From immunotherapy to mRNA vaccines – the latest science on melanoma treatment explained
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More than 16,000 Australians will be diagnosed with melanoma each year. Most of these will be caught early, and can be cured by surgery.
However, for patients with advanced or metastatic melanoma, which has spread from the skin to other organs, the outlook was bleak until the advent of targeted therapies (that attack specific cancer traits) and immune therapies (that leverage the immune system). Over the past decade, these treatments have seen a significant climb in the number of advanced melanoma patients surviving for at least five years after diagnosis, from less than 10% in 2011 to around 50% in 2021.
While this is great news, there are still many melanoma patients who cannot be treated effectively with current therapies. Researchers have developed two exciting new therapies that are being evaluated in clinical trials for advanced melanoma patients. Both involve the use of immunotherapy at different times and in different ways.
The first results from these trials are now being shared publicly, offering insight into the future of melanoma treatment.
Immunotherapy before surgery
Immunotherapy works by boosting the power of a patient’s immune system to help kill cancer cells. One type of immunotherapy uses something called “immune checkpoint inhibitors”.
Immune cells carry “immune checkpoint” proteins, which control their activity. Cancer cells can interact with these checkpoints to turn off immune cells and hide from the immune system. Immune checkpoint inhibitors block this interaction and help keep the immune system activated to fight the cancer.
Results from an ongoing phase 3 trial using immune checkpoint inhibitors were recently published in the New England Journal of Medicine.
This trial used two types of immune checkpoint inhibitors: nivolumab, which blocks an immune checkpoint called PD-1, and ipilimumab, which blocks CTLA-4.
Some 423 patients (including many from Australia) were enrolled in the trial, and participants were randomly assigned to one of two groups.
The first group had surgery to remove their melanoma, and were then given immunotherapy (nivolumab) to help kill any remaining cancer cells. Giving a systemic (whole body) therapy such as immunotherapy after surgery is a standard way of treating melanoma. The second group received immunotherapy first (nivolumab plus ipilimumab) and then underwent surgery. This is a new approach to treating these cancers.
Based on previous observations, the researchers had predicted that giving patients immunotherapy while the whole tumour was still present would activate the tumour-fighting abilities of the patient’s immune system much better than giving it once the tumour had been removed.
Sure enough, 12 months after starting therapy, 83.7% of patients who received immunotherapy before surgery remained cancer-free, compared to 57.2% in the control group who received immunotherapy after surgery.
Based on these results, Australian of the year Georgina Long – who co-led the trial with Christian Blank from The Netherlands Cancer Institute – has suggested this method of immunotherapy before surgery should be considered a new standard of treatment for higher risk stage 3 melanoma. She also said a similar strategy should be evaluated for other cancers.
The promising results of this phase 3 trial suggest we might see this combination treatment being used in Australian hospitals within the next few years.
mRNA vaccines
Another emerging form of melanoma therapy is the post-surgery combination of a different checkpoint inhibitor (pembrolizumab, which blocks PD-1), with a messenger RNA vaccine (mRNA-4157).
While checkpoint inhibitors like pembrolizumab have been around for more than a decade, mRNA vaccines like mRNA-4157 are a newer phenomenon. You might be familiar with mRNA vaccines though, as the biotechnology companies Pfizer-BioNTech and Moderna released COVID vaccines based on mRNA technology.
mRNA-4157 works basically the same way – the mRNA is injected into the patient and produces antigens, which are small proteins that train the body’s immune system to attack a disease (in this case, cancer, and for COVID, the virus).
However, mRNA-4157 is unique – literally. It’s a type of personalised medicine, where the mRNA is created specifically to match a patient’s cancer. First, the patient’s tumour is genetically sequenced to figure out what antigens will best help the immune system to recognise their cancer. Then a patient-specific version of mRNA-4157 is created that produces those antigens.
The latest results of a three-year, phase 2 clinical trial which combined pembrolizumab and mRNA-4157 were announced this past week. Overall, 2.5 years after starting the trial, 74.8% of patients treated with immunotherapy combined with mRNA-4157 post-surgery remained cancer-free, compared to 55.6% of those treated with immunotherapy alone. These were patients who were suffering from high-risk, late-stage forms of melanoma, who generally have poor outcomes.
It’s worth noting these results have not yet been published in peer-reviewed journals. They’re available as company announcements, and were also presented at some cancer conferences in the United States.
Based on the results of this trial, the combination of pembrolizumab and the vaccine progressed to a phase 3 trial in 2023, with the first patients being enrolled in Australia. But the final results of this trial are not expected until 2029.
It is hoped this mRNA-based anti-cancer vaccine will blaze a trail for vaccines targeting other types of cancer, not just melanoma, particularly in combination with checkpoint inhibitors to help stimulate the immune system.
Despite these ongoing advances in melanoma treatment, the best way to fight cancer is still prevention which, in the case of melanoma, means protecting yourself from UV exposure wherever possible.
Sarah Diepstraten, Senior Research Officer, Blood Cells and Blood Cancer Division, WEHI (Walter and Eliza Hall Institute of Medical Research) and John (Eddie) La Marca, Senior Research Officer, Blood Cells and Blood Cancer, WEHI (Walter and Eliza Hall Institute of Medical Research)
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Fennel vs Artichoke – Which is Healthier?
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Our Verdict
When comparing fennel to artichoke, we picked the artichoke.
Why?
Both are great! But artichoke wins on nutritional density.
In terms of macros, artichoke has more protein and more fiber, for only slightly more carbs.
Vitamins are another win for artichoke, boasting more of vitamins B1, B2, B3, B5, B6, B9, and choline. Meanwhile, fennel has more of vitamins A, E, and K, which is also very respectable but does allow artichoke a 6:3 lead.
In the category of minerals, artichoke has a lot more copper, iron, magnesium, manganese, and phosphorus, while fennel has a little more calcium, potassium, and selenium.
One other relevant factor is that fennel is a moderate appetite suppressant, which may be good or bad depending on your food-related goals.
All in all though, we say the artichoke wins by virtue of its greater abundance of nutrients!
Want to learn more?
You might like to read:
What Matters Most For Your Heart? ← appropriately enough, with fennel hearts and artichoke hearts!
Take care!
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Statistical Models vs. Front-Line Workers: Who Knows Best How to Spend Opioid Settlement Cash?
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MOBILE, Ala. — In this Gulf Coast city, addiction medicine doctor Stephen Loyd announced at a January event what he called “a game-changer” for state and local governments spending billions of dollars in opioid settlement funds.
The money, which comes from companies accused of aggressively marketing and distributing prescription painkillers, is meant to tackle the addiction crisis.
But “how do you know that the money you’re spending is going to get you the result that you need?” asked Loyd, who was once hooked on prescription opioids himself and has become a nationally known figure since Michael Keaton played a character partially based on him in the Hulu series “Dopesick.”
Loyd provided an answer: Use statistical modeling and artificial intelligence to simulate the opioid crisis, predict which programs will save the most lives, and help local officials decide the best use of settlement dollars.
Loyd serves as the unpaid co-chair of the Helios Alliance, a group that hosted the event and is seeking $1.5 million to create such a simulation for Alabama.
The state is set to receive more than $500 million from opioid settlements over nearly two decades. It announced $8.5 million in grants to various community groups in early February.
Loyd’s audience that gray January morning included big players in Mobile, many of whom have known one another since their school days: the speaker pro tempore of Alabama’s legislature, representatives from the city and the local sheriff’s office, leaders from the nearby Poarch Band of Creek Indians, and dozens of addiction treatment providers and advocates for preventing youth addiction.
Many of them were excited by the proposal, saying this type of data and statistics-driven approach could reduce personal and political biases and ensure settlement dollars are directed efficiently over the next decade.
But some advocates and treatment providers say they don’t need a simulation to tell them where the needs are. They see it daily, when they try — and often fail — to get people medications, housing, and other basic services. They worry allocating $1.5 million for Helios prioritizes Big Tech promises for future success while shortchanging the urgent needs of people on the front lines today.
“Data does not save lives. Numbers on a computer do not save lives,” said Lisa Teggart, who is in recovery and runs two sober living homes in Mobile. “I’m a person in the trenches,” she said after attending the Helios event. “We don’t have a clean-needle program. We don’t have enough treatment. … And it’s like, when is the money going to get to them?”
The debate over whether to invest in technology or boots on the ground is likely to reverberate widely, as the Helios Alliance is in discussions to build similar models for other states, including West Virginia and Tennessee, where Loyd lives and leads the Opioid Abatement Council.
New Predictive Promise?
The Helios Alliance comprises nine nonprofit and for-profit organizations, with missions ranging from addiction treatment and mathematical modeling to artificial intelligence and marketing. As of mid-February, the alliance had received $750,000 to build its model for Alabama.
The largest chunk — $500,000 — came from the Poarch Band of Creek Indians, whose tribal council voted unanimously to spend most of its opioid settlement dollars to date on the Helios initiative. A state agency chipped in an additional $250,000. Ten Alabama cities and some private foundations are considering investing as well.
Stephen McNair, director of external affairs for Mobile, said the city has an obligation to use its settlement funds “in a way that is going to do the most good.” He hopes Helios will indicate how to do that, “instead of simply guessing.”
Rayford Etherton, a former attorney and consultant from Mobile who created the Helios Alliance, said he is confident his team can “predict the likely success or failure of programs before a dollar is spent.”
The Helios website features a similarly bold tagline: “Going Beyond Results to Predict Them.”
To do this, the alliance uses system dynamics, a mathematical modeling technique developed at the Massachusetts Institute of Technology in the 1950s. The Helios model takes in local and national data about addiction services and the drug supply. Then it simulates the effects different policies or spending decisions can have on overdose deaths and addiction rates. New data can be added regularly and new simulations run anytime. The alliance uses that information to produce reports and recommendations.
Etherton said it can help officials compare the impact of various approaches and identify unintended consequences. For example, would it save more lives to invest in housing or treatment? Will increasing police seizures of fentanyl decrease the number of people using it or will people switch to different substances?
And yet, Etherton cautioned, the model is “not a crystal ball.” Data is often incomplete, and the real world can throw curveballs.
Another limitation is that while Helios can suggest general strategies that might be most fruitful, it typically can’t predict, for instance, which of two rehab centers will be more effective. That decision would ultimately come down to individuals in charge of awarding contracts.
Mathematical Models vs. On-the-Ground Experts
To some people, what Helios is proposing sounds similar to a cheaper approach that 39 states — including Alabama — already have in place: opioid settlement councils that provide insights on how to best use the money. These are groups of people with expertise ranging from addiction medicine and law enforcement to social services and personal experience using drugs.
Even in places without formal councils, treatment providers and recovery advocates say they can perform a similar function. Half a dozen advocates in Mobile told KFF Health News the city’s top need is low-cost housing for people who want to stop using drugs.
“I wonder how much the results” from the Helios model “are going to look like what people on the ground doing this work have been saying for years,” said Chance Shaw, director of prevention for AIDS Alabama South and a person in recovery from opioid use disorder.
But Loyd, the co-chair of the Helios board, sees the simulation platform as augmenting the work of opioid settlement councils, like the one he leads in Tennessee.
Members of his council have been trying to decide how much money to invest in prevention efforts versus treatment, “but we just kind of look at it, and we guessed,” he said — the way it’s been done for decades. “I want to know specifically where to put the money and what I can expect from outcomes.”
Jagpreet Chhatwal, an expert in mathematical modeling who directs the Institute for Technology Assessment at Massachusetts General Hospital, said models can reduce the risk of individual biases and blind spots shaping decisions.
If the inputs and assumptions used to build the model are transparent, there’s an opportunity to instill greater trust in the distribution of this money, said Chhatwal, who is not affiliated with Helios. Yet if the model is proprietary — as Helios’ marketing materials suggest its product will be — that could erode public trust, he said.
Etherton, of the Helios Alliance, told KFF Health News, “Everything we do will be available publicly for anyone who wants to look at it.”
Urgent Needs vs. Long-Term Goals
Helios’ pitch sounds simple: a small upfront cost to ensure sound future decision-making. “Spend 5% so you get the biggest impact with the other 95%,” Etherton said.
To some people working in treatment and recovery, however, the upfront cost represents not just dollars, but opportunities lost for immediate help, be it someone who couldn’t find an open bed or get a ride to the pharmacy.
“The urgency of being able to address those individual needs is vital,” said Pamela Sagness, executive director of the North Dakota Behavioral Health Division.
Her department recently awarded $7 million in opioid settlement funds to programs that provide mental health and addiction treatment, housing, and syringe service programs because that’s what residents have been demanding, she said. An additional $52 million in grant requests — including an application from the Helios Alliance — went unfunded.
Back in Mobile, advocates say they see the need for investment in direct services daily. More than 1,000 people visit the office of the nonprofit People Engaged in Recovery each month for recovery meetings, social events, and help connecting to social services. Yet the facility can’t afford to stock naloxone, a medication that can rapidly reverse overdoses.
At the two recovery homes that Mobile resident Teggart runs, people can live in a drug-free space at a low cost. She manages 18 beds but said there’s enough demand to fill 100.
Hannah Seale felt lucky to land one of those spots after leaving Mobile County jail last November.
“All I had with me was one bag of clothes and some laundry detergent and one pair of shoes,” Seale said.
Since arriving, she’s gotten her driver’s license, applied for food stamps, and attended intensive treatment. In late January, she was working two jobs and reconnecting with her 4- and 7-year-old daughters.
After 17 years of drug use, the recovery home “is the one that’s worked for me,” she said.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
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Beetroot vs Sweet Potato – Which is Healthier?
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Our Verdict
When comparing beetroot to sweet potato, we picked the sweet potato.
Why?
Quite a straightforward one today!
In terms of macros, sweet potato has more protein, carbs, and fiber. The glycemic index of both of these root vegetables is similar (and in each case varies similarly depending on how it is cooked), so we’ll call the winner the one that’s more nutritionally dense—the sweet potato.
Looking at vitamins next, beetroot has more vitamin B9 (and is in fact a very good source of that, unlike sweet potato), and/but sweet potato is a lot higher in vitamins A, B1, B2, B3, B5, B6, B7, C, E, K, and choline. And we’re talking for example more than 582x more vitamin A, more than 17x more vitamin E, more than a 10x more vitamin K, and at least multiples more of the other vitamins mentioned. So this category’s not a difficult one to call for sweet potato.
When it comes to minerals, beetroot has more selenium, while sweet potato has more calcium, copper, magnesium, manganese, phosphorus, and potassium. They’re approximately equal in iron and zinc. Another win for sweet potato.
Of course, enjoy both. But if you’re looking for the root vegetable that’ll bring the most nutrients, it’s the sweet potato.
Want to learn more?
You might like to read:
No, beetroot isn’t vegetable Viagra. But here’s what else it can do
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Get Better Sleep: Beyond “Sleep Hygiene”
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Better Sleep, Better Life!
This is Arianna Huffington. Yes, that Huffington, of the Huffington Post. But! She’s also the CEO of Thrive Global, a behavior change tech company with the mission of changing the way we work and live—in particular, by challenging the idea that burnout is the required price of success.
The power of better sleep
Sleep is a very important, but most often neglected, part of good health. Here are some of Huffington’s top insights from her tech company Thrive, and as per her “Sleep Revolution” initiative.
Follow your circadian rhythm
Are you a night owl or a morning lark? Whichever it is, roll with it, and plan around that if your lifestyle allows for such. While it is possible to change from one to the other, we do have a predisposition towards one or the other, and will generally function best when not fighting it.
This came about, by the way, because we evolved to have half of us awake in the mornings and half in the evenings, to keep us all safe. Socially we’ve marched onwards from that point in evolutionary history, but our bodies are about a hundred generations behind the times, and that’s just what we have to work with!
Don’t be afraid (or ashamed!) to take naps
Naps, done right, can be very good for the health—especially if we had a bad night’s sleep the previous night.
Thrive found that workers are more productive when they have nap rooms, and (following on a little from the previous point) are allowed to sleep in or work from home.
See also: How To Nap Like A Pro (No More “Sleep Hangovers”!)
Make sure you have personal space available in bed
The correlation between relationship satisfaction and sleeping close to one’s partner has been found to be so high that it’s even proportional: the further away a couple sleeps from each other, the less happy they are. But…
Partners who got good sleep the previous night, will be more likely to want intimacy on any given night—at a rate of an extra 14% per extra hour of sleep the previous night. So, there’s a trade-off, as having more room in bed tends to result in better sleep. Time to get a bigger bed?
What gets measured, gets done
This goes for sleep, too! Not only does dream-journaling in the morning cue your subconscious to prepare to dream well the following night, but also, sleep trackers and sleep monitoring apps go a very long way to improving sleep quality, even if no extra steps are consciously taken to “score better”.
We’ve previously reviewed some of the most popular sleep apps; you can check out for yourself how they measured up:
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Hanging Exercises For Complete Beginners & Older Adults
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Hanging (not the kind with a gallows) is great for the heath, improving not just strength and mobility, but also—critically—looking after spinal health too. Amanda Raynor explains in this video how this exercise is accessible to anyone (unless you have no arms, in which case, sorry, this one is just not for you—though hanging by your legs will also give similar spinal benefits!).
Hanging out
Hanging can be done at home or at a park, with minimal equipment (a bar, a sturdy tree branch, etc).
Note: the greater the diameter of the bar, the more it will work your grip strength, and/but the harder it will be. So, it’s recommend to start with a narrow-diameter bar first.
Getting started:
- Start with a “dead hang”: grip the bar with hands shoulder-width apart, thumb wrapped around.
- Aim to hang without pulling up; build endurance gradually (10–30 seconds is fine at first).
- Work up to holding for 60 seconds in three sets as a fitness goal.
Progression:
- If unable to hang at all initially, use a chair or stool to support some body weight.
- Gradually reduce foot support to increase duration of free hanging.
- Start with 10 seconds, progressing by small increments (e.g: 15, 20, 25 seconds) until reaching 60 seconds.
Advanced variations:
- Move the body while hanging (e.g., circles, knee lifts).
- Experiment with different grips (overhand, underhand) for varied muscle engagement.
- Try scapular pulls or one-arm hangs for additional challenge and strength-building.
For more on all of this plus visual demonstrations, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
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Barley Malt Flour vs chickpea flour – Which is Healthier?
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Our Verdict
When comparing barley malt flour to chickpea flour, we picked the chickpea.
Why?
First, some notes:
About chickpea flour: this is also called besan flour, gram flour, and garbanzo bean flour; they are all literally the same thing by different names, and are all flour made from ground chickpeas.
About barley malt flour: barley is a true grain, and does contain gluten. We’re not going to factor that into today’s decision, but if you are avoiding gluten, avoid barley. As for “malt”; malting grains means putting them in an environment (with appropriate temperature and humidity) that they can begin germination, and then drying them with hot air to stop the germination process from continuing, so that we still have grains to make flour out of, and not little green sprouting plants. It improves the nutritional qualities and, subjectively, the flavor.
To avoid repetition, we’re just going to write “barley” instead of “barley malt” now, but it’s still malted.
Now, let’s begin:
Looking at the macros first, chickpea flour has 2x the protein and also more fiber, while barley flour has more carbs. An easy win for chickpea flour.
In the category of vitamins, chickpea flour has more of vitamins A, B1, B5, B9, E, and K, while barley flour has more of vitamins B2, B3, B6, and C. A modest 6:4 victory for chickpea flour.
When it comes to minerals, things are much more one-sided; chickpea flour has more calcium, copper, iron, magnesium, manganese, phosphorus, potassium, and zinc, while barley flour has more selenium. An overwhelming win for chickpea flour.
Adding up these three wins for chickpea flour makes for a convincing story in favor of using that where reasonably possible as a flour! It has a slight nutty taste, so you might not want to use it in everything, but it is good for a lot of things.
Want to learn more?
You might like to read:
- Grains: Bread Of Life, Or Cereal Killer?
- Gluten: What’s The Truth?
- Sprout Your Seeds, Grains, Beans, Etc
Take care!
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