Category Archives: Alternative Medicine

When it comes to medicine, everybody seems to have an opinion. Regardless of background, status, or financial situation, everybody has to worry about their health, so the shared interest makes a lot of sense. With so much information out there, it can be easy to get lost in the chaos, particularly debates around conventional and alternative medicines.

What is alternative medicine, anyway? It depends on who you ask, but when you boil it down, its just any sort of treatment you wouldnt normally expect to undergo in your family doctors office. It might be an herbal supplement thats still being studied or just an option thats not practiced a whole lot in some parts of the world. While complementary medicine refers to something done in addition to traditional treatment, alternate medicine is done instead of the conventional method. Regardless, people can get pretty emotional when you challenge their medical claims. Always speak to your medical provider before trying any alternative medicine regimen. Without further ado, here are ten alternative medicines people swear by.

Related: Top 10 Bizarre Things Doctors Prescribe Instead of Medicine

Aromatherapy: How Essential are Essential Oils?

Ah, can you smell the healing? Youd be hard-pressed these days to find somebody who has never heard of essential oils or aromatherapy. According to the National Institute of Health, aromatherapy is a type of alternative medicine that uses plant oils to promote healing, stress relief, and a sense of well-being.

So, does it work? Well, again, it seems to depend on who you ask, but there does seem to be research confirming the effectiveness of essential oils when it comes to treating specific mild ailments like stress or trouble falling asleep.

Aromatherapy can involve a long list of essential oils, from the pleasantly-scented peppermint oil to oregano oil, which can supposedly help with digestion.

Topical Capsaicin (Active Ingredient in Peppers) to Treat Joint Pain

You might know an elderly member in your family who struggles with arthritis or joint pain. Maybe you personally experience aches and pains in your joints and wonder if there are any dietary changes you might be able to make to help yourself feel better. As it turns out, maybe you can!

The key is a substance called capsaicin. It is found not only in ghost peppers but in all chili peppers, so if you need a milder solution, you could just pour yourself a nice big bowl of jalapenos or perhaps add a little hot sauce to your morning oatmeal (Okay, please dont do that last one). Capsaicin seems to have the benefit of relieving joint pain due to the bodys reaction to the substance when used as a topical solution, so just eating a bunch of these peppers might not actually be effective, but the research is in the works. It seems to work by a unique interaction with pain receptors, or maybe if you eat enough of them, your mouth will be so on fire that you just wont notice the joint pain anymore.

In any case, some people swear by the health benefits of chili peppers, often crediting it with pain relief. I suppose if you like spicy food, it wont hurt much to give this alternate medicine a go, even if it lands you spending a little extra time in the bathroom.

The Truth About Green Tea extract

The weight-loss industry is a multi-billion dollar market. There could be a variety of reasons for this, from the fact that people decide to prioritize their health but then want to take shortcuts to the fact that a lot of supplements and routines on the market dont necessarily do what they say theyre going to do.

In any case, while there are plenty of ridiculous diet fads out there, there does seem to be some promising information and research on the effect of green tea extract on the body, at least in combination with a good diet and moderate exercise. Which does sort of put it in the complementary category, but enough people swear by it that it made the list. Does it burn fat? Maybe. Even if youre not looking to burn fat, many claim green tea extract also helps with gut inflammation, which could potentially give the appearance of burning fat.

The claims about green tea go beyond mere fat burning, with some people making some pretty miraculous claims about its ability to help with an upset stomach, sore throat, and quicker healing. Some people have questioned the amount of green tea extract you ought to have before its dangerous. I wouldnt necessarily recommend taking the whole bottle, and it does have caffeine, so be careful if you decide to test this one yourself.

Chelation Therapy with Dr Steve Windley

Chelation therapy used to be considered a traditional medicinal treatment process. However, there is also a sort of alternative approach with a different view of toxins. The idea behind chelation therapy is that the body deals with pollutants that need to be removed. Traditionally, chelation therapy was used to pull out (as chelation means) toxins in the body, such as to treat a child who has swallowed lead. The idea that people might use this preventatively is whats controversial.

The Science Behind How Acupuncture Helps Relieve Pain: A Doctor Of Chinese Medicine Explains

Though acupuncture is a perfectly acceptable, traditional medicine in Eastern cultures and has been around for a long time, it is still not a well-known mainstream treatment in the West. Chinese practitioners say the human body has more than 2,000 acupuncture points connected throughout the body via the bloodstream. The practice of acupuncture in Chinese medicine aims to allow something called the Qi to flow more efficiently throughout the body.

The idea behind why and how acupuncture works seems a bit more philosophical than logical to our Western-trained ear. Still, it has certainly become more prevalent in places like the United States, as there are plenty of specialized centers you can go to for that type of treatment.

It seems to have gained popularity in recent years, particularly for athletes who need to recover after a hard day at the gym. According to a Fox News report, it has been popular among celebrities for quite a while but was reportedly growing in popularity among everyday Americans in recent years, increasing by approximately 6 million users between 2002 and 2007. One reason for the increase in popularity and availability today might be that, even if there continues to be debate over its efficacy, it is a relatively safe treatment, having very few side effects.

5 Brilliant Benefits of Ashwagandha

If youve never heard of Ashwagandha or knew how to spell it, here you are: a brand new medicine people swear by. Okay, so its not exactly new, but its use is trending.

Ashwagandha, also called the winter cherry, is a fruit from an evergreen shrub growing in India, the Middle East, and Africa. The claims about this plant are no small feat for a little shrub, ranging from better sleep to a regulated heart rate. The idea is that it works by reducing inflammation, so it might even be a promising solution for healing from infection.

You can pick it up in capsule form, gummy form, or even mixed in a mushroom-based tea in the western world, all likely available at your local supermarket. Watch the video to learn how to take it properly and in the most cost-effective dose.

How CBD Oil Impacts the Body

Thought you could make it through an article on alternate medicine without encountering CBD oil? You thought wrong. The fact is, CBD products have gained popularity in recent years, with the rise of attention to medical marijuana. To be clear, this is not the same thing; CBD oil does not have the same components as medical marijuana. It can be taken as a pill or as a topical medicine.

As for the actual benefits of CBD, it is hard to say. It is still under scrutiny by medical researchers at institutions like Harvard to determine how it compares to traditional medicine. Still, the benefits do seem to include pain relief, better sleep, decreased anxiety, and possibly even better results with addiction treatment from other substances. Listen to a podcast or two for long enough, and youll realize how popular this particular remedy is. As medical marijuana and CBD products gain more popularity across the country, perhaps their use will become more widespread as we learn more.

Alternative Medicine for ED | Erection Problems

The category of alternate male enhancement treatments, including herbal supplements, can be a little embarrassing to talk about. Maybe thats why so many guys search for natural remedies rather than talking to their doctor about these personal problems. However, erectile dysfunction, or ED, is an incredibly common problem and nothing to be ashamed of. According to this Verywell health article, the condition affects approximately 30 million men in the U.S.

As with any other medical usage, you should ask your doctor before simply deciding to treat yourself naturally. Why? While many consider natural treatments and herbal products safer, that is not necessarily the case. Be aware of the scams out there just looking to take advantage of you, but hey, if you can treat the problem naturally and get back to a more fulfilling bedroom experience while saving some money on medication in the process, why not? In addition to these natural supplements, there is plenty of evidence that basic self-care can also help to decrease instances of ED.

You might have noticed a theme in this list: Almost every treatment solves problems related to stress, whether directly or indirectly. Hydrotherapy is yet another example, which appears to decrease cortisol.

Hydrotherapy can involve hot or cold water to promote healing. Water takes your body weight off your skeleton, so water exercises can be a great way to work out without putting excess pressure on your bones and joints. Although hydrotherapy has been around for centuries, it has evolved with the healthcare industry introducing new hydrotherapy-promoting products all the time, like the Jacuzzi solution.

The good thing is, you can do some hydrotherapy on your own without going to any special clinic. For example, an ice bath after a workout is one form of hydrotherapy.

Hyperbaric Oxygen Therapy: Mayo Clinic Radio

Hyperbaric Oxygen Treatment (HBOT) involves the treatment of tissue damage by helping the body take in a greater amount of oxygen. The air that we normally inhale is about 20% oxygen. Inside something called a hyperbaric chamber, a patient takes in 100% pure oxygen.

This treatment is currently limited to about ten to fifteen conditions, depending on who is speaking. This treatment has been studied and verified to show statistically superior results over those patients who did not receive hyperbaric treatment.

The treatment seems to work well for athletes recovering from a lot of strain on the body or those with physically demanding jobs who need faster healing.

fact checked by Rachel Jones

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10 Alternate Medicines That People Swear By - nation.lk - The Nation Newspaper

Pain is one of the most commonly reported symptoms of arthritis. Several over-the-counter and prescription medicines can help, as can self-care strategies and alternative treatments.

Chronic arthritis pain affects 1 in 4 people in the United States. This pain can be severe and located in the joints.

Several medicines can manage arthritis pain. The best treatment depends on various factors, including:

This article explores the best approaches to arthritis pain and other symptoms, including medications, home remedies, lifestyle changes, and alternative treatments.

Some of the medications we discuss can cause an allergic reaction, which can be severe.

For someone with arthritis, pain and stiffness in the joints can make moving difficult. Medicines aim to manage pain, prevent joint damage, and maintain or improve mobility.

These drugs may be available over-the-counter (OTC) or by prescription. Most of the medications are oral, but people can apply or inject others to the skin.

A person can buy these at grocery stores and pharmacies without a prescription. These are generally safe, but having certain health conditions or taking other medications can make them less safe.

Acetaminophen (Tylenol) treats fevers and mild-to-moderate pain.

It works by reducing the production of prostaglandins, compounds made from fats that can increase sensitivity to pain.

A person may be choosing between Tylenol and a nonsteroidal anti-inflammatory drug (NSAID) such as Motrin or Advil. Arthritis usually causes inflammation in the joints, and NSAIDs combat inflammation, while acetaminophen does not.

For adults, doctors warn against taking more than 4 grams of acetaminophen per day to prevent an overdose. Many medicines contain acetaminophen, so is crucial to check all drug labels carefully and stay below this limit.

Acetaminophen is safe for pregnant people and children, but during pregnancy, take the lowest effective dose for the shortest necessary amount of time. This is to prevent rare but serious complications.

This drug can also cause serious adverse effects, including:

Anyone experiencing shortness of breath or nausea and vomiting needs urgent medical attention.

NSAIDs are considered one of the most effective OTC drugs for pain stemming from osteoarthritis, which causes inflammation. These drugs reduce pain, stiffness, and swelling from arthritis.

A common examples of NSAIDs include ibuprofen (Advil, Motrin).

Side effects can include:

NSAIDs also put a person at a higher risk of stroke, heart attack, and renal damage.

A person should only use these drugs when needed. If this is on a daily basis, doctors prescribe proton pump inhibitors or H2 blockers to prevent gastrointestinal problems stemming from NSAID use.

To avoid complications, people who are pregnant, breastfeeding, or over 65, or who have other ongoing health conditions, should speak with a healthcare professional before taking these medications.

Non-prescription aspirin can treat mild to moderate pain. It is a unique type of NSAID because it prevents the formation of blood clots.

Taking ibuprofen within several hours after taking aspirin may interfere with aspirins cardiovascular benefits, and it can increase the risk of side effects.

Read more about possible side effects of mixing these NSAIDs.

Medicated creams, gels, liquids or patches may help people when arthritis only affects the small joints, such as those in the fingers.

These products may contain NSAIDs, capsaicin, an anesthetic called lidocaine, menthol, camphor, or a combination.

Topical NSAIDs may work for people who cannot take these drugs orally because the body absorbs less through the skin. Doctors consider topical NSAIDs to be safer in the management of arthritis.

Read more about precautions to take with oral NSAIDs.

For some people, treating arthritis also requires medications that a doctor prescribes.

These are more potent than those available OTC. Examples of prescription NSAIDs are:

Doctors only prescribe opioids when other, safer pain relievers do not work. These drugs can help ease persistent, moderate-to-severe pain otherwise limits the quality of life. It is crucial to take the lowest effective dosage for the shortest effective period of time.

Examples of opioid medications include oxycodone, codeine, and tramadol.

Opioids can have serious risks, including overdose and addiction, and they are not appropriate for everyone. An overdose can be fatal, and long-term use can increase the risk of addiction and withdrawal. The doctor will describe the risks, possible benefits, and alternatives.

Opioids may also cause side effects, including:

Working with the doctor to establish goals and guidelines for safe use is key. An opioid pain agreement consent form may be a good idea before the treatment begins.

Steroids reduce the activity of the immune system to lower inflammation.

They are fast-acting, which makes them useful as an initial treatment before other medications take effect. It is important to note that steroids do not treat all causes of pain, only inflammatory disorders.

Doctors prescribe steroids as oral or injected medications. Steroid injections can cause infections, bleeding, skin discoloration, an allergic reaction, and tendon damage.

Corticosteroids are best for short-term use, if possible, because they can have a number of side effects.

Long-term use of any steroids can cause:

Glucocorticoids are a type of corticosteroids, and they can cause avascular bone necrosis. They can also play a role in the development non-alcohol-related fatty liver disease.

Hyaluronan, or hyaluronic acid, is a fluid that cushions and lubricates the joints. Doctors can inject it to treat osteoarthritis in the knee.

Studies, such as research from 2015, have concluded that hyaluronic acid can help manage this condition by reducing pain and improving joint function. However, the effects may only be moderate and short term.

Doctors may prescribe antidepressants to manage chronic pain due to osteoarthritis.

Antidepressants can cause side effects, including:

Read more about side effects of antidepressants.

The following approaches may help reduce the symptoms of arthritis:

Regular physical activity may reduce joint stiffness and pain and improve mobility for people with arthritis. A person might try low-impact exercises, such as:

According to the Arthritis Foundation, some vitamins and supplements can help with arthritis symptoms.

Although studies have found mixed results, glucosamine and chondroitin may relieve joint pain and help maintain cartilage structure.

Another option is curcumin. This is the active ingredient in turmeric. Its anti-inflammatory properties mimic the effects of ibuprofen, but without the side effects.

Read more about the best supplements for arthritis here.

Having extra weight can place added stress on weight-bearing joints, such as the knees and hips.

For some people who are overweight, losing 1 pound (lb) can relieve 4 lb of pressure on the knees. This can reduce pain and help improve function and mobility.

Cold compresses can soothe painful, swollen joints. And adding heat therapy to a morning routine can help loosen the joints and reduce muscle spasms and stiffness.

Crutches, a cane, or a walker can help relieve pressure on the joints, preventing overuse and promoting healing. These can also help improve balance and prevent falls for people with arthritis.

Using dressing aids, grabbers, and other long-handled equipment can reduce straining and help people with limited mobility.

Learn more about the best home remedies for arthritis here.

Several promising alternative treatments are available for people with arthritis. But limited studies support their effectiveness.

Read more about fish oil for arthritis.

While arthritis has no cure, a range of medications and self-care strategies can help manage symptoms and reduce the likelihood of flare-ups.

Treating arthritis involves managing pain, maintaining or improving function and mobility, and delaying joint damage. The best approach involves a mix of medications and alternative therapies, including self-care strategies.

A healthcare professional will consider the severity of arthritis and a range of factors specific to each person before they recommend a course of action.

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What is the best medicine for arthritis pain? - Medical News Today

The Good Clinic opened its doors this December on the cross street of Snelling and St. Clair avenues under the Grove Apartments. This family health clinic claims to redefine health care and create a unique boutique environment for its clients.

The clinic has five other locations throughout the greater Minneapolis area, but this is the first branch in St. Paul. In choosing this new location, Good Clinic CEO Michael Howe said that he thought the Macalester-Groveland Neighborhood lacks the amount of primary care that its population needs.

In this part of St. Paul with young professional families immediately around it there really arent many primary care practices that they can access, Howe said. We felt that this would be a service to the community

Howe has a history in the business of health care, most notably as CEO of Minute Clinic, a walk-in health care service which CVS in 2006. To serve Macalesters student population, Howe said that The Good Clinic offers a range of primary healthcare services such as treatment for the flu, infections, allergies, STIs and sprains. They also have typical preventative care such as physical exams, and immunizations for flu and COVID-19. However, what they say sets them apart from family practitioners is the way they created their business.

We built our concepts based on expertise, empathy and education, Howe said.

The Good Clinic claims to be a family practitioner 3.0 in the way they interact with patients and create a welcoming environment. They call their patients clients. They also named their waiting room the welcome area and filled it with natural light and modern furniture.

The Good Clinic mixes traditional family practitioners with alternative medicine such as their use of supplements to aid in healthcare. Howe said that the clinics aim is to create a positive environment for the patient that is less transactional and more focused on meaningful connections.

The Good Clinic also claims to promote long-term health, something that Howe believed was not typically on college students minds. They are particularly proud of their wellness planning where they emphasize the interconnectedness of all aspects of health and offer counseling visits to curate a plan to improve your health. The services include biometric screening, depression and anxiety management, behavioral health evaluations and exercise and weight management counseling.

The Good Clinic claims to look beyond primary care and into more holistic and modern applications of primary care. Does this level of care come with a higher price tag? Howe says no.

The investments were making to establish the relations with each of our clients is the time and effort to help educate them on how to get the most out of a health care system, Howe said.

The Good Clinic is in the network for typical insurances such as Medicare, BlueCross BlueShield Minnesota, Humana and Medica. They also accept Macalester health insurance under UnitedHealthcare. Howe says that all their extra features will not cost the patient any more than a typical family practitioner.

The Good Clinic has also partnered with the National Minority Health Association (NMHA) to address and solve health equality problems. NMHA is working on a grant to increase services and outreach to communities in need. According to Howe, the Good Clinic would put this grant into practice and provide this service and outreach. The grant is in the early stages, but its goals are vast in attempts to increase access to health care in Minnesota.

Howe said that The Good Clinic offers a comfortable, welcoming and calming environment and an alternative to typical healthcare. He emphasized their accessibility both online and in-person through same and next-day appointments.

Howe believes college students often dont prioritize their wellness and said that could be harmful and expressed that The Good Clinic could fill health needs that arent met on campus.

Part of our approach to care is that we value sick care but also wellness care, Howe said as college students, I think back to myself, you think of yourself as invincible and dont think how to manage your health care.

Prioritizing health for college students may not be on everyones mind, but the Good Clinic attempts to offer convenience and a unique experience. Howe expressed confidence in their business model. The clinic plans on having four more clinics in the area by the end of the year and even expanding to Denver.

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New clinic seeks to provide wellness and alternative health care - Macalester College The Mac Weekly

I wasnt so shocked as I was wary, because I knew what was ahead of me because the negative mind-body bias was so strong, he told Brainworld magazine in 2019. I remained a cardiologist and also being head of cardiovascular teaching at Harvard Medical School, but I sustained two professional lives. I kept respectability within cardiology while I also did work in the mind-body field.

Working with Robert Keith Wallace, a young physiologist at the University of California, Los Angeles, he published his first findings in the early 1970s. Press reports called him a renegade and a maverick, and many in his profession shunned him.

But others were impressed by the strength of his research, and by his objectivity. Unlike some researchers at the time, including Dr. Wallace, Dr. Benson was not an advocate of Transcendental Meditation; in fact, he split with Dr. Wallace when he insisted that there was nothing special about the practice or the use of mantras any word or phrase, repeated over and over, will do, he said.

Dr. Benson called his approach the relaxation response the opposite of the fight-or-flight response. But whereas a stressful situation will cause the body to automatically raise its heart rate and release adrenaline, the relaxation response has to be asserted consciously.

He demonstrated just how to do that in his book The Relaxation Response, published in 1975. It hit at the right time: That same year the Transcendental Meditation movement claimed more than 400,000 adherents, studying at more than 300 centers in the United States alone.

Millions more Americans, if skeptical about alternative medicine and Eastern spirituality, were still meditation-curious, and Dr. Benson, with his Ivy League pedigree and clinical approach to research, gave them license to indulge. The book sold more than four million copies and was a New York Times best seller.

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Dr. Herbert Benson, Who Saw the Mind as Medicinal, Dies at 86 - The New York Times

Steve Scott said the Midland community doesnt realize a lot of soccer parents and corporate employees are using marijuana products.

Scott is the owner/founder of Craft Hemp Company in downtown Midland, which sells hemp and CBD products. He has been on a long journey in this industry.

Scott began the business at a time when he was using chemotherapy to treat his cancer. Now, he uses his long history with marijuana as a survivor to spread awareness of the health benefits to Midland area residents.

Midland doesn't realize, there's a lot of moms that like to eat an edible at night, smoke a joint or use a vape pen, Scott said.

These are soccer moms. These are corporate employees, he said of Midland area parents and caregivers who visit his shop.

By not yet having opted in to allowing marijuana businesses in the city, he said Midland is missing out on an economic opportunity.

I hear that a lot of people go to Bay City or will get delivery services here, so (Midland is) losing out on a lot of money, Scott said.

Throughout the pandemic, Scott said theres been an increase of anxiety-related symptoms, which has caused some people to turn to his shop for relief.

He said first-time customers are stopping by daily, which has brought new faces into the Midland shop.

Business is great, Scott said.

But in terms of his personal gain, Scott said hed rather have a customer walk out with an open mind even though they might still be empty-handed.

I want to help people with a plant-alternative medicine, he said.

And some Midland area residents want to learn more about the hemp options. Scott said the Craft Hemp Co. is truly an education center that sells hemp and CBD products.

Craft Hemp sells high-end CBD and hemp products such as lotions, topicals and tinctures that can help with various ailments, based on both federal and state regulations. Whereas the marijuana industry medical and recreational dispensaries sells a variety of THC products and other goods.

Craft Hemp offers an in-shop consultation with customers to open the door for care catered to an individual.

He said the workers sit down with people and ask them questions to hear their current experiences with symptoms and provide a recommendation of dosage and protocols that fit.

Scott said its often during the consultation portion of a customers in-shop experience when peoples minds are more open to a non-pharmaceutical and/or non-mind-altering option.

(Customers might realize), They're actually caring about our quality of life, and that's when they start to get it, he said.

In order to enhance any given customers quality of life, Scott said he sources from a local farmer who is the gold standard.

Craft Hemp Co. works exclusively with Ag Marvels in Shepherd, which is the largest hemp farm within Michigans industry. This is Craft Hemp's go-to farmer, processor, and manufacturer of products to bring customers the farm to table experience of cannabis.

According to the hemp farms website, it was the first mover and pioneer in the hemp industry in Michigan.

Scott said Craft Hemp has built a great relationship with Ag Marvels as he believes its important to source from a Michigan-based group.

We make sure that we have the best products in here, he said.

One of the best-selling products at Craft Hemp is customizable CBD Tinctures.

We craft them right in front of you, Scott said.

In the customizable tinctures, theres a series of cannabinoids, which are chemical compounds of the cannabis plant. A plant contains more than 100 cannabinoids.

One of the well-known cannabinoids is Tetrahydrocannabinol, or THC, which is the compound that gives marijuana a psychoactive high.

Another chemical in marijuana is cannabidiol, or CBD. CBD does not cause a high and is often sold as a dietary supplement or included in creams, oils and other personal care products.CBD is also extracted from hemp, a plant in the cannabis family, which is low in THC.

Scott said CBD, CBG (which helps with anti-inflammation, cell growth and anti-bacteria) and CBN (which helps with insomnia, pain relief and muscle spasms) are commonly used to formulate a custom order. In addition, theres more than 40 flavors of oils to choose from.

Were kind of like what Baskin Robbins used to be back in the day, he said.

Marijuana is the dried flower of the cannabis plant and is used for both recreational and medical purposes.The hemp plant is also used outside of the marijuana industry. Fibers of the hemp plant are used in making rope, clothing, paper and other products.

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Sharing the health: Craft Hemp aims to improve quality of life for Midland residents - Midland Daily News

Near Darke

By Hank Nuwer

All married couples make one beautiful promise at the outset. Until death do us part.

My friends Jimmy and Karen made that same vow.

Unfortunately, each made a bad choice. Each put another before them.

Jimmy strayed first. Karen went to Jimmys friend-turned-enemy out of need or revenge.

Happily, their separation was brief.

The two were crazy about one another.

Jims greatest gift came after his bride was diagnosed with lung cancer.

Karens dream had been to own her own house. That never happened on Jimmys salary as a part-time sheriffs deputy and weekend roadhouse singer.

Now, Jimmy bought a squalid, ruined home built around 1890.

While Karen stayed in their rental home, he put on a roof, tore out the floorboards in the kitchen and replaced them with sheets of plywood. He adjusted loose doors so that they fit. He patched walls and ceilings.

The windows had gaps so wide that a loose receipt once floated off a table into the yard. He slapped on a ton of caulk.

After three months, Jimmy put in the touches that make a house a home.

He planted Karen a garden in front of a new picture window. He found an old birdbath in a thrift store so that she could watch birds from the couch.

He restored a fireplace that earlier couldnt have burned a log without setting the house on fire.

The day Jimmy moved Karen into her dream house, he raided the gardens of all his friends.

He put cut-glass vases of flowers on seemingly every shelf. Next to the toilet, where she now spent so much time, he put Karens favorite magazines in a wooden stand.

The gift of love energized Karen. Her fatigue lifted. She no longer stayed parked on the couch.

She used a rag much like the scarf that covered what fuzz she had left on her scalp.

She attacked dust alighting on the fireplace mantel, woodwork, and door tops.

Jimmy joked that she scrubbed the walls until the new paint grew thin.

One day in December, Karens doctor said he heard of an experimental drug. He cautioned them not to get their hopes too high.

Fat chance of that. It was their only hope.

Jimmy earmarked every cent for the medicine he prayed could cure his bride.

They scheduled a journey to a well-known cancer institute.

Jimmy helped Karen dress. He hurried her into the couples old Cadillac so the winter air didnt sear her brittle lungs.

The car was a clunker. Its corroded battery, chirping wheel bearings, and bad modulator valve made breakdowns inevitable, but Jimmy found parts in a junkyard to bring it back to life.

The couple parked the Caddy on the hospital lot. Karen took Jimmys left arm while his right held a briefcase stuffed with medical records.

A specialist examined Karen and all documents. He confronted Jimmy and the patient.

Karen is too far gone for experimental drugs, the specialist said. She had days, not months, left.

Jimmy pressed him with questions. What alternative treatments could he recommend maybe in Mexico?

None, none, the specialist said. Recommending an unproven drug would make him and the hospital open to a malpractice suit.

Jimmy wrote me at Christmas. He was shaking bushes worldwide to find some practitioner full of promises who would prescribe medications that might prolong her life the length of cut thread.

A thread of life is better than no life at all, he wrote.

In January, I wangled a magazine article that brought me two days to visit my friends. Karen wanted to show me her back.

My legs wobbled as I beheld her charred flesh.

I wondered if Jimmy would feel relief when his bride passed. I felt ashamed for wondering that.

Even as Karen lay like an inert pelt on the couch, her sighs and groans gave him hope for a miracle.

We cant accept a death sentence, Jimmy said. We wont.

I returned home as Karens energized days disappeared. Now Jimmy performed all the dusting.

Each day we search for a new normality and try to exceed it, he said. Shes going to have to be tougher than shes ever been just to stay even.

One day Jimmy bawled out Karens oldest son by a prior marriage. A long-haul driver, he hadnt been by the restored house even once to see his mother. Jimmy left only after extracting a promise from him.

Karen died one day after her sons visit. Perhaps she had stayed alive to see him once more.

Jimmy and Karen didnt have the unblemished happy ever after marriage.

But they sure were one anothers Valentine.

Hank Nuwer is an author, columnist and playwright. He and wife Gosia live on the Indiana side of the Union City state line. Viewpoints expressed in the article are the work of the author. The Daily Advocate does not endorse these viewpoints or the independent activities of the author.

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He loved her to death - The Daily Advocate

A European Union (EU) funded project is seeking to reduce animal testing within experimental medical research by means of 3D bioprinting.

Coordinated by the Institute of Bioengineering of Catalonia (IBEC), the BRIGHTER (Bioprinting by light-sheet lithography: engineering of complex tissues with high resolution and high speed) project is developing new 3D bioprinting processes for tissue engineering and regenerative medicine in order to reduce the use of animal models within these fields.

In particular, the project is focusing on fabricating human skin using a novel bioprinting technology based on patterned laser light sheets.

Our innovative 3D bioprinting system not only achieves tissues that are closer to the real ones, but it is also much faster than current systems, a fundamental factor to ensure the viability of the new tissues, said Professor Elena Martinez, Coordinator of the BRIGHTER project.

Reducing animal testing through AM

3D bioprinting has come on leaps and bounds over the past decade, with significant advances being made in the development of viable patient-specific tissues. While these developments hold promise for trialing the efficacy of drugs in the future, the tissues remain largely experimental and could still be decades away from human drug testing.

There is work being done within both academia and industry to change this, however, with the likes of Swedish bioprinter manufacturer CELLINK pledging to advance its research into animal cruelty-free cellular testing models, and the use of microscale skin models at the University of Stuttgart to trial the efficacy of cancer drugs in a bid to make animal testing obsolete.

Elsewhere, Fluicells Biopixlar platform has produced highly-complex neural models which could present future clinical drug screening applications, and UpNanos NanoOne Bio system is focusing on the fabrication of cell-culturing microstructures which could help reduce the number of animal experiments behind clinical trials.

A BRIGHTER alternative to animal testing

Alongside IBEC, Goethe University Frankfurt, Israels Technion center, and biotechnology firms Mycronic and Cellendes are also taking part in the BRIGHTER project. The initiative hopes to overcome many of the technical obstacles currently limiting the fabrication of complex human tissues.

The partners are working together to develop a novel Light Sheet Bioprinting process capable of producing complex and accurate in vitro models that can be used for cosmetics and drug testing within the pharmaceutical industry and in research settings.

To fine-tune the technology, the BRIGHTER team is endeavoring to 3D print human skin, which is a highly complex tissue made up of multiple cell types and structures, such as sweat glands and hair follicles. Hydrogels will form a key component of the bioprinting process as they form the base from which cells will grow and form new tissue, and can also be personalized to individual patients using their own cells.

To print the skin with the desired structure, shape and consistency, the researchers are using advanced imaging techniques that combine illumination with light sheets and high-resolution digital photomasks. By applying a laser directly into the hydrogel, the cells within it can be patterned and molded to the right shape, enabling the team to control the 3D printed structures stiffness, shape, and dimensions.

The ability to mold the hydrogel with high levels of detail is particularly crucial to the successful printing of human skin, as the tissue is made up of numerous layers with different cell types. According to the BRIGHTER team, their bioprinting process is also capable of generating vascularization of the printed tissue and enabling the function of the sebaceous and sweat glands, and the hair follicles to grow hair.

We hope to be able to print a skin sample with an area of 1cm and a thickness of 1mm in approximately 10 minutes and with cell viability of more than 95 percent, greatly improving current bioprinting conditions, said Dr. Nuria Torras, postdoctoral researcher at IBEC.

The BRIGHTER project hopes the successful printing of the in vitro skin models will validate their potential for use in both pharmaceutical and research environments, and ultimately reduce animal experimentation for drug and cosmetics testing.

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Featured image shows a small square of a matrix containing skin cells. Photo via IBEC.

Original post:

3D bioprinting project to deliver BRIGHTER alternative to animal testing - 3D Printing Industry

From her controversial therapy career to the tragic death of her first husband, this is the fascinating story of Princess Mrtha Louise of Norway, fourth in line to the throne.

If theres one thing that can be said about Princess Mrthe Louise, its that she seems to be a never ending source of inspiration for the tabloid press.

Whether its her love life, her business ventures or her public statements, she can arouse adulation as well as scorn from the general public.

Read on to find out more about her life, her works and why she has been at times such a controversial figure.

Read more: The Royal Family of Norway

Princess Mrtha Louise was born on September 22nd, 1971, at Rikshospitalet University Hospital in Oslo. She was named after her fathers mother, Crown Princess Mrtha, and her great-great grandmother, Queen Louise, the mother of King Haakon VII.

Rules of succession in place at the time of her birth meant that she was not in line for the throne, because she was female.

Changes made to the constitution in 1990 now stipulate that the first-born shall be first in the line of succession regardless of gender. This is why Princess Ingrid Alexandra, Crown Prince Haakons daughter, is third in line for the throne ahead of Mrtha Louise.

Since Mrtha Louise was born long before that constitutional amendment was adopted, it was decided that males would continue to take precedence over females for children born prior to 1990.

Interestingly, although Mrtha Louise was not in the line of succession for the Norwegian throne at the time of her birth, she was 26th in line for the British throne. This is because her father (Crown Prince Harald at the time and King Harald V now) is a second cousin of Queen Elizabeth.

If you want to learn more about this complex situation, check out this article about the connections between the British and Scandinavian Royals.

Princess Mrtha Louise spent her childhood at the Skaugum Estate, near Oslo. Her parents wanted their children to get a normal upbringing, and both the princess and her brother attended a municipal daycare centre and a local primary school.

The princess sang in a choir and played the flute. She joined a folk dancing group at the Norwegian Museum of Cultural History, and was an avid equestrian in her formative years.

The princess got engaged to Ari Behn (born Ari Mikael Bjrshol) in 2001, and got married to him at Nidaros cathedral in Trondheim on May 24th, 2002.

Ari Behn had achieved literary success in 1999 with a collection of short stories titled Trist som faen (Sad as Hell). This first book would remain his greatest literary success, praised by critics, while subsequent novels got mixed reviews.

During the early 2000s, he was often portrayed in Norwegian media as a pretentious poseur, frequently and flamboyantly arguing with critics and other artists. In a famous example of those public spats, he challenged critic Kjetil Rolness to a duel by pistol or sword in 2001.

Mrtha Louise obtained a royal edict in 2002 freeing her of her constitutional role and allowing her to start her own business. This means that Ari Behn never had an official title within the Royal household

The edict stipulates that Mrtha Louise is no longer a Royal Highness and has to pay income tax. She retains her place in the line of succession, and sometimes carries out representation duties on behalf of the king.

When travelling abroad, the princess is conventionally accorded the title Highness.

The couple had three daughters: Maud Angelica, Leah Isadora, and Emma Tallulah. None of them have an official royal title. The family lived in Islington, London, and Lommedalen, Brum.

On August 5th, 2016, the Royal Court announced that Princess Mrtha Louise and Ari Behn had started divorce proceedings and intended to share custody of their three daughters. The divorce was formalised the following year.

On December 26th, 2019, Ari Behns family issued a statement announcing that he had taken his own life the day before, on Christmas Day. He was 47. The news quickly made headlines around the world.

He had been known to struggle with alcoholism and depression for a number of years. In the days following his death, media reports about his life were plentiful and lavishly positive.

This led the National Association for Survivors of Bereavement by Suicide to raise the alarm, in fear of a contagion effect. At the same time, the Association praised the familys openness about the event.

American media reporting on Ari Behns death widely presented him as a Kevin Spacey accuser. This is due to a comment made by Ari Behn following the accusations of sexual misconduct made by 20 men against the American actor in 2017.

Ari Behn had described an incident in which he said Kevin Spacey had groped his genitals in 2007 at a nightclub during the afterparty for the Nobel Peace Prize concert.

Talking about the incident during a television interview, he said that he had not experienced it as sexual harassement, but rather as a compliment.

In 2019, Mrtha Louise made headlines once again by announcing that she was in a romantic relationship with self-styled shaman Durek Verrett.

The American claims to demystify spirituality by making it attainable and understandable not only for the layman, but also for the more spiritually advanced.

Verrett has been denounced as a charlatan in Norwegian media. Controversy also surrounded the couples use of the Mrtha Louises royal title in a commercial context. The princess later apologised on her Instagram account and ceased to use her title in this manner.

Princess Mrtha Louise became a certified physiotherapist in 1997, after getting a degree in Oslo and an internship in the Netherlands. She has never practised that profession, however, choosing instead to dedicate herself to other interests.

In 2000, she became a Rosen therapist Rosen therapy being a type of alternative medicine. This would not be her only foray into alternative beliefs, as she later claimed she could communicate with animals and angels.

In 2007, she started her own alternative therapy centre named Astarte Education, after one of the oldest goddesses in the Middle East. The centre offered people help to find their guardian angel.

This led to widespread criticism both from the University of Oslo, the Norwegian University of Science and Technology and even proponents of alternative medicine.

Read more: Famous Norwegian People

She replied to the criticism by stating in a TV interview that angels were creatures of light, which gave her a feeling of a strong presence and a strong and loving support. The school later changed its name to Soulspring and shut down a few years later following financial troubles.

In 2007, Mrtha Louise wrote history by becoming the first member of the Norwegian royal family to ever appear in a court of law. She succeeded through those legal proceedings to stop sales of a book entitled Martha's Angels, which used her photo on its cover without permission.

The book was the Norwegian translation of Seeing angels, by British author Emma Heathcote-James. The author herself said that she had no idea who the princess was, and that she did not understand why the book, originally published five years previously, was being launched in Norway at that time.

The Princess carries out official duties as a representative of the Royal household in areas concerning persons with disabilities. She is the chair of a fund that carries her name, and whose aim is to benefit children with disabilities.

She is also the patron of eight organisations, and a member of the board of Stiftelsen Vi(the Vi Foundation) which was established to help people with disabilities achieve equal rights to a meaningful life.

Link:

The Story of Princess Mrtha Louise of Norway - Life in Norway

Abstract

Follicular lymphoma (FL) is the most common indolent lymphoma and is characterized by a relapsing and remitting course. In addition to significant biologic heterogeneity, the clinical trajectory for patients is variable, with some being observed for many years, and others having aggressive disease requiring multiple treatment courses. Unfortunately, FL remains incurable, and continues to cause early mortality. Improved understanding of the genetic and immune biology of FL has led to several FDA-approved therapies in the relapsed and refractory setting, including PI3K inhibitors; immunomodulatory agents; the EZH2 inhibitor, tazemetostat; and anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, axicabtagene ciloleucel. This review outlines the current approach to the diagnosis and treatment of FL with a focus on emerging investigational therapies, including targeted protein inhibitors, antibody-drug conjugates, monoclonal antibodies, bispecific antibodies, and novel combination strategies.

Key Words: follicular lymphoma; treatment; novel therapies

Follicular lymphoma (FL) is an incurable B-cell lymphoid neoplasm with significant biological and clinical heterogeneity. As the most common indolent lymphoma and second most common non-Hodgkin lymphoma (NHL), it has a relapsing and remitting course with risk of transformation to aggressive disease.1,2 Most patients present with advanced disease and will eventuallyrequire treatment for symptomatic disease. Given the range of clinical behaviors, the decision of when to treat is equally important as how to treat, noting that therapeutic goals include meaningful remission, symptom palliation, and prolongation of life.

While the majority of patients have survival approximating 2 decades, a subset of patients have aggressive disease with poor outcomes.3 Unfortunately, baseline identification of these patients remains challenging. Approximately 20% of patients with FL have progressive disease within 2 years of initial chemoimmunotherapy and a 5-year overall survival (OS) of 50%.4 Cumulative toxicity from repeated exposure to palliative cytotoxic chemotherapy also contributes to morbidity and mortality. While antiCD20-based chemoimmunotherapy remains an important standard of care, more rational and biologically driven agents are either approved or in development. In this review, we examine the current approach to the diagnosis and treatment of FL with a focus on targeted therapy and other novel agents.

A diagnosis of FL requires histologic examination of a lymph node biopsy for assessment of nodal architecture and grading.5 FL is characterized by neoplastic germinal center B-cells growing in densely packed follicles with distortion of the normal nodal architecture. Grading depends on the number of centroblasts/high-power field. Grade 1-3a are considered indolent, whereas 3b is more aggressive and clinically approached as diffuse large B-cell lymphoma (DLBCL).6 The classic immunophenotype includes the B-cell antigens CD19, CD20, and CD79a; lymphoid progenitor marker, CD10; and nuclear proteins, BCL-2 and BCL-6. Unlike mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, it is negative for CD5.

Cytogenetically, FL is characterized by the translocation t(14;18), which occurs in up to 90% of cases, as a result of aberrant V(D)J recombination. This results in BCL-2 protein overexpression and increased cell survival (Figure 1).7 As a hallmark of FL, it is necessary, but alone insufficient, for lymphomagenesis.8-10 An important recent finding is early mutations in genes coding for chromatin modifying proteins.11-13 These epimutations are a second hallmark of FL and include: KMT2D (~70-80%), CREBBP (~65-70%), EZH2 (~25%), and EP300 (~14%).12,14 These transcriptionally repressive mutations result in increased germinal center proliferation, differentiation block, and immune evasion.15-17 Along with the BCL2 translocation, these mutations are early events occurring in a common progenitor cell.

Through divergent clonal evolution, other mutations are subsequently acquired including mutations in genes involved in immune modulation (TNFRSF14); JAK-STAT signaling (STAT6, SOCS1); and B-cell receptorNF-kB signaling (CARD11, TNFAIP3, MYD88).12 While conventional karyotyping and fluorescent in situ hybridization (FISH) for t(14;18) are part of the standard evaluation for FL, genomic sequencing is limited to testing for the EZH2 mutation when tazemetostat is being considered.18 Nonetheless, next-generation sequencing has revealed the diverse mutational landscape of FL and provides insight into disease pathogenesis, as well as opportunities for more precise therapeutic strategies.

The treatment of FL must consider individual parameters and balance the risk of cumulative toxicity versus remission and palliation of symptoms. The conventional approach to FL is clinical observation until there is an indication to treat, typically based on criteria of the Groupe dEtude des Lymphomes Folliculaires (GELF) or National Comprehensive Cancer Network (NCCN).19,20 There are several prognostic indices in FL including the Follicular Lymphoma International Prognostic Index (FLIPI), FLIPI-2, and m7-FLIPI, but none dictate the timing or type of treatment at an individual patient level.14,21,22

The m7-FLIPI and gene expression profiling panels include genomic features, but have varied performance and are not validated for clinical practice.23 Staging with positron emission tomography (PET) imaging helps to identify the extent of disease and preferred sites for biopsy when histologic transformation to DLBCL is suspected, as this occurs in up to 15% of patients.3 The assumption here is that higher uptake values correspond with more rapid cell turnover and aggressive histology. This is somewhat controversial, and PET alone does not appear to predict histologic transformation.24 Nonetheless, PET imaging does result in disease upstaging in approximately 10% to 60% of cases, which often has treatment implications.25,26

For patients with stage I-II disease, there are several options including observation, rituximab (Rituxan), chemoimmunotherapy, or radiation, with the majority of patients having similar excellent long-term survival regardless of initial approach.27 Approximately 70% of patients have advanced disease (stage III or IV) at diagnosis.3,28 Asymptomatic patients with low disease burden may be actively monitored. When treatment is indicated for patients with low tumor-burden advanced disease, rituximab monotherapy is often used, given the high overall response rate (ORR; complete remission [CR] plus partial remission [PR]) of 71%, low toxicity, and long median time to treatment failure of approximately 4 years, which delays the need for cytotoxic therapy.29

When selecting initial treatment for patients with high tumor burden and symptomatic advanced FL, there are several considerations regarding the chemotherapy backbone, the anti-CD20 antibody, the use of maintenance strategies, and whether to opt for a nonchemotherapy regimen (Figure 2). Based on the StiL (NCT00991211) and BRIGHT (NCT00877006) trials, bendamustine and rituximab (BR) or rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), are both options with ORR >90%.30,31

BR has become a preferred option based on superior progression-free survival (PFS) over R-CHOP (70 vs 31 months, respectively) and it is also not associated with alopecia, anthracycline-associated cardiotoxicity, vinca alkaloid-associated neuropathy, or steroid-associated risks. R-CHOP may be preferred in cases where occult transformation is suspected, or immune suppression associated with bendamustine is to be avoided. In patients treated with R-CHOP or rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP), maintenance therapy with rituximab every8 weeks for 2 years compared with placebo improves PFS, but not OS, based on the PRIMA study (NCT00140582).32

It is unclear whether this extends to patients treated with BR. In the GALLIUM study (NCT01332968), chemoimmunotherapy with obinutuzumab (Gazyva) versus rituximab improved PFS, with no difference in OS, but did result in high grade 3-5 adverse events, including infusion-related events and infections.33,34 The use of maintenance therapy is controversial, and even more so during the COVID-19 pandemic. Among surveyed physicians who treat indolent lymphomas with a maintenance therapy strategy, 53% hold rituximab maintenance to allow for vaccination.35 Lenalidomide (Revlimid)with rituximab is an alternative to chemoimmunotherapy with similar response rates, PFS, and OS to chemoimmunotherapy (R-CHOP, BR, or R-CVP).36 Similar to chemoimmunotherapy, it is a fixed-duration treatment, but with a much longer time frame at 18 months. It remains an option for patients wishing to avoid cytotoxic chemotherapy.

There is no standard treatment or sequence of treatments for relapsed/refractory FL (RR-FL), but the number of options is increasing. Approximately 20% of patients have early relapse and progression of disease within 24 months (POD24), and these patients have poor outcomes.4 Unfortunately, upfront identification of these patients is not possible, and more effective treatments for these patients are needed. For all patients with RR-FL, a chemoimmunotherapy regimen (BR, R-CHOP, or R-CVP) different from the first-line therapy is an option.

There is limited data on R-CHOP after BR, but second-line BR in patients with indolent NHL with previous rituximab (39%) or CHOP (54%) had an ORR of 82% and PFS of 34 months.37 Rituximab monotherapy is also effective for some patients with low tumor burden and previous rituximab-based regimens with an ORR 55% to 64% and PFS of 14 months.38,39 Obinutuzumab with either bendamustine or CHOP may improve outcomes by overcoming rituximab refractoriness, especially for relapses within 6 to 12 months.40,41 In transplant-eligible patients with chemosensitive disease to first salvage, consolidative autologous stem cell transplantation (auto-SCT) appears to improve long-term survival based on several retrospective analyses.

Among patients with POD24, auto-SCT has an improved 5-year OS of approximately 77% vs 59% among those without auto-SCT.42 Similar results were observed for patients undergoing auto-SCT within 1 year of treatment failure, with a 5-year OS of 73% compared with 60% without auto-SCT.43 It should be noted, however, that the benefit of auto-SCT may simply be due to a favorable response to second-line therapy and randomized studies are needed.

In the era of increased alternative treatments, the use of auto-SCT has been substantially reduced. The use of allogeneic-SCT, a historical option with curative potential in FL, has also declined. While the preferred therapy for high-risk patients with early relapse has yet to be defined, targeted therapy beyond anti-CD20 monoclonal antibodies has been reshaping the treatment landscape of FL since 2014 (Table 1), with several new trials focusing on this population, including a US Intergroup Study S1608 (NCT03269669).

Lenalidomide is an immunomodulatory drug with direct cytotoxicity to lymphoma cells via inhibition of the E3 ubiquitin ligase, cereblon, as well as indirect antitumor effects mediated through changes in the tumor microenvironment.44 Lenalidomide with rituximab is an active regimen in rituximab-sensitive relapsed FL, as demonstrated in the AUGMENT trial (NCT01938001) with an ORR of 80% (CR 35%) compared with an ORR of 55% (CR 20%) for rituximab alone.39 The combination had a 2-year OS and median PFS of 95% and 39.4 months compared with 86% and 13.9 months, respectively, for rituximab alone. The combination had a higher incidence of all grades of infections (63% vs 49%, respectively), neutropenia (58% vs 23%), and cutaneous reactions (32% vs 12%). Of the grade 3 or 4 adverse events, a higher incidence of neutropenia (50% vs 13%) was also observed with the combination. This study led to the regulatory approval of lenalidomide with rituximab in patients with RR-FL.

Inhibition of PI3K signaling has been a largely successful approach, with 4 FDA-approved agents in RR-FL.45 PI3K mediates proximal intracellular B-cell receptor signaling, as well as cell survival signals received from the tumor microenvironment. Idelalisib ( isoform inhibitor; Zydelig) was the first of these agents to be approved and a major breakthrough in the RR-FL space. The ORR was 57% (CR 6%) with a median duration of response (DOR) of 12.5 months and median PFS of 11 months in very heavily pretreated patients.46 Unfortunately, significant toxicities, including neutropenia, diarrhea, transaminitis, and pneumonia, limited its development. Copanlisib (pan-isoform inhibitor; Aliqopa); duvelisib ( and isoform inhibitor; Copiktra); and umbralisib ( isoform and CK1 inhibitor; Ukoniq) are also approved for RR-FL with comparable efficacy and improved toxicity profiles.47-49 They all have an ORR ranging from 42% to 59%, median DOR of 10 to 12 months, and median PFS of 9.5 to 11 months. They have regulatory approval for patients with multiply relapsed FL, based on activity in the heavily pretreated setting.

Approximately 25% of patients with FL have a gain of function mutation in the histone methyltransferase protein, EZH2, with consequent increased expression of genes involved in cell proliferation.12,14,50 Although it contributes to lymphomagenesis, EZH2 gene mutations are associated with improved PFS.50 Tazemetostat (Tazverik) is an EZH2 inhibitor that targets this epimutation. It is the first biomarker-directed therapy in FL and has been approved as a third-line option in RR-FL, with an ORR of 69% and CR rate of 13%.51 With a median follow-up of 22 months, the median PFS was 13.8 months, and median OS was not reached. It also appears to have activity in patients without an EZH2 gene mutation, with ORR of 35% and similar median PFS and OS. There were few significant treatment-related adverse events, with 3% of patients having grade 3 or 4 myelosuppression and a low discontinuation rate of 8%. Its favorable toxicity profile makes it an attractive oral option.

While targeted agents have clinical activity in RR-FL, long-term remission is still lacking and most require prolonged treatment courses. CAR T-cell therapy has revolutionized the treatment of aggressive lymphomas like DLBCL, and is also now an option for RR-FL, although follow-up remains short. Axicabtagene ciloleucel (axi-cel; Yescarta) is an anti-CD19 CAR T-celltherapy that received accelerated approval in March 2021 for adult patients with RR-FL ( 2 lines of prior therapy) based on the results of the phase 2 study ZUMA-5.52 In a preliminary report of updated results (median follow-up of 31 months), 86 patients with RR-FL had an ORR of 94% (CR 79%), median DOR and PFS of 38.6 months and 39.6 months, respectively, while OS was not reached.53 The incidence of cytokine release syndrome (CRS) and neurotoxicity grade 3 were 6% and 15%, respectively.

The phase 2 ELARA trial (NCT03568461) evaluating tisagenlecleucel (tisa-cel) in patients with RR-FL ( 2 lines of prior therapy) had an ORR 86% (CR 69%) without any grade 3 CRS, and only 3% with grade 3 neurotoxicity.54 At a median follow-up of 16.9 months, the median DOR, PFS, and OS were not reached, but 1-year PFS was 67%. The phase 2 TRANSCEND FL trial (NCT04245839) using lisocabtagene maraleucel is ongoing. One of the most crucial challenges is patient selection for CAR T, which remains a costly andaggressive approach. Long-term follow-up and real-world data for CAR T-cell therapy from the commercial setting will be important guides influencing patient selection.

Beyond the commercially approved targeted therapies in FL, there are multiple emerging agents that target the biology of FL (Figure 3). These are reviewed briefly in the following section, which also highlights novel investigational use of these treatments in FL (Table 2).

Antibody-drug conjugates (ADCs) offer an appealing means of antigen-based drug delivery, with several in development. In a phase 2 study in patients with RR-FL, the anti-CD79b ADC, polatuzumab vedotin, (pola; Polivy) was combined with rituximab and resulted in an ORR of 70% (CR 45%) with a 9.4-month DOR.55 The PFS was 15.3 months with a 2-year OS of 88%. The most common grade 3-4 adverse events were neutropenia (15%) and diarrhea (10%); however, although no grade 3-4 neuropathy was observed, 40% had grade 1-2 neuropathy.

In preliminary reports of early-phase studies evaluating pola combinations in RR-FL, pola with BR did not improve treatment response.56 Pola with obinutuzumab/lenalidomide had an ORR of 76% (CR of 65%), while pola with obinutuzumab/venetoclax had an ORR of 71% (CR of 57%), and long-term results with updated survival are anticipated.57,58 In a phase 1 study including 14 patients with RR-FL, the anti-CD19 ADC, loncastuximab tesirine (Zynlonta), had an ORR of 79% (CR of 65%), and cytopenias were the most common adverse effect.59

Although checkpoint blockade monotherapy has low response rates in RR-FL, combinations may be more active. A phase 1/2 trial (NCT02631577) using obinutuzumab, atezolizumab (Tecentriq), and lenalidomide (G-atezo-len) in patients with RR-FL reported an ORR of 78% (CR of 72%), median DOR of 38 months, and 2-year PFS of 65%.60 Cytopenias were the most common grade 3 adverse event and occurred in 71% of patients. While the majority of toxicities were manageable, the discontinuation rate of any study drug was 29%.

In a preliminary report of pembrolizumab with rituximab in patients with RR-FL (NCT02446457), the ORR was 80% (CR of 60%), and although safe, the benefit of pembrolizumab (Keytruda) over rituximab monotherapy was unclear, as this trial included patients with rituximab-sensitive disease.61 In the frontline phase 2 trial (1st FLOR study; NCT03245021), immune priming with nivolumab (Opdivo), followed by rituximab and nivolumab had an ORR of 92% (CR of 54%), with a favorable toxicity profile.62 Larger studies and a longer follow-up are needed to clarify the role of checkpoint inhibitors as first-line nonchemotherapy options.

Antibodies with novel targets are also under investigation in FL. The anti-CD47 antibody, magrolimab (Hu5F9-G4), blocks CD47 on lymphoma cells to enhance macrophage-mediated phagocytosis. In a phase 1 study of patients with RR-NHL, which included 7 patients with RR-FL, magrolimab with rituximab resulted in an ORR of 71% (5/7) and CR rate of 43% (3/7).63 Although small, these numbers are encouraging, with many patients having rituximab-refractory disease. The phase 2 portion of this study (NCT02953509) is currently recruiting.

Another trial investigating venetoclax (Venclexta) with obinutuzumab and magrolimab (VENOM) in relapsed/refractory indolent lymphomas is recruiting, and the results are eagerly anticipated (NCT04599634). Tafasitamab (Monjuvi) is an anti-CD19 antibody approved in combination with lenalidomide for relapsed/refractory DLBCL, but has low activity as a monotherapy in FL.64 A phase 3 trial (InMIND) of tafasitamab plus lenalidomide/rituximab versus lenalidomide/rituximab alone in patients with RR-FL or marginal zone lymphoma will determine whether there is a role for tafasitamab in RR-FL (NCT04680052).

Bispecific antibodies or bispecific T-cell engagers (BiTes) are novel protein constructs with separate B-cell (CD20) and T-cell targeting (CD3) domains. Mosunetuzumab, glofitamab, odronextamab, and epcoritamab are bispecific antibodies being investigated in early-phase RR-FL trials (Table 3), which have shown promising results with ORR ranging from 80% to 100% (CR from 50% to 75%) in heavily pretreated patients.65-69 Bispecific antibodies provide an off-the-shelf form of T-cell mediated therapy, with the goal of achieving the durable remissions seen with CAR T-cell therapy. Unlike CAR T-cell therapy, they appear to have a lower risk of CRS and neurotoxicity, and favorable responses in patients relapsing after CAR T-cell therapy. The optimal clinical use of bispecific antibodies remains unknown, and trials including novel combinations in FL are ongoing: mosunetuzumab and lenalidomide (NCT04246086); and epcoritamab with lenalidomide/rituximab or BR (NCT04663347).

While BCL2 translocation and epigenetic dysregulation are both frequent features in FL, the efficacy of existing agents has been modest. The BCL2 inhibitor, venetoclax, had low monotherapy activity in FL with an ORR of 38% (CR of 14%),70 but combination strategies are in development. A preliminary report of the first trial to combine a Bruton tyrosine kinase (BTK) inhibitor, ibrutinib (Imbruvica), with venetoclax in RR-FL showed an ORR of 83% (CR of 33%) with manageable toxicity (NCT02956382).71 Several frontline trials using venetoclax-based combinations include the following: venetoclax, oral azacitidine (CC-486), and obinutuzumab (NCT04722601); venetoclax, lenalidomide, and obinutuzumab (NCT03980171); and venetoclax, ibrutinib, and obinutuzumab (NCT04450173).

The phase 2 PrECOG 0403 trial with frontline venetoclax, bendamustine, and obinutuzumab (NCT03113422) for patients with high tumor-burden FL (n = 56) showed an ORR of 93% (CR of 73%), 2-year estimated PFS of 86%, and 2-year estimated OS of 94% at a median follow-up of 21 months.72 Despite the efficacy, the rate of grade 3 adverse events was high, at 84%, most notably due to tumor lysis, cytopenias, and infections. Unfortunately, this toxicity will preclude its use, but alternative dosing strategies to mitigate adverse effects are being explored. Tazemetostat is also being evaluated in combination with rituximab (NCT04762160), and in combination with lenalidomide and rituximab (NCT04224493).

While chemoimmunotherapy, lenalidomide with rituximab, or rituximab alone are standard first or subsequent line options for advanced FL, the treatment choices for RR-FL have evolved over the last several years. Additional agents for multiply relapsed patients include PI3K inhibitors, tazemetostat, and CAR T-cell therapy. Patient selection for CAR T-cell therapy is evolving, and the optimal sequencing with other therapies remains unknown. There are many emerging investigational products, including ADCs, anti-CD47 monoclonal antibodies, bispecific antibodies, checkpoint-based therapy, and novel combination strategies that are being evaluated. Individualized approaches, trial end points with quality-of-life measures, and information to guide sequencing of available regimens and agents are all desperately needed. These efforts, coupled with ongoing discovery in the biology of FL, are imperative to improving outcomes for patients with FL.

AUTHOR AFFILIATIONS:

Kirk E. Cahill, MD1; and Sonali M. Smith, MD1

1Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine Comprehensive Cancer Center, Chicago, IL.

Funding: None

Corresponding author

Sonali M. Smith, MD; Elwood V. Jensen Professor in Medicine; Chief, Section of Hematology/Oncology; Department of Medicine; The University of Chicago Medicine; 5841 S. Maryland Ave., MC 2115; Chicago, IL 60637; Email: smsmith@medicine.bsd.uchicago.edu

Continued here:

Follicular Lymphoma: a Focus on Current and Emerging Therapies - Cancer Network

What is butterbur?

Butterbur is a plant that grows in Europe and in some parts of Asia and North America. The leaves of the plant were traditionally used to wrap and protect butter in warm climates. This is where its name comes from.3

Throughout history, particularly in the Middle Ages and during the 17thcentury, butterbur has been used to treat a wide variety of ailments. During that time, it was used to treat fevers, coughs, asthma, skin conditions, and the plague.3

In the present day, there is particular interest in the use of butterbur for migraines and other headaches, allergic rhinitis, and other allergy symptoms.3

In a time when alternative remedies have become exceedingly common, everyone is looking for the next plant with potential. Considering butterburs history of medicinal use, there is no wonder that people are looking to this shrub next.

Some potential benefits of butterbur include reducing the frequency of migraines, improving symptoms of allergic rhinitis, and the treatment of anxiety and depression in people with particular psychiatric disorders.3-4Research has been done into each of these potential benefits and on the plant as a whole. It has been found that butterbur contains some compounds that do have medicinal effects on the body.4

Migraines are recurrent, throbbing headaches that are typically accompanied by nausea and visual disturbances.6 Those affected can face debilitating pain and may find it difficult to carry out their day-to-day activities. Migraines typically run in families and can affect both adults and children.

There is some evidence that butterbur, and its extracts, activate a certain protein channel in human cells, which can decrease inflammation in nerves.2It is believed that this is how butterbur has traditionally relieved migraine and headaches in some people.

Recent research has found that butterbur may have a place as a part of a holistic approach to the prevention of migraines.6

Allergic rhinitis is a condition caused by allergens. Some people refer to it as allergies. Allergic rhinitis may involve sneezing, runny or stuffy nose, or teary and itchy eyes. It often appears seasonally, in tandem with the growth of an individuals allergic triggers.4Much like with migraines, the severity of allergic rhinitis may vary and some people may find that the condition is so severe that it interferes significantly with their day-to-day lives.

Research has found that the leaves and roots of butterbur contain naturally occurring compounds that have medicinal effects. These compounds are referred to as petasins.4

When extracted and compared against a placebo in a double-blind clinical trial, one of these petasins has been found to have significant effects in reducing the severity of allergic rhinitis. It is believed that these petasins exhibit an anti-inflammatory effect, thereby reducing the bodys allergic response. However, this mechanism is not yet fully understood.4

Further studies are needed to prove the use of butterbur for allergic rhinitis, as conclusive evidence has been hard to come by.1

Butterbur is so widely recognized that in 2012 its use was recommended by the American Academy of Neurology to prevent migraines in adults and children. However, this recommendation was discontinued in 2015 as butterbur was found to have possible toxic effects on the liver.5These safety concerns have led to further analysis of the use of butterbur as alternative medicine.

It has been found that some products containing butterbur include toxic compounds called pyrrolizidine-alkaloids (PAs). These compounds can have many negative effects on the body, including damage to the liver, lungs, and blood vessels. They may also cause cancer.5

Fortunately, PA-free butterbur products do exist. These products have been deemed safe by some studies when taken for a period of up to 16-weeks.6

However, some products labeled as PA-free have tested positive for the toxic chemical. In addition, the long-term use of butterbur has not been extensively studied. PA-free butterbur products may have some mild side effects, including itchy eyes, diarrhea, fatigue, upset stomach, and drowsiness.1

Those with allergies to some plants may also find that they are allergic to butterbur. In particular, people who are allergic to ragweed, chrysanthemums, daisies, and marigolds should be cautious.3

Those who are pregnant and breastfeeding should avoid the use of butterbur products entirely. There is a risk of birth defects and liver damage for PA-containing products and PA-free products have not been studied in pregnant and breastfeeding populations.3

Like with any medication, alternative or otherwise, be sure to discuss butterbur with your healthcare provider. Your healthcare provider may tailor your plans to help achieve your health goals. You can work together to determine the correct treatment plan for you.

References

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Butterbur: An alternative treatment for headache and allergies? - Medical News Bulletin