problemas de salud mental como adicciones o depresión, enfermedad cardiovascular y enfermedad renal.Checa más información aquí:-Infección y cáncer oportunista: https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html-Otras comorbilidades: https://www.hiv.gov/hiv-basics/staying-in-hiv-care/other-related-health-issues/other-health-issues-of-special-concern-for-people-living-with-hiv-Neuropatía por VIH: https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/peripheral_nerve/conditions/hiv_neuropathy.html-Enfermedad cardiovascular: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.036211-Demencia: https://www.hopkinsmedicine.org/health/conditions-and-diseases/hiv-and-aids/hiv-and-dementia-Enfermedad renal: https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-kidney-diseaseCheca el video aquí: https://youtu.be/_X3neasYe18Visita nuestra tienda en línea para comprar nuestros libros y material educativo:https://bit.ly/3i6eAnGSi necesitas una consulta aquí nos puedes encontrar:http://bit.ly/3aUSt12Ayúdanos a encontrar los mejores hospitales para estudiar:https://bit.ly/36o82LXUnete al equipo de Mecenas en YouTube desde 1 dolar al mes: http://bit.ly/2O1AtsXSupport the show (https://www.paypal.com/donate?hosted_button_id=2ENWQ7V289PBE)

En 2021 se cumplen 40 años desde el primer caso conocido de SIDA en España.DIA MUNDIAL DEL SIDAHan pasado 40 años desde el primer caso de SIDA en España.En octubre de 1981, un chico de 35 años ingresa en el hospital Vall D´hebron de Cataluña, con dolor de cabeza persistente, heridas de color púrpura en la piel y sarcoma de Kaposi. El joven manifiesta que a lo largo de unos seis meses, lleva observando desmejoría física, baja forma y pérdida de peso. Es hospitalizado con un diagnóstico de toxoplasmosis, una dolencia generada por consumir carne en mal estado. Pero el tratamiento no funciona. Sus dolores aumentan, parte de su cuerpo queda paralizado por un tumor cerebral. El deterioro sigue abriendose camino en su organismo, hasta la muerte. Años más tarde, con el VIH convertido en pandemia, se supo que aquel fue el primer caso de muerte por SIDA en España.Actualmente, casi 38 millones de personas en todo el mundo viven contagiadas por VIH. Afortunadamente, aumenta el acceso al tratamiento, que no cura, pero controla el virus. A pesar de eso, 680 mil personas murieron en 2020 por enfermedades relacionadas con el SIDA.Cada 1 de diciembre, se celebra el día mundial del SIDA, con objetivos como, la sensibilización hacia las personas contagiadas y desestigmatizarlas, hacer...

En 2021 se cumplen 40 años desde el primer caso conocido de SIDA en España.DIA MUNDIAL DEL SIDAHan pasado 40 años desde el primer caso de SIDA en España.En octubre de 1981, un chico de 35 años ingresa en el hospital Vall D'hebron de Cataluña, con dolor de cabeza persistente, heridas de color púrpura en la piel y sarcoma de Kaposi. El joven manifiesta que a lo largo de unos seis meses, lleva observando desmejoría física, baja forma y pérdida de peso. Es hospitalizado con un diagnóstico de toxoplasmosis, una dolencia generada por consumir carne en mal estado. Pero el tratamiento no funciona. Sus dolores aumentan, parte de su cuerpo queda paralizado por un tumor cerebral. El deterioro sigue abriendose camino en su organismo, hasta la muerte. Años más tarde, con el VIH convertido en pandemia, se supo que aquel fue el primer caso de muerte por SIDA en España.Actualmente, casi 38 millones de personas en todo el mundo viven contagiadas por VIH. Afortunadamente, aumenta el acceso al tratamiento, que no cura, pero controla el virus. A pesar de eso, 680 mil personas murieron en 2020 por enfermedades relacionadas con el SIDA.Cada 1 de diciembre, se celebra el día mundial del SIDA, con objetivos como, la sensibilización hacia las personas contagiadas y desestigmatizarlas, hacer...

 Updated September 2021 1 Presumptive Disability Benefits Whatis “Presumptive”Service Connection? VA presumesthat certain disabilities were caused bymilitary service. Thisis because of the unique circumstances of a specific Veteran's military service. If a presumed condition is diagnosed in a Veteran within a certain group, they can be awarded disability compensation. What are “Presumptive” Conditions? If you are diagnosed with a chronic disease within one year of active duty release, you should apply for disability compensation. Examples of chronic disease include: arthritis, diabetes or hypertension. Or, if you served continuously for atleast 90 days and are diagnosedwith amyotrophic lateralsclerosis (ALS) after discharge, you can establish service connection for the disease. Veteransin the following groups may qualify for “presumptive” disability benefits: • Former prisoners of war who: • Have a condition thatis atleast 10 percent disabling • Depending on length of imprisonment, specific conditions are presumed  Imprisoned for any length of time: • Psychosis • Any of the anxiety states • Dysthymic disorder(or depressive neurosis) • Organic residuals of frostbite • Post- traumatic osteoarthritis • Heart disease or hypertensive vascular disease • Stroke and the residual effects • Osteoporosis, when the Veteran has posttraumatic stress disorder Updated September 2021 2  Imprisoned for at least 30 days: • Beriberi (including beriberi heart disease) • Chronic dysentery • Helminthiasis • Malnutrition (including optic atrophy) • Pellagra • Other nutritional deficiencies • Irritable bowel syndrome • Peptic ulcer disease • Peripheral neuropathy • Cirrhosis of the liver • Avitaminosis • Osteoporosis • Vietnam Veterans who were: • Exposed to AgentOrange • Served in the Republic of Vietnamor on a vessel operating not more than 12 nauticalmiles seaward from the demarcation line of the waters of Vietnam and Cambodia between Jan. 9, 1962 andMay 7, 1975 • Specific presumed conditions are: • AL amyloidosis • B-cell leukemia • Chronic lymphocytic leukemia • Multiple myeloma • Type 2 diabetes • Hodgkin's disease • Ischemic heart disease (including but notlimited to, coronary artery disease and atherosclerotic cardiovascular disease) • Non-Hodgkin's lymphoma • Parkinson's disease • Parkinsonism • Prostate cancer • Respiratory cancers • Soft-tissue sarcoma (not including osteosarcoma, chondrosarcoma, Kaposi'ssarcoma or mesothelioma) • Bladder cancer • Hypothyroidism Updated September 2021 3  The following conditions, if they become greater than 10 percent debilitating within a year of exposure to an herbicide agent: • Acute and subacute peripheral neuropathy • Chloracne or other similar acneform disease • Porphyria cutanea tarda • Atomic Veterans exposed to ionizing radiationand who experienced one of the following: • Participated in atmospheric nuclear testing • Occupied or were prisoners of warinHiroshima orNagasaki • Served before Feb. 1, 1992, at a diffusion plantin Paducah, Kentucky, Portsmouth, Ohio orOak Ridge, Tennessee • Served before Jan. 1, 1974, at Amchitka Island, Alaska Specific presumed conditions are:  All forms of leukemia, except chronic lymphocytic leukemia  Cancer of the thyroid, breast, pharynx, esophagus, stomach, small intestine, pancreas, bile ducts, gall bladder, salivary gland, urinary tract, brain, bone, lung, colon or ovary  Bronchioloalveolar carcinoma  Multiple myeloma  Lymphomas, other than Hodgkin's disease  Primary liver cancer, except if there are indications of cirrhosis or hepatitis B • Gulf War Veterans who: • Served in the Southwest Asia Theater of Operations • Have a condition that is at least 10 percent disabling by Dec. 31, 2026 • Specific presumed conditions are:  Medically unexplained chronic multi-symptom illnesses that exist for six months or more, such as: • Chronic fatigue syndrome • Fibromyalgia • Irritable bowel syndrome  Any diagnosed or undiagnosed illness that warrants a presumption of service connection, as determined by the Secretary of Veterans Affairs Updated September 2021 4 • Signs or symptoms of an undiagnosed illness include: • Fatigue • Skin symptoms • Headaches • Muscle pain • Joint pain • Neurological or neuropsychologicalsymptoms • Symptoms involving the upper or lower respiratory system • Sleep disturbance • Gastrointestinalsymptoms • Cardiovascular symptoms • Weight loss • Menstrual disorders • Gulf WarVeterans who: • Served in the Southwest Asia Theater of Operations orinAfghanistan on or after September 19, 2001  Manifest one of the following infectious diseasesto a degree of 10 percent ormore within 1 year of separation: • Brucellosis • Campylobacterjejuni • Coxiella burnetii (Q fever) • Nontyphoid Salmonella • Shigella • West Nile virus • Malaria (or when accepted treatisesindicate the incubation period began during a qualifying period of service)  Manifestto a degree of 10 percent ormore at any time after separation: • Mycobacteriumtuberculosis • Visceral leishmaniasis • Gulf War Deployed Veterans who: • Served any length of time in the Southwest Theater of Operations during the Persian Gulf War, or • Served any length of time in Afghanistan, Syria, Djibouti or Uzbekistan on or after September 19, 2001 and • Manifests one of the following to any degree within 10 years from the date of separation from military service: o Asthma o Rhinitis o Sinusitis, to include rhinosinusitis 

Hoy hablamos de los herpes, ocho virus que provocan diferentes enfermedades y de los cuales casi todos portamos al menos uno. Herpes labial, genital, varicela, culebrilla, roséola, mononucleosis, sarcoma de Kaposi, Epstein-Barr... son muchos nombres, pero todos los virus que las provocan son de la misma familia. Hagamos un repaso sobre nuestros compañeros de vida indeseados.Entre capítulo y capítulo de Bacteriófagos os podéis mantener al día en cgdoval.es donde también encontraréis diferentes formas de apoyar a esta podcaster.

Sins Of Omission: The AZT Scandal By Celia Farber Spin Nov. 1989 On a cold January day in 1987, inside one of the brightly-lit meeting rooms of the monstrous FDA building, a panel of 11 top Aids doctors pondered a very difficult decision. They had been asked by the FDA to consider giving lightning-quick approval to a highly toxic drug about which there was very little information. Clinically called Zidovudine, but nicknamed AZT after its components, the drug was said to have shown a dramatic effect on the survival of Aids patients. The study that had brought the panel together had set the medical community abuzz. It was the first flicker of hope - people were dying much faster on the placebo than on the drug.  But there were tremendous concerns about the new drug. It had actually been developed a quarter of a century earlier as a cancer chemotherapy, but was shelved and forgotten because it was so toxic, very expensive to produce, and totally ineffective against cancer. Powerful, but unspecific, the drug was not selective in its cell destruction.  Drug companies around the world were sifting through hundreds of compounds in the race to find a cure, or at least a treatment, for Aids. Burroughs Wellcome, a subsidiary of Wellcome, a British drug company, emerged as the winner. By chance, they sent the failed cancer drug, then known as Compound S, to the National Cancer Institute along with many others to see if it could slay the Aids dragon, HIV. In the test tube at least, it did.  At the meeting, there was a lot of uncertainty and discomfort with AZT. The doctors who had been consulted knew that the study was flawed and that the long-range effects were completely unknown. But the public was almost literally baying at the door. Understandably, there was immense pressure on the FDA to approve AZT even more quickly than they had approved thalidomide in the mid-60s, which ended up causing drastic birth defects.  Everybody was worried about this one. To approve it, said Ellen Cooper, an FDA director, would represent a "significant and potentially dangerous departure from our normal toxicology requirements."  Just before approving the drug, one doctor on the panel, Calvin Kunin, summed up their dilemma. "On the one hand," he said, "to deny a drug which decreases mortality in a population such as this would be inappropriate. On the other hand, to use this drug widely, for areas where efficacy has not been demonstrated, with a potentially toxic agent, might be disastrous."  "We do not know what will happen a year from now," said panel chairman Dr. Itzhak Brook. "The data is just too premature, and the statistics are not really well done. The drug could actually be detrimental." A little later, he said he was also "struck by the facts that AZT does not stop deaths. Even those who were switched to AZT still kept dying."  "I agree with you," answered another panel member, "There are so many unknowns. Once a drug is approved there is no telling how it could be abused. There's no going back."  Burroughs Wellcome reassured the panel that they would provide detailed two-year follow-up data, and that they would not let the drug get out of its intended parameters: as a stopgap measure for very sick patients.  Dr. Brook was not won over by the promise. "If we approve it today, there will not be much data. There will be a promise of data," he predicted, "but then the production of data will be hampered." Brook's vote was the only one cast against approval.  'There was not enough data, not enough follow-up," Brook recalls. "Many of the questions we asked the company were answered by, 'We have not analyzed the data yet,' or 'We do not know.' I felt that there was some promising data, but I was very worried about the price being paid for it. The side effects were so very severe. It was chemotherapy. Patients were going to need blood transfusions. That's very serious.  "The committee was tending to agree with me," says Brook, "that we should wait a little bit, be more cautious. But once the FDA realized we were intending to reject it, they applied political pressure. At about 4 p.m., the head of the FDA's Center for Drugs and Biologics asked permission to speak, which is extremely unusual. Usually they leave us alone. But he said to us, 'Look, if you approve the drug, we can assure you that we will work together with Burroughs Wellcome and make sure the drug is given to the right people.' It was like saying 'please do it.'"  Brad Stone, FDA press officer, was at that meeting. He says he doesn't recall that particular speech, but that there is nothing 'unusual" about FDA officials making such speeches at advisory meetings. "The people in that meeting approved the drug because the data the company had produced proved it was prolonging life. Sure it was toxic, but they concluded that the benefits clearly outweighed the risks."  The meeting ended. AZT, which several members of the panel still felt uncomfortable with and feared could be a time bomb, was approved.  Flash forward: August 17, 1989. Newspapers across America banner-headlined that AZT had been "proven to be effective in HIV antibody-positive, asymptomatic and early ARC patients," even through one of the panel's main concerns was that the drug should only be used in a last-case scenario for critically-ill AIDS patients, due to the drug's extreme toxicity. Dr. Anthony Fauci, head of the National Institutes of Health (NIH), was now pushing to expand prescription.  The FDA's traditional concern had been thrown to the wind. Already the drug had spread to 60 countries and an estimated 20.000 people. Not only had no new evidence allayed the initial concerns of the panel, but the follow-up data, as Dr. Brook predicted, had fallen by the waysite. The beneficial effects of the drug had been proven to be temporary. The toxicity, however stayed the same.  The majority of those in the AIDS afflicted and medical communities held the drug up as the first breakthrough on AIDS. For better or worse, AZT had been approved faster than any drug in FDA history, and activists considered it a victory. The price paid for the victory, however, was that almost all government drug trials, from then on, focused on AZT - while over 100 other promising drugs were left uninvestigated.  Burroughs Wellcome stock went through the roof when the announcement was made. At a price of $8,000 per patient per year (not including blood work and transfusions), AZT is the most expensive drug ever marketed. Burroughs Wellcome's gross profits for next year are estimated at $230 million. Stock market analysts predict that Burroughs Wellcome may be selling as much as $2 billion worth of AZT, under the brand name Retrovir, each year by the mid-1990s - matching Burroughs Wellcome's total sales for all its products last year.  AZT is the only antiretroviral drug that has received FDA approval for treatment of AIDS since the epidemic began 10 years ago, and the decision to approve it was based on a single study that has long been declared invalid.  The study was intended to be a "double-blind placebo-controlled study," the only kind of study that can effectively prove whether or not a drug works. In such a study, neither patient nor doctor is supposed to know if the patient is getting the drug or a placebo. In the case of AZT, the study became unblinded on all sides, after just a few weeks.  Both sides of the contributed to the unblinding. It became obvious to doctors who was getting what because AZT causes such severe side effects that AIDS per se does not. Furthermore, a routine blood count known as CMV, which clearly shows who is on the drug and who is not, wasn't whited out in the reports. Both of these facts were accepted and confirmed by both the FDA and Burroughs Wellcome, who conducted the study.  Many of the patients who were in the trial admitted that they had analyzed their capsules to find out whether they were getting the drug. If they weren't, some bought the drug on the underground market. Also, the pills were supposed to be indistinguishable by taste, but they were not. Although this was corrected early on, the damage was already done. There were also reports that patients were pooling pills out solidarity to each other. The study was so severely flawed that its conclusions must be considered, by the most basic scientific standards, unproven.  The most serious problem with the original study, however, is that it was never completed. Seventeen weeks in the study, when more patients had died in the placebo group, the study was stopped short, and all subjects were put on AZT, no scientific study can ever be conducted to prove unequivocally whether AZT does prolong life.  Dr. Brook, who voted against approval, warned at the time that AZT, being the only drug available for doctors to prescribe to AIDS patients, would probably have a runaway effect. Approving it prematurely, he said, would be like "letting the genie out of the bottle."  Brook pointed out that since the drug is a form of chemotherapy, it should only be prescribed by doctors who have experience with chemotherapeutic drugs. Because of the most severe toxic effects of AZT - cell depletion of the bone marrow - patients would need frequent blood transfusions. As it happened, AZT was rampantly prescribed as soon as it was released, way beyond its purported parameters. The worst-case scenario had come true: Doctors interviewed by the New York Times later in 1987 revealed that they were already giving AZT to healthy people who had tested positive for antibodies to HIV.  The FDA's function is to weigh a drug's efficacy against its potential hazards. The equation is simple and obvious: A drug must unquestionably repair more than it damages, otherwise the drug itself may cause more harm than the disease it is supposed to fight. Exactly what many doctors and scientists fear is happening with AZT.  AZT was singled out among hundreds of compounds when Dr. Sam Broder, the head of the National Cancer Institutes (NCI), found that it "inhibited HIV viral replication in vitro." AIDS is considered a condition of immune suppression caused by the HIV virus replicating and eating its way into T-4 cells, which are essential to the immune system. HIV is a retrovirus which contains an enzyme called reverse transcriptase that converts viral RNA to DNA. AZT was thought to work by interrupting this DNA synthesis, thus stopping further replication of the virus.  While it was always known that the drug was exceedingly toxic, the first study concluded that 'the risk/benefits ratio was in favour of the patient."  In the study that won FDA approval for AZT, the one fact that swayed the panel of judges was that the AZT group outlived the placebo group by what appeared to be a landslide. The ace card of the study, the one that cancelled out the issue of the drug's enormous toxicity, was that 19 persons had died in the placebo group and only one in the AZT group. The AZT recipients were also showing a lower incidence of opportunistic infections.  While the data staggered the panel that approved the drug, other scientists insisted that it meant nothing - because it was so shabbily gathered, and because of the unblinding. Shortly after the study was stopped, the death rate accelerated in the AZT group. "There was no great difference after a while," says Dr. Brook, "between the treated and the untreated group."  "That study was so sloppily done that it really didn't mean much," says Dr. Joseph Sonnabend, a leading New York City AIDS doctor.  Dr. Harvey Bialy, scientific editor of the journal Biotechnology, is stunned by the low quality of science surrounding AIDS research. When asked if he had seen any evidence of the claims made for AZT, that it "prolongs life" in AIDS patients, Bialy said, "No. I have not seen a published study that is rigorously done, analyzed and objectively reported."  Bialy, who is also a molecular biologist, is horrified by the widespread use of AZT, not just because it is toxic, but because, he insists, the claims its widespread use are based upon are false. "I can't see how this drug could be doing anything other than making people very sick," he says.  The scientific facts about AZT and AIDS are indeed astonishing. Most ironically, the drug has been found to accelerate the very process it was said to prevent: the loss of T-4 cells.  "Undeniably, AZT kills T-4 cells [white blood cells vital to the immune system]" says Bialy. "No one can argue with that. AZT is a chain-terminating nucleotide, which means that it stops DNA replication. It seeks out any cell that is engaged in DNA replication and kills it. The place where most of this replication is taking place is the bone marrow. That's why the most common and severe side effect of the drug is bone marrow toxicity. That is why they [patients] need blood transfusions."  AZT has been aggressively and repeatedly marketed as a drug that prolongs survival in AIDS patients because it stops the HIV virus from replicating and spreading to healthy cells. But, says Bialy: "There is no good evidence that HIV actively replicates in a person with AIDS, and if there's isn't much HIV replication in a person with AIDS, and if there isn't much HIV replication to stop, it's mostly killing healthy cells."  University of California at Berkeley scientist Dr. Peter Duesberg drew the same conclusion in a paper published in the Proceedings, the journal of the National Academy of Sciences. Duesberg, whose paper addressed his contention that HIV is not a sufficient cause for AIDS, wrote: "Even if HIV were to cause AIDS, it would hardly be legitimate target for AZT therapy, because in 70 to 100 percent of antibody positive persons, proviral DNA is not detectable... and its biosynthesis has never been observed."  As a chemotherapeutic drug, explained Duesberg, explained Duesberg, AZT "kills dividing blood cells and other cells," and is thus "directly immunosuppressive."  "The cell is almost a million-fold bigger target than the virus, so the cell will be much, much more sensitive," says Duesberg. "Only very few cells, about one in 10,000 are actively making the virus containing DNA, so you must kill incredibly large numbers of cells to inhibit the virus. This kind of treatment could only theoretically help if you have a massive infection, which is not the case with AIDS. Meanwhile, they're giving this drug that ends up killing millions of lymphocytes [white blood cells]. It's beyond me how that could possibly be beneficial."  "It doesn't really kill them," Burroughs Wellcome scientists Sandra Lehrman argues. "You don't necessarily have to destroy the cell, you can just change the function of it. Furthermore, while the early data said that the only very few cells were infected, new data says that there may be more cells infected. We have more sensitive detection techniques now."  "Changes their function? From what - functioning to not functioning? Another example of mediocre science," says Bialy. "The 'sensitive detection technique' to which Dr. Lehrman refers, PCR, is a notoriously unreliable one upon which to base quantitative conclusions."  When specific questions about the alleged mechanisms of AZT are asked, the answers are long, contradictory, and riddled with unknowns. Every scientific point raised about the drug is eventually answered with the blanket response, "The drug is not perfect, but it's all we have right now." About the depletion of T-4 cells and other white cells, Lehrman says, "We don't know why T-4 cells go up at first, and then go down. That is one of the drug mechanisms that we are trying to understand."  When promoters of AZT are pressed on key scientific points, whether at the NIH, FDA, Burroughs Wellcome or an AIDS organization, they often become angry. The idea that the drug is "doing something," even though this is invariably followed with irritable admissions that there are "mechanisms about the drug and disease we don't understand," is desperately clung to. It is as if, in the eye of the AIDS storm, the official, government-agency sanctioned position is immunized against critique. Skepticism and challenge, so essential to scientific endeavour, is not welcome in the AZT debate, where it is arguably needed more than anywhere else.  The toxic effects of AZT, particularly bone marrow suppression and anemia, are so severe that up to 50 percent of all AIDS and ARC patients cannot tolerate it and have to be taken off it. In the approval letter that Burroughs Wellcome sent to the FDA, all of 50 additional side effects of AZT, aside from the most common ones, were listed. These included: loss of mental acuity, muscle spasms, rectal bleeding and tremors.  Anemia one of AZT's common side effects, is the depletion of red blood cells, and according to Duesberg, "Red blood cells are the one thing you cannot do without. Without red cells, you cannot pick up oxygen."  Fred, a person with AIDS, was put on AZT and suffered such severe anemia from the drug he had to be taken off it. In an interview in the AIDS handbook Surviving and Thriving With AIDS, he described what anemia feels like to the editor Michael Callen: "I live in a studio and my bathroom is a mere five-step walk from my be. I would just lie there for two hours; I couldn't get up to take those five steps. When I was taken to the hospital, I had to have someone come over to dress me. It's that kind of severe fatigue... The quality of my life was pitiful... I've never felt so bad... I stopped the AZT and the mental confusion, the headaches, the pains in the neck, the nausea, all disappeared within a 24-hour period."  "I feel very good at this point," Fred went on. "I feel like the quality of my life was a disaster two weeks ago. And it really was causing a great amount of fear in me, to the point where I was taking sleeping pills to calm down. I was so worried. I would totally lose track of what I was saying in the middle of a sentence. I would lose my directions on the street."  "Many AIDS patients are anemic even before they receive the drug." Says Burroughs Wellcome's Dr. Lehrman, "because HIV itself can infect the bone marrow and cause anemia."  This argument betrays a bizarre reasoning. If AIDS patients are already burdened with the problems such as immune suppression, bone marrow toxicity and anemia, is compounding these problems an improvement?  "Yes AZT is a form of chemotherapy." Says the man who invented the compound a quarter-century ago, Jerome Horowitz. "It is cytotoxic, and as such, it causes bone marrow toxicity and anemia. There are problems with the drug. It's not perfect. But I don't think anybody would agree that AZT is of no use. People can holler from now until doomsday that it is toxic, but you have to go with the results."  The results, finally and ironically, are what damns AZT. Several studies on the clinical effects of AZT - including the one that Burroughs Wellcome's approval was based on - have drawn the same conclusion: that AZT is effective for a few months, but that its effect drops of sharply after that. Even the original AZT study showed that T-4 cells went up for a while and then plummeted. HIV levels went down, and then came back up. This fact was well-known when the advisory panel voted for approval. As panel member Dr. Stanley Lemon said in the meeting, "I am left with the nagging thought after seeing several of these slides, that after 16 to 24 weeks - 12 to 16 weeks, I guess - the effect seems to be declining."  A follow-up meeting, two years after the original Burroughs Wellcome study, was scheduled to discuss the long range effects of AZT, and the survival statistics. As one doctor present at that meeting in May 1988 recall, "They hadn't followed up the study. Anything that looked beneficial was gone within half a year. All they had were some survival statistics averaging 44 weeks. The p24 didn't pan out and there was no persistent improvement in the T-4 cells."  HIV levels in the blood are measured by an antigen called p24. Burroughs Wellcome made the claim that AZT lowered this level, that is, lowered the amount of HIV in the blood. At the first FDA meeting, Burroughs Wellcome emphasized how the drug had "lowered" the p24 levels; at the follow-up meeting, they didn't mention it.  As that meeting was winding down, Dr. Michael Lange, head of the AIDS program at St. Luke's-Roosevelt Hospital in New York, spoke up about this. "The claim of AZT is made on the fact that it is supposed to have an antiviral effect," he said to Burroughs Wellcome, "and on this we have seen no data at all... Since there is a report in the Lancet [a leading British medical journal] that after 20 weeks or so, in many patients p24 came back, do you have any data on that?"  They didn't.  "What counts is the bottom line," one of the scientists representing Burroughs Wellcome summed up, "the survival, the neurologic function, the absence of progression and the quality of life, all of which are better. Whether you call it better because of some antiviral effect, or some other antibacterial effect, they are still better."  Dr. Lange suggested that the drug may be effective the same way a simple anti-inflammatory, such as aspirin, is effective. An inexpensive, nontoxic drug called Indomecithin, he pointed out, might serve the same function, without the devastating side effects.  One leading AIDS researcher, who was part of the FDA approval process, says today: "Does AZT do anything? Yes, it does. But the evidence that it does something against HIV is really not there."  "There have always been drugs that we use without knowing exactly how they work," says Nobel Prize winner Walter Gilbert. "The really important thing to look at is the clinical effect. Is the drug helping or isn't it?"  "I'm living proof that AZT works," says one person with ARC on AZT. "I've been on it for two years now, and I'm certainly healthier than I was two years ago. It's not a cure-all, it's not a perfect drug, but it is effective. It's slowing down the progression of the disease."  "Sometimes I feel like swallowing Drano," says another. "I mean, sometimes I have problems swallowing. I just don't like the idea of taking something that foreign to my body. But every six hours, I've got to swallow it. Until something better comes along, this is what is available to me."  "I am absolutely convinced that people enjoy a better quality of life and survive longer who do not take AZT," says Gene Fedorko, President of Health Education AIDS Liaison (HEAL). "I think it's horrible the way people are bullied by their doctors to take the drug. We get people coming to us shaking and crying because their doctors said they'll die if they don't take AZT. That is an absolute lie." Fedorko has drawn his conclusion from years of listening to the stories of people struggling to survive AIDS at HEAL's weekly support group.  "I wouldn't take AZT if you paid me," says Michael Callen, cofounder of New York City's PWA coalition, Community Research Initiative, and editor of several AIDS journals. Callen has survived AIDS for over seven years without the help of AZT. "I've gotten the shit kicked out me for saying this, but I think using AZT is like aiming a thermonuclear warhead at a mosquito. The overwhelming majority of long-term survivors I've known have chosen not to take AZT."  The last surviving patient from the original AZT trial, according to Burroughs Wellcome, died recently. When he died, he had been on AZT for three and one-half years. He was the longest surviving AZT recipient. The longest surviving AIDS patient overall, not on AZT, has lived for eight and one-half years.  An informal study of long-term survivors of AIDS followed 24 long-term survivors, all of whom had survived AIDS more than six years. Only one of them had recently begun taking AZT.  In the early days, AZT was said to extend lives. In actual fact, there is simply no solid evidence that AZT prolongs life.  "I think AZT does prolong life in most people," says Dr. Bruce Montgomery of the State University of New York City at Stony Brook, who is completing a study on AZT. "There are not very many long-tern survivors, and we really don't know why they survive. It could be luck. But most people are not so lucky."  "AZT does seem to help many patients," says Dr. Bernard Bahari, a New York City AIDS physician and researcher, "but it's very hard to determine whether it actually prolongs life."  "Many of the patients I see choose not to take AZT," says Dr. Don Abrams of San Francisco General Hospital. "I've been impressed that survival and lifespan are increasing for all people with AIDS. I think it has a lot to do with aerosolized Pentamidine [a drug that treats pneumocystis carinii pneumonia]. There's also the so-called plague effect, the fact that people get stronger and stronger when a disease hits a population. The patients I see today are not as fragile as the early patients were."  "Whether you live or die with AIDS is a function of how well your doctor treats you, not of AZT," says Dr. Joseph Sonnabend, one of New York's City's first and most reputable AIDS doctor, whose patients include many long-term survivors, although he has never prescribed AZT. Sonnabend was one of the first to make the simple observation that AIDS patients should be treated for their diseases, not just for their HIV infection.  Several studies have concluded that AZT has no effect on the two most common opportunistic AIDS infections, Pneumocystic Carinii Pneumonia (PCP) and Kaposi's Sarcoma (KS). The overwhelming majority of AIDS patients die of PCP, for which there has been an effective treatment for decades. This year, the FDA finally approved aerosolized Pentamidine for AIDS. A recent Memorial Sloan Kettering study concluded the following: By 15 months, 80% of people on AZT not receiving Pentamidine had a recurring episode. "All those deaths in the AZT study were treatable," Sonnabend says. "They weren't deaths from AIDS, they were deaths from treatable conditions. They didn't even do autopsies for that study. What kind of faith can one have in these people?"  "If there's any resistance to AZT in the general public at all, it's within the gay community of New York," says the doctor close to the FDA approval, who asked to remain anonymous. "The rest of the country has been brainwashed into thinking this drug really does that much. The data has all been manipulated by people who have a lot vested in AZT."  "If AIDS were not the popular disease that it is - the money-making and career-making machine - these people could not get away with that kind of shoddy science," says Bialy. "In all of my years in science I have never seen anything this atrocious." When asked if he thought it was at all possible that people have been killed as a result of AZT poisoning rather then AIDS he answered: "It's more than possible."  August 17, 1989: The government has announced that 1.4 million healthy, HIV antibody-positive Americans could "benefit" from taking AZT, even though they show no symptoms of disease. New studies have "proven" that AZT is effective in stopping the progression of AIDS in asymptomatic and early ARC cases. Dr. Fauci, the head of NIH, proudly announced that a trial that has been going on for "two years" had "clearly shown" that early intervention will keep AIDS at bay. Anyone who has antibodies to HIV and less than 500 T-4 cells should start taking AZT at once, he said. That is approximately 650,000 people. 1.4 million Americans are assumed HIV antibody-positive, and eventually all of them may need to take AZT so they don't get sick, Fauci contended.  The leading newspapers didn't seem to think it unusual that there was no existing copy of the study, but rather a breezy two-pages press release from the NIH. When SPIN called the NIH asking for a copy of the study, we were told that it was "still being written." We asked a few questions about the numbers. According to the press release, 3,200 early AARC and asymptomatic patients were devided into two groups, one AZT and one placebo, and followed for two years. The two groups were distinguished by T-4 cell counts; one group had less than 500, the other more than 500. These two were then divided into three groups each: high-dose AZT, low-dose AZT, and placebo. In the group with more than 500 T-4 cells, AZT had no effect. In the other group, it was concluded that low-dose AZT was the most effective, followed by high-dose. All in all, 36 out of 900 developed AIDS in the two AZT groups combined, and 38 out of 450 in the placebo group. "HIV-positive patients are twice as likely to get AIDS if they don't take AZT," the press declared.  However, the figures are vastly misleading. When we asked how many patients were actually enrolled for a full two years, the NIH said they did not know, but that the average time of participation was one year, not two.  "It's terribly dishonest the way they portrayed those numbers," says Dr. Sonnabend. "If there were 60 people in the trial those numbers would mean something, but if you calculate what the percentage is out of 3,200, the difference becomes minute between the two groups. It's nothing. It's hit or miss, and they make it look like it's terribly significant."  The study boasted that AZT is much more effective and less toxic at one-third the dosage than has been used for three years. That's the good news. The bad news is that thousands have already been walloped with 1,500 milligrams of AZT and possibly even died of toxic poisoning - and now we're hearing that one third of the dose would have done?  With all that remains so uncertain about the effects of AZT, it seems criminal to advocate expanding its usage to healthy people, particularly since only a minuscule percentage of the HIV-infected population have actually developed ARC or AIDS.  Burroughs Wellcome has already launched testing of AZT in asymptomatic hospital workers, pregnant women, and in children, who are getting liquid AZT. The liquid is left over from an aborted trial, and given to the children because they can mix it with water - children don't like to swallow pills. It has also been proposed that AZT be given to people who do not yet even test positive for HIV antibodies, but are "at risk."  "I'm convinced that if you gave AZT to a perfectly healthy athlete," says Fedorko, "he would be dead in five years."  In December 1988, the Lancet published a study that Burroughs Wellcome and the NIH do not include in their press kits. It was more expansive than the original AZT study and followed patients longer. It was not conducted in the United States, but in France, at the Claude Bernard Hospital in Paris, and concluded the same thing about AZT that Burroughs Wellcome's study did, except Burroughs Wellcome called their results "overwhelmingly positive," and the French doctors called theirs "disappointing." The French study found, once again, that AZT was too toxic for most to tolerate, had no lasting effect on HIV blood levels, and left the patients with fewer T-4 cells than they started with. Although they noticed a clinical improvement at first, they concluded that "by six months, these values had returned to their pretreatment levels and several opportunistic infections, malignancies and deaths occurred."  "Thus the benefits of AZT are limited to a few months for ARC and AIDS patients," the Fench team concluded. After a few months, the study found, AZT was completely ineffective.  The news that AZT will soon be prescribed to asymptomatic people has left many leading AIDS doctors dumbfounded and furious. Every doctor and scientist I asked felt that it was highly unprofessional and reckless to announce a study with no data to look at, making recommendations with such drastic public health implications. "This simply does not happen," says Bialy. "The government is reporting scientific facts before they've been reviewed? It's unheard of."  "It's beyond belief," says Dr. Sonnabend in a voice tinged with desperation. "I don't know what to do. I have to go in and face an office full of patients asking for AZT. I'm terrified. I don't know what to do as a responsible physician. The first study was ridiculous. Margaret Fishl, who has done both of these studies, obviously doesn't know the first thing about clinical trials. I don't trust her. Or the others. They're simply not good enough. We're being held hostage by second-rate scientists. We let them get away with the first disaster; now they're doing it again."  "It's a momentous decision to say to people, 'if you're HIV-positive and your T4-cells are below 500 start taking AZT,'" says the doctor who wished to remain anonymous. "I know dozens of people that I've seen personally every few months for several years now who have been in that state for more than five years, and have not progressed to any disease."  "I'm ashamed of my colleagues," Sonnabend laments. "I'm embarrassed. This is such shoddy science it's hard to believe nobody is protesting. Damned cowards. The name of the game is protect your grants, don't open your mouth. It's all about money... it's grounds for just following the party line and not being critical, when there are obviously financial and political forces that are driving this."  When Duesberg heard the latest announcement, he was particularly stunned over the reaction of Gay Men's Health Crisis President Richard Dunne, who said that GMHC now urged "everybody to get tested," and of course those who test positive to go on AZT. "These people are running into the gas chambers," says Duesberg. "Himmler would have been so happy if only the Jews were this cooperative." 

The rock band who opened for System of a Down Saturday at the Save Mart Center in Fresno had all of their equipment stolen.The Chicago band, Russian Circles, got burglarized at the Holiday Inn in Chowchilla. The American Food and Drug Administration has approved a groundbreaking, complex, generic drug indicated for the treatment of ovarian cancer, multiple myeloma and Kaposi's Sarcoma. Hacker RootAyyildiz took credit for the earlier hacking of the former president's donaldjtrump.com website. See omnystudio.com/listener for privacy information.

Ce 4ème mini-épisode hors-série entend combiner l'identité arabo-musulmane en France et la séropositivité au VIH. C'est un sujet qui me tient très à cœur et pour lequel il est indispensable d'effacer les stéréotypes. Selon l'ONU, 1,7 million de personnes ont contracté le VIH l'an dernier et plus de 40 millions de personnes vivent avec actuellement. Je ne vais pas vous faire un exposé sur les trithérapies, les sarcomes de Kaposi, l'inhibiteur de protéase ou l'épidémiologie historique de la maladie. Je vais plutôt vous montrer en quoi il est insoutenable de vivre avec son symptôme le plus persistant : la sérophobie.  On m'a dit « elle je la touche pas avec un bâton, ça s'voit elle a l'DAS ». On a dit « regarde sa gueule à lui, il prend tellement cher qu'on dirait un zombie sidatique ». On m'a dit que « si j'avais le SIDA, ce serait de ma faute et qu'on viendra pas me soutenir à l'hôpital. ». On dit « si t'as le SIDA, c'est que t'es sûrement pédé ».  Toutes ces remarques odieuses, c'est purement et simplement de la sérophobie, c'est-à-dire le rejet et la discrimination des personnes séropositives. Il existe une réelle discrimination sociale de la part de l'entourage, de l'employeur, du corps médical et des institutions… comme c'est bizarre, on dirait qu'on parle de ce que subissent certaines personnes musulmanes ou racisées ! Rappelons que Jean-Marie Le Pen voulait créer des « sidatoriums » pour isoler les porteurs du VIH et les traiter hors du cadre médico-hospitalier, des camps qui rappellent d'autres camps de la mort. En Égypte, plusieurs personnes porteuses du virus ont été incarcérées arbitrairement depuis 2007 pour la simple raison qu'elles étaient séropositives… Alors oui, il faut parler de l'intersectionnalité entre islam, culture arabe et cette sérophobie latente dont souffre les personnes qui vivent avec le VIH ou le SIDA.  En France, 173 000 personnes vivent avec le VIH. 24 000 ignorent qu'ils sont porteurs. 1/4 découvrent leur séropositivité trop tard. Un quart des 15-24 ans (24%) pensent encore que le virus du Sida peut se transmettre par un baiser (ce qui est faux), selon un sondage mené en 2021 par l'Ifop. Bon alors, comment déconstruire la peur du VIH ? Comment éviter les conséquences psychologiques de la sérophobie sur les personnes concernées : rejet, exclusion, moqueries, discriminations ? Est-ce qu'il y a des similitudes entre sérophobie, islamophobie et racisme ? Est-ce Allah qui nous punit de nos actes de fornication ? Si vous voulez bouquiner

Dr. Hayes interviews Dr. Breitbart on his research addressing psychiatric, psychological and existential adjustment as well as symptom control in advanced cancer.   TRANSCRIPT SPEAKER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL HAYES: Welcome to JCO's Cancer Stories-- The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insights into the world of cancer care. You can find all of their shows, including this one, at podcast.asco.org. We have a special treat today in our podcast series in that I have the opportunity to interview Dr. William Breitbart. Dr. Breitbart is the Jimmie Holland Chair of Oncology at Memorial Sloan Kettering and the Professor and Vice Chair of the Department of Psychiatry at the Weill Cornell Medical College. And as far as I can see, Dr. Breitbart, you've never left New York City. But I will get the background. And you can tell us if you took a vacation or something one time outside the city. Dr. Breitbart grew up in the Lower East Side of Manhattan. He went to Brooklyn College, graduated in 1973, then medical school at the Albert Einstein College of Medicine. And then he did his residency in internal medicine at the Bronx Hospital and trained basically at Memorial Sloan Kettering. Joined the faculty there, and has been on the faculty ever since. He has a number of accomplishments, too many for me to really review it carefully. But he's been president of the International Psycho-Oncology Society and received their Sutherland Lifetime Achievement Award. He's been president of the Academy of Psychosomatic Medicine and received their Hackett Lifetime Achievement Award. And on a personal basis, my brother was also the president of the Academy of Psychosomatic Medicine. So I'm very proud of my brother and equally proud of Dr. Breitbart. He really is responsible for a number of enormous steps forward in our field, including psychotherapeutic approaches for palliative care of patients with terminal illnesses, especially cancer. He has been involved with what I saw you call, Dr. Breitbart, "hastened to death." I had learned it as assisted suicide. I'm going to ask you a question about that. I'm interested in your comments. And more recently, meaning-centered psychotherapy for the terminally ill And we'll talk more about that, too. So in addition, I have asked Dr. Breitbart if he would also give us insights into Dr. Jimmie Holland's life and her career. Sadly, she passed away before we had an opportunity to chat with her. She was one of my favorite people in the whole world. And I think everybody that knew here said the same thing. So we'll get some insights for those of you who didn't know Dr. Holland from this call as well. Before we start, Dr. Breitbart wants to declare that he's received honoraria from Novartis and has a consulting or advisory role with Novartis. Dr. Breitbart, welcome to our program today. WILLIAM BREITBART: Thank you Dr. Hayes, pleasure to be here. Can I make just one slight correction? I actually trained in both internal medicine and psychiatry at the Bronx Municipal Hospital, which is the Albert Einstein College of Medicine, in New York City Health and Hospitals Corporation's Public Hospital. So I trained in both psychiatry and internal medicine, jumping back and forth between the two, out of a state of confusion. And then I landed in Dr. Holland's fellowship at Memorial Sloan Kettering for a variety of reasons. The main reason was though that I had developed a thyroid cancer when I was a medical resident in the middle of my training. And then I went back to finish up more of my psychiatry residency training, I became the liaison to the Oncology Clinic at Jacobi Hospital, the Bronx Municipal Hospital. I did consultations for cancer patients. I ran groups for cancer patients and also ran groups for the oncologists and oncology nurses. And I was trying to educate myself on the subject of psycho-oncology or psychiatric oncology. It actually hadn't been named yet in those days. And the only literature I could find were papers written in oncology journals by Dr. Julie Holland. And so that's where I knew where I needed to go to become more expert in this area. That's the most superficial version of how I ended up at Memorial Sloan Kettering. I could tell you the more interesting version if you're interested. DANIEL HAYES: Well, actually, what you just covered was my first question. I was going to say this is about you, not about me. But my brother also did training in internal medicine and decided to go in psychiatry, and ended up in psychiatry liaison. And I think that's what makes you two, and others like you, powerful, is that if you go to France and you don't speak French, you're not going to be listened to. And if you come to a bunch of oncologists, and you don't speak internal medicine or oncology, we're not going to listen to you. And I think clearly to me, Jimmie Holland always knew what I did. And I think you have the same strength. I'd love to hear how you actually got involved with her. Yes. Please begin. WILLIAM BREITBART: I agree with you actually about that comment. It's very helpful to have had the training in both medicine and psychiatry. And, in fact, we've trained a few fellows who've done oncology fellowships and then done our-- and a psychiatry residency and then done our psycho-oncology fellowship as well. But the real story of how I ended up in this field starts in childhood, where a lot of stories start. But my parents were both Holocaust survivors from Eastern Europe, from Poland in particular. When the war broke out, my mother was 14 years old and my father was 17 years old. And my father's family were all killed. But he ended up surviving, hiding in the woods. And he became-- Polish forest-- and he became part of a partisan fighter group, lived in the Polish forest. And one day he went looking for food and broke into this farmhouse. And as it turned out, my mother and her parents were being hidden by a Catholic woman, who hid them in a hole underneath the stove in her barn. And my father broke into this farmhouse and discovered my mother and my maternal grandparents. It turned out they were related. They were second cousins. My father said, you can't stay here. It's not safe. You should come into the woods with me and 150 other people. My grandparents were too afraid to go. But they let my mother go. So at the tender age of 14 and 17, my parents were hiding in the Polish forest, where they lived for about three years, hiding from the Nazis, and then Ukrainians, and all sorts of people who were interested in killing Jews. And they finally, after the war, crossed over to Germany. They actually found my grandparents alive. And they crossed over the border to Germany, went into this displaced persons' camp outside of Munich and got married there. And then came to the Lower East Side in late 1949, early 1950. And I was born several years later. And I grew up in this home on the Lower East Side, as you pointed out. And I grew up in a home where the Holocaust also lived. I lived in this home where the Holocaust was in every room-- didn't have a room of its own. It was in all the rooms, on all the walls-- and all the pictures that had been saved of my family, that had perished, on all the religious articles that might have been saved, et cetera. So I grew up in this environment where I understood at a very early age, maybe four or five years old, that death and suffering were very real. And that we all lived in this space between life and death. My mother would ask me every morning-- when she gave me breakfast, she would ask me the question, why am I here? And the full question really was, why am I here and everyone else is dead? Basically, what evolved out of this was the transmission of this responsibility or I guess a burden-- for me, it was an inspiration-- for me to accomplish something of such significance and impact-- in the world of suffering in particular-- in the arena of people who suffer in the face of death. And it's going to be up to me to achieve something of such significance that my parents would be able to-- my mother would be able to turn around and say, well you see we had to survive because if I hadn't survived, there wouldn't be Bill Breitbart in the world. [LAUGHTER] So that was the mission. That was the burden. That was the inspiration. And I wasn't fully cognizant of it. But I was traveling this journey-- this route that took me through college, and loving science and poetry, ending up in medical school, thinking I'd be a psychiatrist, but then falling in love with medicine. Loving both psychiatry and medicine. What I realized what fascinated-- what fascinated me was how a human being can live a mortal, finite life. How do you-- as a person who develops a life-threatening illness, how do you continue to live? How do you have the strength, the courage, to keep on living? And what gives you purpose and meaning? And so I got myself to Sloan Kettering by reading the work of Dr. Jimmie Holland and Dr. Massie. And I found myself at Memorial. I put myself in a place, with a mentor-- a group of mentors-- a place where I would breathe the same air of my patients, who were breathing the air of a human being confronting death, confronting the real prospect death being closer than-- closer than it was farther away. So that's how I ended up at Memorial. That's the real story. And I went to Sloan Kettering to do a fellowship, just to become a good clinician. I wanted to be a clinician. I never had the expectation of being a clinical researcher or an academician. I never had the ambition or aspiration to be an academic, a teacher, an advocate; never thought to be a professor of anything. I never thought I'd write books, or scientific articles, or become president of organizations, et cetera. All that happened because of my exposure to Jimmie. And my interest in research ended up being a result of one conversation that I had as a fellow. Dr. Holland, who was supposed to be my supervisor-- she's deceased now-- she was my inpatient supervisor-- my outpatient, inpatient supervisor. So we made rounds one day, which was very rare. But we made rounds one day. And I was the liaison. I was very fortunate enough to be the liaison to the Neuro-Oncology Unit and to the Pain Service at Memorial, which were both within the Department of Neurology. When Dr. Holland was recruited to Memorial Sloan Kettering in 1977, it was by the chair of the Department of Neurology, Dr. Jerome Posner-- Jerry Posner-- who recruited both Jimmie to be the Chief of the Psychiatry Service and he recruited Kathy Foley to be the Chief of the Pain Service. So I basically held on to these two meteoroids. Jimmie Holland and Kathy Foley, those are the two people who helped-- helped pull me along the road. So on the Neuro-Oncology Unit, I had done a consult on patient with brain tumors, on high-dose steroids. And he had a severe psychosis. And I asked Dr. Holland, why is it that these patients on steroids develop these neuropsychiatric syndromes? They develop depressions. And they can get delirious, and psychotic, and manic. And this was the advice that my mentor gave me-- Dr. Holland gave me-- which turned me into a scientist. And her response was, well, gee, Bill-- in her Texas twang-- well, gee, Bill, I really don't know. I really don't know. I guess you'll just have to go figure that one out yourself. [LAUGHTER] And that's what I ended up doing. I then pursued figuring it out myself. And that's what I did for the next 30 years, trying to figure out clinical problems-- when the AIDS epidemic exploded. My first research study was to study looking at patients with epidural spinal cord compression, those who had high grade versus lower grade compression. One group got high-dose steroids, the other didn't. And I did a comparison study of psychiatric syndromes in both populations. I was at Memorial when the AIDS epidemic exploded. And so I started to do studies of delirium. I did the first double-blind randomized controlled trial of neuroleptics for the treatment of delirium in the AIDS population because they all got demented and delirious. I did the first studies of pain in HIV. I did the first studies of desire for hastened death in patients with advanced AIDS and in patients with advanced cancer. And then I started to do a lot more work in inflammation and depression in pancreatic cancer patients. And eventually, everything kind of culminated. As I evolved from being a psychiatric oncologist to a psychiatric oncologist and palliative care clinician, that kind of bridged the two worlds of psychopharmacology and palliative care. And I started really looking at issues of desire for hastened death and the loss of meaning. And then developed interventions for meaning, which we call meaning-centered psychotherapy, which has been a real advance I think in our field. DANIEL HAYES: You must have been Dr. Holland's first trainee at Memorial. WILLIAM BREITBART: Well, her story-- basically, she was this young country girl in Nevada, Texas. She grew up on a farm, a cotton farm apparently. She was most influenced by the country doctor who would visit when people were ill. And when he passed away, he gave her a set of medical books, which inspired her. And she told her family, I think I want to be a doctor. And they said, well, gee, that sounds unreasonable, Jimmie. But whatever you feel like doing, go ahead. She ended up going to Baylor. And I think she was one of only three women in medical school class at Baylor. She started her residency I think at Baylor as well. And then eventually, she got married. Her first husband died tragically. I believe it was a suicide, which I think got interested in psychiatry. She ended up, I think, doing her residency at-- finishing her residency at MGH, along with Tom Hackett, people like that. And somewhere along that route, that's where she met James Holland. So James and Jimmie were, as you say, a power couple. James told me that Jimmie was his secret weapon, his secret power. But Jimmie told me the exact same thing about James. I think they fed off each other in terms of creativity and ideas. So when James moved to Roswell Park, I guess, Jimmie started a special clinic. And she called it "special" because nobody would come to a psychiatry clinic. But they would come to a place that was special because it made them feel special. And I guess it was around that time that James started collaborators-- CALGB. On the drive to work one day, Jimmie said, you ask patients every kind of question, like how many bowel movement does he have? You're very invasive in your questions. But you never ask them how they feel. And so she insisted that James do something about that. And so in order I guess to not get nagged on the car ride every day, he started a quality of life committee in CALGB. And Jimmie chaired that for quite a while. Eventually, I think James went to Mount Sinai. And Jimmie came along. And she worked at Albert Einstein-- College Hospital-- at Boston College of Medicine. And she was there with actually a bunch of pioneers of psychosomatic medicine. There was a guy named Herb Weiner, and Sig Ackerman, and Jim Strain, and Myron Hofer. These are very important names in our field of psychosomatic medicine. Jerry Posner at Memorial, Department of Neurology, was looking to bring psychiatry into-- consultative service to Sloan Kettering. And Jimmie often says they couldn't get Ned Cassem from MGH. So they picked her in second tier. And in 1977, she came there, along with a resident who graduated from Einstein, Mary Jane Massem. And the two of them had an office, with a card table-- as she described-- and a stack of index cards with the patients on them. And they set about starting a consult service. So in '77, she was the chief of the psychiatry service. And then about '78 or '9, a clinical fellowship was established. The NIMH had an initiative at that point to develop consultation liaisons, psychosomatic medicine fellowships around the country. And so she benefited from that initiative, and started a fellowship. That continued through '78 or so. And there are a couple of classes of fellows before me. I came to do the fellowship 1984 to '86. And it was during my fellowship, I think, that Jimmie and a woman named Julia Rowland, a psychologist, who's at the Smith Center now-- but was around the NCI's survivorship program for a long time. DANIEL HAYES: I actually worked with Julia at Georgetown for five years. WILLIAM BREITBART: At Georgetown, exactly. So she and Julia wrote the first-- edited the first textbook of psycho-oncology. It was called the Handbook of Psychooncology. And that's the first time I think the term "psychooncology" was used. I think it might have been 19-- late 1980s. It might have been 1989 or so that book came out. And the term psychooncology was not hyphenated at that point. There was no hyphen between the two O's. Jimmie asked me to write about six chapters. I knew a lot about delirium. I wrote that chapter. I knew a lot about suicide and cancer, which was an early interest of mine. And I knew a lot about neuropsychiatric issues and AIDS. But I didn't know very much about neuroendocrine phenomena that caused neuropsychiatric syndromes or the psychiatric aspects of head and neck cancer. I said to Jimmie, I don't know anything about these subjects, Jimmie. Do you think I'm the person to write this chapter? And she said to me, well, Bill, there are no experts in the world in this field. [LAUGHTER] So after you write the chapter, you will be the expert. So that was the philosophy. And so as a mentor, I would basically say the greatest thing about her as a mentor was that she gave you the confidence that you could achieve whatever you wanted-- whatever you were driven to achieve. She had that faith in you. The idea was that the only person who really had to believe in what you were doing was you. And if it was important to you to find the answer to that question, that you would be able to do it. She had a knack for finding people who were very driven, who joined this mission. It was really a mission. It was a calling to provide the human side of cancer care, to provide whole person care, to take care of the person who had cancer while they were going through all the cancer treatments. And the combination therapies that James Holland had come up with. DANIEL HAYES: Two stories about Jim, who I had more association than with Jimmie. Although Jimmie told me the thing she tell you, which is you got to figure out what you want to do. And then you'll be great at it, because I wasn't sure. But with Jim Holland, two things. I was the very young guy in a field to be. And I was named chair one of the committees. And he was sitting in the back. And I was talking about, well, we need a statistical plan, and that sort of thing. And in the back of the room, as only he could do without a microphone, "Well, Hayes, if you need a statistician, it's probably not worth doing." And other is, I once asked him, between you and Dr. Frye, who was my boss, Dr. Frye White-- the three guys, who actually came up with the idea of combinational therapy? And I might as well have let a fuse to a bomb because he was-- "Well, I did. I was there before they did. They came in. They were in the minority." And he sent me the protocol. That was David. So to be sure I understood that he had written it before those guys got there. He was quite a character. And I have to say, your comments about Jimmie, and being married to Jim, were like oil and water. It's unbelievable to me that they actually had a very loving, long-term relationship. She had five children with him, who are all accomplished in their own right. WILLIAM BREITBART: Yes, they are. DANIEL HAYES: And they just they just managed to make it work because he could be hard to deal with. But everybody loved him because of it. WILLIAM BREITBART: Yeah. I think the secret ingredient there is dedication. They were both people of great dedication and commitment. And they were committed to two things. They were committed to the work they did. And they were committed to each other and their family. And so I think that was the secret-- the secret ingredient. DANIEL HAYES: There are a number of things in your own career that struck me as I was going through it. That one of my own interests would be your work with hastened death. And again, I actually wrote a little sort of term paper kind of thing on this. And it was called assisted suicide. And I think we're talking about the same thing. Talk more about that, and what you've been involved with, and where you think that's going. WILLIAM BREITBART: Right. Well, my interest in that all started during the AIDS crisis, the AIDS epidemic, in the mid-'80s to mid-'90s or so. And I was right in the thick of it, in Manhattan, in New York City. And Sloan Kettering had a large population of AIDS patients, because of their interest in Kaposi's sarcoma and lymphomas. And they ended up taking care of a lot of patients. And I saw a lot of patients. And I was that age-- I was often the age of the patients-- many of the patients who I was treating. It was very difficult work, but very inspiring work. You really felt like you were doing important work, obviously. And because of many of the patients were younger men, men in their 30s, who I could relate to in many ways-- like you, I'm sure there are many patients that you treat. There are some that you feel closer to, you identify a lot more with, right. And these were-- that was the case here. And at the time, I was treating patients with AIDS. And there was no treat-- there was no therapy at all. And people were dying very difficult deaths. And I had many, many patients who asked me if I could help them die, if I could assist them in the suicide, could I prescribe their medicine, could I somehow hasten their death? And so for me, it was a clinical problem. What do I do? How do I understand this? What drives this desire to hasten your death? I knew it came out of a sense of despair. I knew it came out of a distress and a sense of despair. But at the time that this was happening, clinically there was also a big debate in our society about legalization of assisted suicide. And, in fact, I think that was the Supreme Court case of Vacco versus Quill, which was also being adjudicated at that time. And states, like Oregon, were starting to have a referendum about whether to legalize these things. So I thought, does one create policies based on popular opinion, or whatever, or a public opinion? Or do you create policies by understanding of the problem and that's informed by research? So I thought I needed to understand this. If I was going to be helpful as a psychiatrist, in this kind of a setting. And it came up occasionally with cancer patients, too. But it was just so dramatic. And it confronted me for the first time, mainly during the AIDS crisis. I felt I needed to understand it more, so that I could know how to be helpful or useful. Was I going to be able to eliminate the suffering? Or was my only option to eliminate the sufferer? And so we set about doing a set of studies, both in terminally ill AIDS patients and terminally ill cancer patients. And I actually developed and validated a scale that measured desire for hastened death. It's called the Schedule of Attitudes towards Hastened Death. Up until that point, people didn't really have a way of measuring it. They just asked the patient, yes or no, do you have-- or they might qualify it on a 0 to 4 scale or something. And so what was really interesting-- and one of my early fellows, my first fellow, the first surgeon attending from oncology, Chasnoff, who went back to Canada-- Winnipeg. And he starts to do a study. He did studies around the same time. But he didn't have a validated measure. But we ended up finding very similar things. As it turned out, about 40%-- 45% of folks who had high desire for hastened death, had a depression. About 17% of patients that had cancer-- we'll stick to the cancer data. About 17% of cancer patients have a high desire for phase. These are patients with advanced cancer, in a palliative care unit, or a hospice, whatever. And about 45% of those patients have a depression that was undiagnosed, untreated. The other factors that seem to contribute to desire for hastened death were things like lack of social support, uncontrolled pain, and severe physical debilitation. So I said, well, we can treat pain. We can increase social support. I gave a presentation one day at-- Kathy Foley had worked with George Soros and the Open Society Institute, to develop something called Project on Death in America. And I gave a talk to the board of the Project on Death in America. I was in the class of the first faculty scholars of Project on Death in America. It included a lot of people who are at the forefront of palliative care these days. But I gave a talk on this, on patient death. And one of the ethicists in the room, a famous ethicist, asked me, well, what happens to desire for hastened death if you treat the depression? And before answering that question, I said to myself, make a mental note. That's your next ROI grant, Bill. And so what I did after that, is I wrote several grants and did two studies looking at what treating depression in patients with high desire for hastened death. And I did both in AIDS and cancer patients, terminal cancer patients, two different studies. As it turns out, if you treat-- if someone who has high desire for hastened death and they have a depression, and you treat the depression, 90% of those patients, when their depression remits, the desire for hastened death remits. But there was still this segment of population of advanced cancer patients, were not depressed, did not have uncontrolled pain, or lack of social support. There were about a 40%-- 35%, 40% of the group, I didn't have the element, the factor that contributed to this desire for hastened death. So I figured there's something there that I haven't found. So we went back and did further studies. And we looked at other variables, like anxiety, hopelessness, loss of meaning. And what we discovered was that hope of hopelessness and loss of meaning were independent and synergistic factors that contributed to the desire for hastened death, and made up an additional 30% of the so-called variance. So between depression and hopelessness, independent of depression, and loss of meaning independent of depression, you could account for about 85%, 90% of the reasons why patients wanted to desire for hastened death. Based on my research and the research of others, there's still about a 10% group who are probably not in great despair. But the issue for them is, I live my life in a pretty authentic way. I've been able to control how I live my life. I should be able to. And I want to control the circumstances of my death. And they're not impaired by depression or anything like that. But when we had the findings of hopelessness and loss of meaning, I said to myself, OK, now I've got to find an intervention for loss of meaning and hopelessness. And I was looking for a drug. I went through every page of the PDR. And there was no drug for loss of meaning or loss of hope. So I had to turn to psychotherapy. Our CL psychiatrist-- you know, psychosomatic medicine psychiatrists, we like to give drugs. If there's a drug solution, we've got it. I'm your guy. So I had to force myself to turn towards psychotherapy rather later in my career, after doing all of these stimulant trials for fatigue and things like that, and other pharmacological trials for pain-- neuropathic pain, et cetera, delirium trials. There I was, starting to figure out what kind of psychotherapy can I develop to help enhance sense of meaning and hope? And that's when I turned to, ironically, a Holocaust survivor named Victor Frankl-- and turned to the work of Victor Frank, who wrote the book, Man's Search for Meaning. His big idea was that meaning is a primary motivating force for human behavior, similar to the idea of libido, and instinctual drive, and things like that. He thought meeting was another important drive. "Better" instinctual, he called it. And he thought that there were predictable sources of meaning that one could tap into. And so we basically developed-- just sat down in a room with a couple of my fellows. And we hacked out a seven-- or at the beginning, it was group intervention. So it was an eight-session intervention. And then we developed an individual format, seven sessions. And we basically developed this brief, structured psychotherapy that involved teaching patients the importance of meaning, both didactically and experientially; teaching them the various sources of meaning; and relating it to their cancer experience and living with cancer. And the whole purpose was to be able to get through cancer, and even facing death, by sustaining a sense of meaning for as long as you possibly could. And that's what we called meaning-centered psychotherapy. I ended up doing four randomized-- NIH-funded, randomized controlled trials of both individual and a group format. And now we have a-- we're in the seventh year of an R25 training grant. We're training a national and international cohort of clinicians to provide meaningful psychotherapy in the manuals and textbooks that are published. DANIEL HAYES: I'd like to segue this-- WILLIAM BREITBART: [INAUDIBLE], I designated it as a evidence-based intervention for palliative care. DANIEL HAYES: Well, I'd like to segue, that as you were talking, most of people listening to this are probably medical oncologists. And my impression is, we don't get a lot of this training that you're talking about. And the people you're training, they're probably a psychiatrist, not a medical oncologist. How have you translated that over to our world? WILLIAM BREITBART: Now, so actually the people we're training-- a few psychiatrists, not too many. We train psychiatrists, social workers, nurses, nurse practitioners, oncology nurse practitioners, oncology nurses, oncologists, chaplains, palliative care docs. We're expanding the training. And it's quite simple. And it's actually-- but we're working with a group to develop this into a digital app. It might be able to be prescribed by oncologists so that you don't even need a therapist. DANIEL HAYES: Are you in the weeds with the medical oncologists at Memorial, at Sloan. I mean, do you make rounds with them and help train them? WILLIAM BREITBART: Yeah. Jimmie started out with one psychiatrist. By the time the Psychiatry Service became a department in 1996, I think there were 12 psychiatrists and psychologists. And as of last count, I think we have 43 faculty, 25 psychiatrists and the rest psychologists, and around 200 staff, including research staff, and research faculty, and psychiatry services. So I took over as chief when Jimmie became the first chair in the Behavioral Sciences Service. And we had a cancer disparities in the Immigrant Health Service. So it's grown quite a bit. And all of us, we work in a sort of a disease management embedded model. So I originally was the psychiatrist for the Neuropsychology and Pain Service, and moved to the hepato-pancreato-biliary disease management team. But all of my psychiatrists and psychologists are embedded in the Breast Center, and in the GI group, hepato-pancreato-biliary groups, and hepato-neck, and thoracic, and all that. So we're all interacting there. DANIEL HAYES: How do you translate that outside of Memorial in New York? I mean, most oncologists don't have access to those kinds of resources. And you've got to have thought about that. WILLIAM BREITBART: About 1996, the National Cancer Center Network, the NCCN, got established and started developing guidelines. And so they asked Jimmie to head up of their guidelines for distress. And I was part of that group, and still am. And what came out of that was screening for distress, using a distress screening tool. DANIEL HAYES: The distress thermometer-- the distress thermometer. WILLIAM BREITBART: The distress thermometer, that's exactly right. And that came out of the pain work. The pain guys had the 0 to 10 scale. We didn't want to rip them off too badly. So we didn't want to do the 0 to 10 visual analog scale. So we had to come up with a different metaphor. So we called it "pain throughout." So the Distress Screening Commission on Cancer, I think, accredits cancer centers through either the Academy of Surgery-- Surgical Oncology or something like that. They mandated that for a cancer center to get accredited, you have to have a distress screening program. And if you have a distress screening program, then you have to have people who respond to these algorithms that get developed for people who they identify with high distress. So as a result of that one move, that one move of establishing distress stress as the sixth vital sign, which was Jimmie's idea, and developing distress screening, you now have-- every designated NCI-designated cancer center has to have a psychology program of some sort. Now, a lot of them aren't as big as ours. Some of them basically involve a half-time psychiatrist, a chaplain, a psych nurse practitioner, and a couple of social workers. But every cancer center has psycho-oncology present in it now as a result of that. DANIEL HAYES: I was having dinner one time with Jim and Jimmie. And she said, you two know the blood pressure, the temperature, the weight, pulse. But you have no idea, she said, how they feel. So it wasn't the last time she asked Jim on that question. And I went, what do you mean? She goes, you need a distress thermometer. She'd already published it. Of course, I didn't know that-- and pulled it out of her purse. And so she had to show the distress thermometer. WILLIAM BREITBART: That's correct. That's correct. That's correct. One of the big problems is when Jimmie started-- and you can attest to this-- that in the beginnings of oncology, it wasn't always the case that patients were told exactly what they had. Cancer was very stigmatized. The only thing that's more stigmatized than an illness like cancer is mental health, right. God forbid, you should have a problem with depression, or coping, or panic, or something. DANIEL HAYES: It's a sign of weakness. WILLIAM BREITBART: A weakness, moral weakness. Actually, we've come a long way in terms of truth telling and being transparent. And my patients now know exactly all the genetic mutations of about the tumor and stuff like that. They know everything. And they even know how their tumor is-- mutations are evolving and changing over time. But cancer was-- the idea of needing psychosocial counseling-- psychiatric help, psychological help, it was very stigmatized. So even the word "distress" was chosen out of a concern to not stigmatize patients. DANIEL HAYES: I will tell you that when-- I was at the Dana Farber. And there was a push for the Dana Farber to develop its own hospice program. And Dr. Frye, who was physician-in-chief, absolutely drew a line, and said no way because that means we've given up on those patients. We're not going to have a hospice program at Dana Farber because we don't want patients to think they're coming here to die. And I remember thinking that some of them do. And it would be very helpful if we had a way to help them figure it out. And I have to say, in preparing for this podcast, I've read several your papers. And thought, God, I wish you'd been at the Dana Farber when I was there. Or I wish I'd been at Memorial to get to work with you. But you can see I'm kind of tying things up here. Because I could listen to you for hours,but But we only have 20 or 30 minutes. And this has been terrific. WILLIAM BREITBART: I appreciate the opportunity. DANIEL HAYES: I'm sure our listeners will say, maybe-- I wonder how we can get him to come speak to our program. But I already wrote down here, we're going to invite you to Michigan. WILLIAM BREITBART: Well, in this era of Zoom-- in this era of Zoom, I'm a very cheap date because all you have to do is just connect me by Zoom. You don't have to pay for the air fare or anything. I go everywhere. DANIEL HAYES: I want to thank you for lots of reasons. One is for filling our listeners in-- many of them are young-- about who Dr. Holland was and what she did. Because we all owe her an enormous debt of gratitude for the contributions she made-- and you personally, as well. So thank you for taking your time to speak with us. And we really appreciate it. And I hope our paths cross again in the near future. Thanks a lot. WILLIAM BREITBART: Absolutely. Thank you so much. It was my pleasure. Appreciate it. [MUSIC PLAYING] DANIEL HAYES: Until next time, thank you for listening to this JCO's Cancer Stories-- The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories-- The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]

No início dos anos 1980, diversos casos de uma doença infecciosa até então desconhecida começaram a surgir nos Estados Unidos. Os pacientes saudáveis eram diagnosticados com pneumonia, tuberculose e um tipo raro de câncer conhecido por sarcoma de Kaposi. Naquele momento, ninguém poderia imaginar estar testemunhando o início de um surto mundial que infectaria mais de 75 milhões de pessoas e mataria cerca de 35 milhões. Para falar sobre 40 anos do HIV e como o Brasil combateu a Aids, nosso convidado é o médico sanitarista, Gonzalo Vecina, que foi o primeiro diretor presidente da Anvisa.

No início dos anos 1980, diversos casos de uma doença infecciosa até então desconhecida começaram a surgir nos Estados Unidos. Os pacientes saudáveis eram diagnosticados com pneumonia, tuberculose e um tipo raro de câncer conhecido por sarcoma de Kaposi. Naquele momento, ninguém poderia imaginar estar testemunhando o início de um surto mundial que infectaria mais de 75 milhões de pessoas e mataria cerca de 35 milhões. Para falar sobre 40 anos do HIV e como o Brasil combateu a Aids, nosso convidado é o médico sanitarista, Gonzalo Vecina, que foi o primeiro diretor presidente da Anvisa.

Listen to this episode to know more about Kaposi's sarcoma. Do you want to know more about oral diseases? Follow us on Instagram @doencasdeboca https://www.instagram.com/doencasdeboca/

Did you ever suffer from a cold sore caused by the herpes virus? If so, this audio newsletter is for you. We go through all of the current data regarding cause and treatment. Herpes Labialis is a common recurrent irritation for many children and parents alike. The Red Book, the bible of pediatric Infectious diseases, is the best resource for understanding Herpes viral infections. There are 8 primary herpes viruses that infect humans including: herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, Human herpesvirus-6, Human herpesvirus-7, and Kaposi's sarcoma herpes virus...... Read More at https://www.salisburypediatrics.com/patient-education/dr-magryta-s-newsletter/955-volume-11-letter-24 Best, Dr. M  

** Thanks for downloading this episode. If you'd like to stay in touch with our continuing story, Season 2 continues at This Medical Life, in which Dr Travis Brown continues his exploration of diseases and our approaches to treatment from history to the modern day. Have a look in your podcast app now for This Medical Life, and hit subscribe so you never miss an episode ** In June 1981, the CDC reported an article of 5 men who presented with Pneumocystis pneumonia (PCP). PCP is an opportunistic infection more commonly found immunosuppressed patients (ie. patients receiving chemotherapy for cancer). The 5 men were young and otherwise healthy. They were also all homosexual. In July 1981, another CDC article reported 26 men who presented with PCP as well as Kaposi sarcoma. Kaposi sarcoma is a rare blood vessel tumour. This could not be a coincidence and the world was on the precipice of a pandemic that would kill millions and unleash a wave of homophobia, prejudice and demonization. Fortunately, today, HIV is a manageable disease and patients can continue to live productive and healthy lives which could not be further from this once terminal diagnosis. This is the story of HIV.See omnystudio.com/listener for privacy information.

In June 1981, the CDC reported an article of 5 men who presented with Pneumocystis pneumonia (PCP). PCP is an opportunistic infection more commonly found immunosuppressed patients (ie. patients receiving chemotherapy for cancer). The 5 men were young and otherwise healthy. They were also all homosexual. In July 1981, another CDC article reported 26 men who presented with PCP as well as Kaposi sarcoma. Kaposi sarcoma is a rare blood vessel tumour. This could not be a coincidence and the world was on the precipice of a pandemic that would kill millions and unleash a wave of homophobia, prejudice and demonization. Fortunately, today, HIV is a manageable disease and patients can continue to live productive and healthy lives which could not be further from this once terminal diagnosis. This is the story of HIV. See omnystudio.com/listener for privacy information.

REFERÊNCIAS1.Ko JP, Girvin F, Moore W, Naidich DP. Approach to Peribronchovascular Disease on CT. Semin Ultrasound CT MR. 2019;40(3):187-99.2.C. G. Pulmonary involvement in acquired immunodeficiency syndrome-associated Kaposi's sarcoma: a descriptive analysis of thin-section manifestations in 29 patients. Quant Imaging Med Surg. 2021;11(2):714-24.3.Restrepo CS, Ocazionez D. Kaposi's sarcoma: imaging overview. Semin Ultrasound CT MR. 2011;32(5):456-69.4.Gasparetto TD, Marchiori E, Lourenco S, Zanetti G, Vianna AD, Santos AA, et al. Pulmonary involvement in Kaposi sarcoma: correlation between imaging and pathology. Orphanet J Rare Dis. 2009;4:18.5.Chou SH, Prabhu SJ, Crothers K, Stern EJ, Godwin JD, Pipavath SN. Thoracic diseases associated with HIV infection in the era of antiretroviral therapy: clinical and imaging findings. Radiographics. 2014;34(4):895-911.6.Godoy MC, Rouse H, Brown JA, Phillips P, Forrest DM, Muller NL. Imaging features of pulmonary Kaposi sarcoma-associated immune reconstitution syndrome. AJR Am J Roentgenol. 2007;189(4):956-65.7.Bhatia K, Ellis S. Unusual lung tumours: an illustrated review of CT features suggestive of this diagnosis. Cancer Imaging. 2006;6:72-82.8.D. OM. Imaging Techniques for Kaposi Sarcoma (KS). J HIV Ther 2008;13(3):65-71.9.da Silva Filho FP, Marchiori E, Valiante PM, Escuissato DL, Gasparetto TD. AIDS-related Kaposi sarcoma of the lung presenting with a "crazy-paving" pattern on high-resolution CT: imaging and pathologic findings. J Thorac Imaging. 2008;23(2):135-7.

In 1959, the first case of immunodeficiency virus to infect a human was documented in Kinshasa, Democratic Republic of the Congo. Scientists would go on to theorize that the man contracted what became known as HIV-1 from a West African chimpanzee infected with simian immunodeficiency virus (SIV), probably from coming into contact with the chimp's blood while hunting and killing it for meat. Over the next couple of decades, the virus spread through Africa and to other parts of the world, including the United States by the late 1970s. That's when Kaposi sarcoma and Pneumocystis jiroveci pneumonia, rare illnesses that do not normally occur in people with healthy immune systems, began occurring in men who have sex with men (MSM) and intravenous (IV) drug users. In 1982, public health officials adopted the term acquired immunodeficiency syndrome, or AIDS, to describe these opportunistic infections. A year later, the virus that causes AIDS was discovered and named human T-cell lymphotropic virus-type III/lymphadenopathy-associated virus (HTLV-III/LAV). This unwieldy tongue-twister was later changed to human immunodeficiency virus (HIV). HIV is a retrovirus, which means that it converts its RNA into DNA for integration into a host genome. HIV interrupts the body's immune system. It is spread through blood and blood products, as well as through sexual contact, and can cause AIDS. After listening to this AudioBrick, you should be able to: Define HIV infection and AIDS, and discuss the epidemiology.1 Describe the replication and life cycle of a retrovirus, and describe how HIV infection leads to immune deficiency.2 Describe the presentation of a patient with HIV infection, with and without AIDS, and list common opportunistic infections seen in patients with AIDS.3 Describe the diagnosis of HIV and AIDS.4 Outline therapeutic and preventive approaches to HIV/AIDS. You can also check out the original brick from our Reproductive collection, which is available for free. Learn more about Rx Bricks by signing up for a free USMLE-Rx account: www.usmle-rx.com You will get 5 days of full access to our Rx360+ program, including nearly 800 Rx Bricks.  After the 5-day period, you will still be able to access over 150 free bricks, including the entire collections for General Microbiology and Cellular and Molecular Biology. *** If you enjoyed this episode, we'd love for you to leave a review on Apple Podcasts.  It helps with our visibility, and the more med students (or future med students) listen to the podcast, the more we can provide to the future physicians of the world. Follow USMLE-Rx at: Facebook: www.facebook.com/usmlerx Blog: www.firstaidteam.com Twitter: https://twitter.com/firstaidteam Instagram: https://www.instagram.com/firstaidteam/ YouTube: www.youtube.com/USMLERX Learn how you can access over 150 of our bricks for FREE: https://usmlerx.wpengine.com/free-bricks/

Here are the links for everything discussed in Episode 35, I'm also including times here so feel free to skip ahead to the topics that interest you. (1:19) Added indication for Pomalyst for Kaposi sarcoma (4:50) FDA approves Kynmobi for Parkinson's (8:57) Opdivo & Yervoy approval for mNSCLC w/ PD-L1 CDC updates on COVID-19 & influenza reporting Connect with The Rx Daily Dose:Twitter      Instagram      YouTube      Linkedin       WebsiteEmail: therxdailydose@gmail.comConnect with Ian Parnigoni PharmD. on social media:Twitter       Instagram       Linkedin  ★ Support this podcast on Patreon ★