Two years ago, when the first COVID-19 vaccines were administered marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through.
Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few.
It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, and more flexible and customizable.
“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.”
A paper published in Science reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus.
It’s all part of a National Institutes of Health-funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics.
“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.”
That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Hensley says.
How Do COVID-19 mRNA Vaccines Work?
Some of the COVID-19 vaccines are known as mRNA shots. How are they different from traditional vaccines? And do they contain the real virus?
Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.
Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died.
The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Hensley says, preventing severe illness if not infection overall.
Whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Levy cautions.
“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.
But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.
Your arteries and veins have a big job to do. They’re part of a transportation system that moves blood around. Arteries carry blood loaded with oxygen from your heart to the rest of your body. Veins deliver the blood, now without much of the oxygen, back to your heart. From there, the pulmonary artery sends it to your lungs to restock it with oxygen. Your pulmonary vein brings blood back to your heart, and the process starts again.
What Could Go Wrong?
2/16
Sometimes your arteries or veins get narrowed or blocked, and blood can’t go through them as easily. Any slowdown in blood flow keeps your organs from getting the oxygen and nutrients they need to do their job. If blood moves too slowly through the vessels, it can pool and form clots.
Coronary Artery Disease
3/16
You have this condition when sticky fat called plaque builds up in the walls of your coronary arteries — vessels that supply your heart with blood. Plaque narrows the arteries, slowing blood flow to the heart. When a piece of plaque breaks off and lodges in an artery, it can block blood flow completely and cause a heart attack.
Peripheral Artery Disease (PAD)
4/16
Peripheral arteries send blood to your arms and legs. In PAD, plaque builds up in artery walls. Just like in coronary artery disease, plaque narrows the arteries and leaves less room for blood to flow through. If your legs don’t get enough oxygen and nutrients, they’ll feel sore or tired when you walk or climb stairs. Having PAD raises your chance of getting a heart attack or stroke.
Carotid Artery Disease
5/16
The carotid arteries run along either side of your neck. They supply blood to your brain, face, and neck. If you have carotid artery disease, plaque builds up and narrows these arteries, so less blood gets through. A piece of plaque can break off and form a clot. If it gets stuck in a blood vessel to your brain and blocks blood flow, it can cause a stroke.
Cerebrovascular Diseases
6/16
Your brain needs a constant supply of oxygen-rich blood to work. Without it, brain cells die. Cerebrovascular diseases limit your brain’s blood supply. They include stroke, narrowed blood vessels, aneurysms (weakened arteries), and abnormal clusters of blood vessels called vascular malformations.
Varicose Veins
7/16
If you see thick, twisted, blue or flesh-colored veins in your legs, you may have varicose veins. Valves inside veins keep blood flowing toward your heart and prevent it from going backward. When your veins are weak, the valves can get damaged and allow blood to back up. As it collects, your vein swells up and twists to squeeze itself into the same small space. See your doctor if it hurts or you’re unhappy about the way you look.
Spider Veins
8/16
They’re like varicose veins, but thinner. They get their name from their spider web-like pattern. You get them when blood backs up in a damaged vein. They can form on your legs or face, and are usually red or blue. You’re more likely to get spider veins after an injury or a lot of time in the sun. Hormone changes during menopause or pregnancy can also cause them to form.
Blood Clots
9/16
When you get a cut, blood cells called platelets plug the hole in the damaged blood vessel with a clot that stops the bleeding. But sometimes, plaque can damage the inside of your blood vessels and cause a clot to form. This kind can be harmful. It can slow blood flow through your arteries and veins. And if one forms in your heart or brain, you might get a heart attack or stroke.
Thrombophlebitis
10/16
This condition happens when swelling and irritation cause a clot to form in one of your veins. You can get a clot after an injury, surgery, or if you’ve been on bed rest for a long time. It can form in veins close to the surface of your skin or deeper underneath it. Medicine called blood thinners can stop the clot from getting bigger and blocking your blood flow.
Deep Vein Thrombosis (DVT)
11/16
It’s a blood clot that forms in a deep vein, usually in your leg. You can get a DVT if you’ve been on bedrest after illness or surgery, or you sit for a long time in a plane or car. Lying or sitting for many hours slows your blood flow. Pooled blood can clump together and form clots. The risk with DVT is that a clot could break free and travel to your lungs.
Pulmonary Embolism (PE)
12/16
A blood clot in your legs can break off and travel all the way up to your lungs. When that happens, it’s called a pulmonary embolism. The clot can block the flow of blood in your lungs. Without blood, they can’t work as well as they should. They won’t be able to release enough oxygen to supply the rest of your body. PE can cause chest pain and shortness of breath. It could be life-threatening if you don’t get treated right away.
Chronic Venous Insufficiency (CVI)
13/16
Leg veins carry blood up to your heart. Valves in these veins shut to keep the blood flowing upward. When you have CVI, the valves don’t close all the way. Blood stops flowing up and instead pools in your veins. You can get CVI if a blood clot damages valves in your legs. Getting older or sitting for long periods of time can also weaken your leg veins and valves.
Aneurysm
14/16
It happens when an artery wall weakens and bulges out like a balloon. Aneurysms can form in many different blood vessels, including ones in your brain, chest, and belly. If the artery stretches too much, it can burst. That can lead to dangerous bleeding inside your body. An injury or artery disease can cause an aneurysm.
When to Call Your Doctor
15/16
Get medical help right away if you notice any of these things:
Sudden shortness of breath
Chest pain
Dizziness, fainting
Fast heartbeat
Sudden, severe headache
Nausea, vomiting
Sudden blurred or double vision
Sudden pain above or behind your eye
Trouble seeing in one or both eyes
Sudden weakness or numbness in your face or body
Trouble talking or understanding others
Seizure
Confusion
Protect Your Veins and Arteries
16/16
To avoid blood clots and other blood vessel problems, take care of your veins and arteries. Eat foods that are low in saturated fat. Exercise most days of the week. If you smoke, quit, because it can damage arteries. To prevent blood clots, avoid sitting for a long time. If you’re on a long flight or car trip, get up and walk now and then to keep your blood moving.
It’s when your blood sugar is higher than normal, but not high enough to be called diabetes. You won’t necessarily notice any symptoms — you can have it and not know it. A simple blood test can tell you if you do. You’re at risk if you’re overweight, over 45, and you don’t exercise. It makes you more likely to have type 2 diabetes and heart disease, but you can take steps to change that.
Lose Weight
2/8
It doesn’t have to be a lot. If you lose just 7% of your body weight, it can make a huge difference (that’s only 14 pounds for a 200-pound person). The first step is to eat healthier food with fewer calories. Start by keeping track of your weight, eating habits, and physical activities.
Eat Healthy
3/8
A good rule of thumb is to fill half your plate with non-starchy vegetables (asparagus, Brussels sprouts, and carrots, among many others). One quarter should have starchy foods (like potatoes, corn, or peas). The remaining quarter should be protein — chicken, fish, or beans are best. Be extra careful with carbs like baked goods or pasta — they can raise your blood sugar.
Exercise
4/8
You’ll lose weight faster and feel better if you get out and burn more calories. You don’t need to train for a marathon: A brisk 30-minute walk five times a week should do the trick. A workout buddy can sometimes help you stick to a routine, so call a friend or join a gym and make some new ones. Aerobic exercise (walking, swimming, dancing) and strength training (weight lifting, pushups, pull-ups) are both good. A little of both is best.
Get Your ZZZs
5/8
The right amount of shut-eye helps keep your blood sugar at healthy levels. If you can’t stay asleep, wake up too early, or get less than 5 hours a night, you’re more likely to get diabetes. About 7 or 8 hours a night is ideal. For better sleep, don’t have alcohol or caffeine late in the day, keep regular sleep hours, and stick to a calm, quiet bedtime routine.
Don’t Smoke
6/8
If you smoke, now’s the time to quit. Smokers are 30% to 40% more likely to get type 2 diabetes than nonsmokers. And if you get diabetes and still smoke, your symptoms may be worse and your blood sugar may be harder to control.
Medication
7/8
Certain drugs can help with blood sugar levels and obesity, as well as high cholesterol and high blood pressure. And you’re more likely to have those if you have prediabetes. If you do, take your medication as prescribed — it can improve your health and help you live longer.
Get Support
8/8
When you have people to share your good days and bad days with, it can make a big difference. Peer support groups can be a place to learn from others and get and give encouragement and understanding. Your doctor can help you find one that works for you.
Got sore muscles or a raging headache? Before you reach for that bottle in the medicine cabinet for pain relief, know what you’re taking — and what side effects it might cause. Always read the label and follow directions before taking any medication.
OTC Pain Reliever Types
2/12
Pain relievers come in two main varieties. Acetaminophen (Panadol, Tylenol) and nonsteroidal anti-inflammatory drugs — better known as NSAIDs — both help to relieve pain and reduce fever. NSAIDs include ibuprofen (Advil, Motrin), aspirin, and naproxen sodium (Aleve). Pain relievers come in many forms, including: tablets, caplets, gelcaps, and liquids.
Age Can Affect Pain Reliever Safety
3/12
Years ago, parents often gave their children baby aspirin for fevers and illness. Now that doctors know more about Reye’s syndrome — a rare but serious condition that affects the brain, kidneys, and liver — aspirin is a no-no for children and teens during times of illness. Sick kids can safely take ibuprofen and acetaminophen, as long as the dosage is right for their age and weight. Seniors also should use caution when taking OTC pain relievers, because older adults are more likely to develop side effects.
Drinks and Pain Relievers
4/12
Alcohol and OTC pain relievers can be a dangerous combination. Many drugs — including pain relievers — carry warnings about drinking alcohol if you are taking medication. Always read the label and follow instructions.
Pain Relievers Affect Blood Pressure
5/12
Some OTC pain relievers may interact with some high blood pressure medications or can increase blood pressure in people not previously diagnosed with this condition. If you take prescription high blood pressure drugs, regularly monitor your blood pressure and consult your doctor to find out what OTC pain medication would be best for you.
Stomachs Can Be Sensitive
6/12
Some NSAID pain relievers, such as ibuprofen and naproxen sodium, can be tough on your gut. They can irritate the lining of the stomach, leading to ulcers and bleeding, or aggravate ulcers you already have. If you have to use an NSAID pain reliever, help protect your stomach by taking the lowest possible dose for the shortest possible time and take them with food. If you need an NSAID daily for more than a week, check with your doctor.
Pain Relievers Can Overwork Kidneys
7/12
Your kidneys are two hard-working organs. They filter wastes and keep the balance of fluids and electrolytes, but NSAIDs can interfere with their ability to do these jobs. Regular use of these drugs can worsen kidney disease and lead to kidney failure. If you have chronic kidney disease, check with your doctor before using any NSAID pain reliever. More kidney-friendly alternatives may be available. Also, combining alcohol with acetaminophen can cause kidney damage. Be careful not to mix the two.
How Healthy Is Your Heart?
8/12
OTC pain relievers can be a double-edged sword for people with heart problems. Daily low-dose aspirin can help ward off blood clots that can lead to a stroke or heart attack. On the other hand, long-term non-aspirin NSAID use, especially at high doses, can interfere with the blood-thinning effect of aspirin. It can also boost blood pressure and increase the risk of heart attack or stroke. People with heart disease or high blood pressure should check with their doctor before taking NSAIDs. They are generally not recommended for people with kidney disease, heart failure, or cirrhosis.
Read Labels to Know Your Medicine
9/12
Combination over-the-counter products — such as cold and flu remedies — often contain several drugs. To avoid taking too much, look at the list of active ingredients. For example, if a medicine contains acetaminophen, you’ll know to avoid taking more separately. Reading labels can also help you avoid drugs you’re allergic to.
Liver Dangers With Pain Relievers
10/12
Acetaminophen-containing drugs and other pain relievers are usually safe and effective when used as directed, but all medications carry risks. Acetaminophen works great for pain relief, but it can affect your liver. Severe liver injury may occur if you take an overdose of acetaminophen. Always read the label and follow instructions. To prevent liver problems, don’t take more than the recommended total daily dose. Do not drink alcohol while taking acetaminophen-containing medications. And take the lowest dose possible for the shortest period of time. People with cirrhosis should avoid NSAIDs entirely and use acetaminophen only in small doses. Talk to your doctor to see which pain reliever is right for you.
Pregnancy and Pain Relief
11/12
When you’re pregnant, just about everything that goes into your body reaches your baby too. NSAIDS are not generally recommended for pregnant women during the third trimester due to an increased risk of complications in the newborn. If you’re in pain, check with your ob-gyn to evaluate the reason for your discomfort. There may be home remedies that can help, such as a massage or lukewarm soak for back pain. Before taking any pain reliever, check with your doctor to make sure it’s safe for you and your baby.
Drug Interactions
12/12
Some drugs just don’t play well with each other. Taking two that don’t mix can lead to dangerous interactions. For example, NSAIDs increase the risk of bleeding with the blood-thinner warfarin. And acetaminophen can also increase its effects. Because some drug interactions can be life threatening, tell your doctor or pharmacist about all the medications and supplements you’re taking, even over-the-counter drugs, vitamins, or herbal remedies.
A serving of drama with your holiday turkey? If your family fights, or going home triggers bad memories, you can cope.
Don’t expect the worst. Focus on catching up with a cousin or enjoying your favorite dish.
Make a plan. Have a trusted relative ready to spring you from bad conversations.
Set a time limit. Stop by for just 15 minutes. Or if you can’t bear to go, just RSVP “no.”
Over-Commercialization
2/10
When plastic reindeer and pressure to outdo last year’s gifts are just plain depressing, here are some ways to put the focus back on whatever’s meaningful to you:
Spend quality time with loved ones. Draw from your beliefs. Stick to simple traditions. Make a donation to charity instead of giving gifts.
Over-Committing
3/10
How to cope: Behold the power of “No.” Sounds silly, but practice saying it — out loud, in front of a mirror. Feel free to drop “no” to any holiday invitation. You don’t have to give a reason. Making a commitment to yourself to stay well-rested is healthy.
If there’s an obligation you feel you must honor but you’re still feeling overwhelmed, ask for help. Be specific. For example, “Can you bring the salad?”
Financial Worries
4/10
You don’t have to spend a lot — or even anything — to show you care.
Try: Buying books, personalizing by topic. Writing a thoughtful note or making gifts. Or scheduling a coffee or dinner with friends to enjoy one another’s company.
When shopping, create a budget early and stick to it. Scope out gifts online to avoid impulse buys in the mall frenzy.
Unrealistic Expectations
5/10
Life is hectic year-round. Add the pressure to produce a perfect holiday while also being merry and it’s easy to be left feeling bogged down, not festive.
Coping tip: Ditch perfectionism. No time to bake cookies for your son’s classmates? Store-bought cookies are just fine. Forgot the wreath? It’s OK. Your family will forgive you.
Fatigue
6/10
Staying up late wrapping presents, devoting days to make tins of chocolate treats for neighbors, or hustling through the mall can be exhausting and take its toll.
Coping tip: Take a breather. Remember, you can’t enjoy the holidays if you’re wading through them in a zombie-like fog. Make time to rest and revitalize. Plan nights in with no commitments and head to bed early.
Stress
7/10
Relatives. Shopping. Travel. Party planning. Finding childcare. Holidays can add to stress or sadness you feel during the regular year.
To survive: Plan daily “me time.” Just set aside 15 minutes to go walking or do something else you enjoy.
If you see a therapist, make arrangements to go more often if you feel you’ll need it. Or ask if you can do phone check-ins in case of crisis.
Breaking Healthy Habits
8/10
So you had an extra cup of eggnog. It’s OK. Don’t let a one-time holiday overindulgence derail the healthy habits you work on all year — like eating well, getting enough rest, and taking medications regularly.
Tips to get on track: Start fresh tomorrow. Try fresh veggies or fruit as a pre-party snack to curb buffet regrets. Avoid alcohol or know your limit. Keep a set exercise and eating routine.
Being Away from Family and Friends
9/10
If you can’t make it home this holiday or your friends have other plans, try:
Branching out. Celebrate with folks who will be in town and start a new tradition.
Looking ahead. Plan a visit in the New Year. Focusing on a future visit can take your mind off the present.
Volunteering. It places you around people and the emphasis on giving. Studies show helping others can help improve your mood and well-being.
Shorter Days, Lack of Sunlight
10/10
The darkness of winter really does affect some people’s moods. Sadness, anxiousness, loss of interest in activities, or sleeping more every winter can be a sign of depression called seasonal affective disorder (SAD). An estimated 10% – 20% of people in the U.S. experience a mild form of winter onset SAD, and it seems to be more common in women.
Coping tip: If you have symptoms, see your doctor. Treatment is available.
Everyone’s stomach gets a bit out of sorts from time to time. But in some cases, depending on your symptoms, you may need to see your doctor.
Gastritis
2/16
The liquid that helps you digest food has a lot of acid in it. Sometimes these digestive juices get through the protective barrier in your stomach and irritate its lining — that’s called gastritis. It can be brought on by bacteria, regular use of pain relievers like ibuprofen, too much alcohol, or stress. You can sometimes treat it with over-the-counter antacid or prescription medicines. But see your doctor because it can lead to bleeding or stomach ulcers.
Peptic Ulcer
3/16
These are open sores on the lining of your stomach or the upper part of your small intestine. The most common cause is bacteria, but again, long-term use of aspirin, ibuprofen, and other painkillers can play a role. And people who smoke or drink get these ulcers more often. They’re usually treated with prescription medicines that decrease stomach acid or antibiotics, depending on the cause.
Stomach Virus
4/16
Also known as the stomach flu, this is a viral infection in your intestines. You may have watery diarrhea, cramps, or nausea, and you might throw up. You can get it from someone who has it or contaminated food. There’s no treatment, but it usually goes away on its own. See a doctor if you have a fever, you’re throwing up, dehydrated, or you see blood in your vomit or stool.
Food Poisoning
5/16
Bacteria, viruses, and parasites in food cause this illness. You may have diarrhea, nausea, and vomiting. It happens when food isn’t handled properly. It usually gets better on its own, but see a doctor if you’re dehydrated, see blood in your vomit or stool, or you have diarrhea that is severe or lasts for more than 3 days. Also call your doctor if you have any symptoms of food poisoning and you have other health problems or have a weak immune system.
Irritable Bowel Syndrome
6/16
This common illness affects your large intestine (also called the colon). It can cause cramping, bloating, and mucus in your stool. You may go back and forth between diarrhea and constipation. It’s not clear why it happens, but food, stress, hormones, and infection may all play a part. A doctor may be able to help you control symptoms through changes in your diet or lifestyle, or medication.
Lactose Intolerance
7/16
Lactose is the sugar in milk and other dairy products. If you don’t have enough of an enzyme called lactase, your body can have trouble breaking it down. That can cause diarrhea, gas, bloating, and belly ache. There’s no cure, but you can manage it if you have only a small amount of dairy in your daily diet, buy lactose-free dairy products, or take over-the-counter lactaid pills.
Pelvic Inflammatory Disease
8/16
This happens to women: It’s inflammation of the reproductive organs, often following a sexually transmitted disease like chlamydia or gonorrhea. Besides pain in your belly, you might also have a fever, unusual discharge, and pain or bleeding when you have sex. If you catch it early, it can be cured, usually with antibiotics. But if you wait too long, it can damage your reproductive system.
Food Allergy
9/16
This happens when your body mistakes a certain food for something harmful and tries to defend against it. In addition to a stomachache, symptoms also can include tingling and swelling in your mouth and throat. In severe cases, it can cause shock and even death if it’s not immediately treated with a drug called epinephrine. Shellfish, nuts, fish, eggs, peanuts, and milk are some of the more likely triggers.
Appendicitis
10/16
Your appendix is a finger-shaped organ that is found at the beginning of your colon in the lower right part of your belly. It’s not clear what the appendix does, but when it’s inflamed, it’s usually infected and should be taken out. If it bursts, it can spread bacteria. Pain often starts at your belly button and spreads down and to the right. See a doctor immediately if you think you might have appendicitis.
Gallbladder Attack
11/16
This happens when gallstones — small rocks made from juices that help with digestion — block the tubes, or ducts, that run between your liver, pancreas, gallbladder, and small intestine. The most common symptom is abdominal pain — if it is severe or lasts more than several hours, call your doctor. You may also have nausea, vomiting, fever, tea-colored urine, and light-colored stools. The stones often move on their own, but you might need surgery if they don’t.
Incarcerated Hernia
12/16
A hernia happens when a part of your intestines slides through your abdominal wall. When it gets twisted or moved, and cut off from its blood supply, it can cause severe pain in your belly. Surgery is often needed quickly to correct the problem.
Constipation
13/16
Exercise, plenty of water, and foods that have a lot of fiber, like prunes and whole grains, can help. But if you regularly pass fewer than three stools a week, have to strain to go, and your stools are usually lumpy and hard, that can be a sign of a more serious condition. See your doctor if you have any of these.
Pancreatitis
14/16
This happens when your pancreas, an organ that helps your body process sugar and digest food, gets inflamed. You may have pain in your upper belly that gets worse after you eat. You may also have nausea, and you might throw up. Mild cases may go away on their own, but severe cases can be dangerous. Your doctor may ask you to stop eating for a day or two and give you pain meds. If that doesn’t clear it up, you might need to be in the hospital to get nutrition and fluids.
Inflammatory Bowel Disease (IBD)
15/16
Inflammatory bowel disease, or IBD, has two main forms: ulcerative colitis (UC) and Crohn’s disease. In both conditions, your immune system seems to overreact and inflame your intestinal tract. Though IBD doesn’t affect your stomach directly, belly pain and nausea are common symptoms, along with diarrhea, joint pain, fever, skin rashes, and other symptoms. Your doctor can help you manage your IBD with special medications along with lifestyle changes.
Diverticulitis
16/16
Small bulging pouches can form in the lining of your digestive system, usually in the lower part of your large intestine. They’re pretty common and don’t typically cause problems. But if they get inflamed or infected they can cause severe abdominal pain, nausea, and changes in bowel movements. Rest and changes in your diet can help. Your doctor might prescribe antibiotics as well.
Is your skin feeling dry and tight — even itchy or flaky? Any number of things can strip your skin of its protective oils. The result: Everything from chapped lips and itchy skin to cracked heels. Relief is in your grasp. Use this guide to see top cold-weather threats to your skin and what you can do about them.
SOS for Chapped Lips
2/18
No one is immune from dry lips in winter! Here’s how to cope: Drink plenty of water to stay hydrated and use a humidifier at home. Liberally apply beeswax or petroleum jelly to your lips. Put on lip balm or lipstick with sunscreen every time you go outside. Avoid being in the sun and wind too much. Don’t lick your lips — it may feel better briefly, but it only makes chapped lips worse.
Heal Cracked Heels
3/18
Painful, cracked heels are a common skin condition, especially in winter. They are often caused by dry skin. Having calluses around the rim of the heel can complicate the problem. In some cases, dry cracked feet can lead to infection or make walking painful. Keep feet healthy by marinating cracked heels in petroleum jelly, covering them with plastic wrap, and putting on a pair of socks overnight. You should see improvement in a few days.
Give Dry Hands Extra Care
4/18
Your hands may be hard hit by the cold winter air. Washing your hands frequently helps eliminate cold and flu germs, but it also increases dryness. And unless you wear gloves every time you go out, hands may be more exposed to cold than other parts of your body. Give dry hands some extra TLC by using a glycerin-based moisturizer when you wake up, before you go to bed, and any time your hands feel dry throughout the day.
Use Super-Fatted Soap
5/18
The same products that keep your face looking fresh in the spring and summer may cause skin problems during winter. Choose a gentle, super-fatted, fragrance-free soap — bar or liquid — for cleansing. Super-fatted means the soap is loaded with oils. Use a non-astringent toner, or just skip it altogether. If skin is dry, moisturizers that contain urea, dimethicone, glycerin, lanolin, or mineral oil can be good bets.
Choose a Winter Moisturizer
6/18
Should you change your moisturizer? Maybe. If you usually use a light lotion, try a heavier cream, at least on dry skin patches. Ointments — like petroleum jelly — have more oil than creams or lotions. That makes them more greasy, too, so they may be best for feet and body. Minimize the greasy feeling by using a very small amount and gently but thoroughly rubbing it into skin. Apply after a warm shower (more on that later).
Decode Moisturizer Choices
7/18
Humectants — like urea, glycerin, hyaluronic acid, propylene glycol — absorb water from the air. They are oil-free. Emollients — like baby or mineral oil, plant oils (like jojoba oil), petroleum jelly, lanolin, stearic acid — help replace oils in the skin. Many moisturizers contain a combination. You may want to skip some anti-aging moisturizers in winter. Those that contain retinoids can further irritate already dry, sensitive skin.
Clear Away Dead Skin First
8/18
To get the most out of your moisturizer, exfoliate. Clearing away dead skin cells lets a moisturizer better penetrate dry skin. Exfoliate gently with a moisturizer that contains lactic acid or salicylic acid. Some exfoliants can be irritating, especially in winter, so try them on a small patch of skin first. If your skin is really dry or irritated, ask your doctor before starting a new skin care product or regimen.
Winter Showers
9/18
A shower can add water to your skin — as long as you keep it short and sweet. Long, hot showers can actually draw moisture from your skin. Appealing as a hot shower on a cold morning may be, lukewarm water is a better choice. It won’t strip away skin’s natural oils.
Lock In Moisture After Your Bath
10/18
Right after you step out of the tub, pat skin dry and apply moisturizer to retain the water your skin just absorbed. A glycerin- or hyaluronic acid-based moisturizer can increase the amount of water that’s drawn into your skin. Baby oil (mineral oil) is also a good choice, because it prevents water from evaporating from your skin. Don’t stop there: Liberally re-apply moisturizer throughout the day, especially to troublesome dry skin patches.
Plug In a Humidifier
11/18
It’s cold outside! So you’re staying inside, with the heat on. That warm, dry air can mean parched, dry skin. Use a humidifier to restore moisture to the air. You can find inexpensive models at most drug stores. Put one in your bedroom; better yet, invest in two or three and place them strategically around your home to stave off irritated, itchy skin this winter.
Lube Your Locks
12/18
Protect your hair this winter by shampooing every other day instead of daily. Shampoos and excess shampooing can strip hair of moisture. Use warm water and a mild shampoo with sunscreen. Apply extra conditioner to keep your hair hydrated, shiny, and soft. Don’t overstyle with the blow dryer or flat iron. And protect your hair from the elements by wearing a hat.
Winter Sunscreen Required
13/18
Think you can’t get a sunburn in winter? Wrong. Skiers and other winter athletes are at special risk of sunburn because snow reflects sunlight. In fact, it bounces 80% of the sun’s rays back to us, compared to less than 20% for sand and surf. Even if you’re not hitting the slopes, you still need the protection of a sunscreen with an SPF of 30 or more. Apply daily, and reapply at least every two hours if you’re outside.
Bundle Up Against Frostnip
14/18
Frostnip, a mild form of frostbite, tends to affect the earlobes, cheeks, nose, fingers, and toes. Signs of frostnip include pale skin, numbness, or tingling in the affected area. Avoid frostnip by dressing warmly, including a hat, earmuffs, and gloves. The best treatment is to re-warm the affected areas. Although frostnip is uncomfortable, it doesn’t cause any damage to skin.
Be Alert for Frostbite
15/18
Frostbite is more serious and can cause lasting damage. Deeper tissues freeze, causing skin to become hard, pale, and cold. It may ache but lack sensitivity to touch. As the area thaws, it becomes red and painful. Hands, feet, nose, and ears are most vulnerable, but any body part can be affected. Treat frostbite by getting to a warm place, wrapping affected areas in sterile dressings (separate fingers and toes) and going to an emergency department immediately. Don’t rewarm affected areas if there’s a chance they could freeze again.
Beat the Itch of Winter Skin
16/18
Dry winter skin can be incredibly itchy. Beat itchy skin by taking a lukewarm bath with oatmeal or baking soda, reapplying your moisturizer frequently, and steering clear of wool and other rough fabrics. If these techniques don’t make a difference, see a dermatologist. You may have an underlying condition such as eczema or psoriasis that requires different treatment.
Show Eczema the Exit
17/18
Eczema is an umbrella term for different kinds of skin inflammation. It is marked by dry, reddened skin that itches or burns. When skin becomes dry and irritated in winter, eczema can flare. Stay one step ahead by moisturizing frequently with an oil-based ointment that contains sunscreen. Sweating and overheating can also trigger the itch/scratch cycle, so dress in easy-to-peel-off layers. Ask your dermatologist about prescription treatments.
Put Psoriasis in Its Place
18/18
Psoriasis is more than dry skin. It’s caused when the immune system misfires and speeds up skin cell growth. Dry air, lack of sunlight, and colder weather can make it worse. Follow tips for dry skin: short, lukewarm showers, lots of moisturizer, and humidifiers throughout the house. Ask your dermatologist about phototherapy, which uses ultraviolet light B (UVB) rays to slow the growth of skin cells, and about the best treatments for you.
Since the advent of glucocorticoid therapy for autoimmune disease in the 1940s, their widespread application has led to the concurrent therapy-limiting discovery of many adverse metabolic side effects. Unanticipated hyperglycemia associated with the initiation of glucocorticoids often leads to preventable hospital admissions, prolonged hospital stays, increased risks for infection and reduced graft function in solid organ transplant recipients. Challenges in managing steroid-induced diabetes stem from wide fluctuations in post-prandial hyperglycemia and the lack of clearly defined treatment protocols. The mainstay of treatment is insulin therapy coincident with meals.
This article aims to review the pathogenesis, risk factors, diagnosis and treatment principles unique to steroid-induced diabetes.
Keywords: steroid-induced diabetes, glucocorticoids, insulin resistance, new onset diabetes after transplant
Introduction
Glucocorticoids are extensively used in almost every subspecialty of medicine. Indications for short-term acute steroid therapy can be seen in exacerbation of chronic obstructive pulmonary disease, acute gout, chemotherapy protocols, bacterial meningitis and in pregnant women for fetal lung maturation, to name a few. Disease processes benefiting from chronic glucocorticoid use include the following: pulmonary diseases such as idiopathic interstitial pneumonia, hypersensitivity pneumonitis and sarcoidosis; autoimmune conditions; neurologic diseases such as myasthenia gravis and multiple sclerosis; and inflammatory bowel diseases. More recently, chronic glucocorticoid therapy plays an important role in modulating the immune system following solid organ transplantation. Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have various common metabolic side effects including hypertension, osteoporosis and diabetes. Steroid-induced diabetes mellitus (SIDM) has been recognized as a complication of glucocorticoid use for over 50 years [1].
Definition
Steroid-induced diabetes mellitus is defined as an abnormal increase in blood glucose associated with the use of glucocorticoids in a patient with or without a prior history of diabetes mellitus. The criteria for diagnosing diabetes by the American Diabetes Association [2] is an 8 h fasting blood glucose ≥ 7.0 mmol/L (126 mg/dL), 2 h post 75 g oral glucose tolerance test (OGTT) ≥ 11.1 mmol/L (200 mg/dL), HbA1c ≥ 6.5% or in patients with symptoms of hyperglycemic, a random plasma glucose of ≥ 11.1 mmol/L (200 mg/dL).
Prevalence
Given the widespread use of glucocorticoids in both the inpatient and ambulatory care setting, it is not surprising that at our 550-bed teaching hospital, approximately 40% of all inpatient consults to the Endocrinology Consult Service are for new onset steroid-induced diabetes or type 2 diabetes exacerbated by steroid use. This figure is consistent with the rate of 56% noted at other institutions [3].
The length of time on steroids, the relative potency of the glucocorticoid and the absolute dose all play a role in the occurrence of SIDM. In a retrospective study of 11 855 patients receiving various doses of glucocorticoids, Gurwitz et al. assessed the need of hypoglycemic therapy. The calculated odds ratio for patients receiving the equivalent of 50, 100 and greater than 120 mg of hydrocortisone daily were 3.02, 5.82 and 10.35, respectively, compared with controls [4]. In order to appreciate the magnitude of SIDM, one needs to consider that steroids cause predominantly post-prandial hyperglycemia and therefore, looking at impaired fasting glucose as the sole criteria, may underestimate the true incidence of SIDM.
Populations affected by chronic glucocorticoids
New onset diabetes after transplant (NODAT) is used to describe those patients in whom diabetes occurs for the first time in a post-transplant setting [5]. The incidence of NODAT is quite variable and likely underestimated because of lack of uniformity in the definition [6]. Varying immunosuppression protocols have caused discrepant incidence rates, although all agree that the incidence of NODAT is high in renal, liver, heart and lung transplant recipients (Table 1) [7–10]. In addition, the presence of NODAT has an adverse outcome on the survival of the transplanted organ as well as the health of the recipient [10].
Table 1
Examples of incidence of steroid-induced diabetes following solid organ transplantation
The population of patients following solid organ transplant is not the only population treated with glucocorticoids who develop SIDM: 12.7% of lupus patients [11], 14.7% of patients with respiratory ailments [10] and 23.5% of leprosy patients [12] developed diabetes following treatment with glucocorticoids. In addition, endogenous overproduction of glucocorticoids resulting in Cushing’s syndrome often translates to central obesity, muscle wasting, hepatic steatosis, hypertension and insulin resistance. In either overt or ‘subclinical’ Cushing’s 53% and 45% of subjects had either frank diabetes or impaired glucose tolerance, respectively [13].
Pathophysiology
The effect of glucocorticoids on glucose metabolism is likely the result of impairment of multiple pathways including beta cell dysfunction (sensitivity to glucose and ability to release insulin) and insulin resistance in other tissue.
Clinical studies
The role of beta cell function and other tissues’ sensitivity to insulin may be different depending on whether the glucocorticoid effect is acute or chronic. One study compared an acute single dose of prednisolone (75 mg) with 30 mg of prednisolone daily for 15 days. The acute treatment inhibited several parameters of beta cell function. Conversely, prolonged glucocorticoid exposure showed partial recovery of beta cell function but similarly impaired glucose tolerance, suggesting additional factors are important in SIDM other than beta cell dysfunction [14].
In addition to timing, the ‘glucocorticoid potency’ is a factor in the severity of post-glucocorticoid hyperglycemia. Yasuda et al. demonstrated that hydrocortisone, dexamethasone and prednisone result in varying degrees of insulin resistance based on decreased binding affinity of insulin rather than a decrease in receptor number [15].
Furthermore, normoglycemic men given a bolus of either cortisol or corticotropin releasing hormone (which causes an increase in endogenous cortisol) resulted in the expected elevation of plasma cortisol but caused an abrupt inhibition of insulin secretion even before there was a change in glucose concentration. Insulin resistance, measured by insulin secretion rate, developed 4–6 h after cortisol elevation and persisted for > 16 h [16].
In vitro studies
Further evidence for a direct effect of glucocorticoids on beta cell function has been from cultured rat insulinoma insulin-secreting, INS-1E cells [17]. Measurement of impaired insulin release in response to a glucose challenge was seen in prednisone-treated INS-1E cells. The inhibition was reversed in the presence of prednisone with the glucocorticoid receptor antagonist, RU486 [17]. The authors suggest that the defect may be due to impaired endoplasmic reticulum homeostasis, which in turn may lead to beta cell death.
Glyceroneogenesis
One of the etiologies of SIDM is based on the profound and reciprocal effect glucocorticoids have on glyceroneogenesis in liver and adipose tissue (Figure 1). In adipose tissue, glyceroneogenesis controls the rate of fatty acid release in the blood, while in the liver glyceroneogenesis is responsible for the synthesis of triacylglyerol from fatty acids and glycerol 3-phosphate [18]. The regulation of this process in both liver and adipose is via the enzyme phosphoenylpyruvate carboxykinase (PEPCK). In the presence of glucocorticoids, PEPCK gene expression in adipose tissue is suppressed, inhibiting glyceroneogenesis. In contrast, PEPCK in liver stimulates glycerol production and fatty acid concentration in the blood increased by the action of lipoprotein lipase [19]. The net result of glucocorticoids, therefore, is to increase the amount of fatty acids released into the blood. An increase in fatty acids interferes with glucose utilization and results in insulin resistance, especially in skeletal muscle. Thiazolidinediones promote expression of adipose and skeletal muscle PEPCK and reduce serum levels of fatty acids therefore reducing insulin resistance [20].
The effect of glucocorticoids on glycerneogenesis in adipose tissue and liver. Phosphoenylpyruvate carboxykinase (PEPCK) is reciprocally upregulated in liver and downregulated in adipose by glucocorticoids. This results in a buildup of free fatty acids in the blood, which in turn result in insulin resistance and increase gluconeogenesis
Molecular basis of glucocorticoid action on glucose regulation
The insulin-mediated pathways of glycogen synthesis and protein degradation and synthesis are directly influenced by glucocorticoids (Figure 2). Skeletal muscle is responsible for the majority of insulin-mediated glucose uptake. Insulin recruits GLUT4 glucose transporters to the cell surface enabling glucose uptake into cell. Glucocorticoids impair insulin-mediated glucose uptake by directly interfering with components of the insulin signalling cascade, such as glycogen synthase kinase-3, glycogen synthase and GLUT4 translocation [21,22]. An increase in protein degradation and decrease in protein synthesis is due to glucocorticoid inhibition of post-insulin receptor cascades involving PKB/Akt and mTOR pathways.
Risk factors for steroid-induced diabetes mellitus
Proposed risk factors for steroid-induced diabetes beyond cumulative dose and longer duration of steroid course include traditional risk factors for type 2 diabetes: older age, family history, high body mass index and impaired glucose tolerance [23]. The association with family history of diabetes is not well defined. Simmons et al. compared the demographics and clinical characteristics of patients with new onset SIDM with those with type 2 diabetes with and without steroid treatment. Those individuals who developed new onset SIDM had significantly less family history of diabetes when compared with individuals with type 2 diabetes mellitus and glucocorticoid treatment [24].
Concurrent immunosuppression
Other immunosuppressive agents can also affect glycemic control through other mechanisms, thus confounding impact of glucocorticoid therapy. In transplant patients, the use of calcineurin inhibitors (particularly tacrolimus) contributes to glucose intolerance by suppressing insulin production [24]. In those patients with systemic lupus erythematosis, patients on high-dose steroid therapy, development of diabetes was associated with concurrent use of mycophenalate mofetil, possibly attributed to impaired insulin secretion from increased beta cell stress [11,25].
Hypomagnesemia
Numerous studies have reported an inverse relationship between glycemic control and serum magnesium levels. Van Laecke et al. conducted a single-centre retrospective analysis consisting of 254 renal transplant recipients demonstrating that hypomagnesemia during the first month post-transplant was associated with the development of NODAT [26].
Hepatitis C virus
Liver disease contributes to impaired glucose tolerance, but there is evidence that chronic hepatitis C virus (HCV) infection itself is an independent risk factor for the development of diabetes in the general population and in liver transplant recipients [27,28]. A meta-analysis by Fabrizi et al. associated HCV seropositivity with a significantly increased risk of NODAT in kidney transplantation [29]. Baid et al. also demonstrated that the prevalence of NODAT was significantly higher in HCV positive patients (64% versus 28%) who underwent liver transplant [27].
The tendency for patients to develop new hyperglycemia in the setting of initiating glucocorticoid therapy is often not anticipated. In the elderly, without close follow-up or monitoring of blood sugars, there is a risk of precipitating hyperglycemic hyperosmolar states [30], which would require admission to the hospital for aggressive hydration and insulin therapy. It is generally thought that glucocorticoids result mainly in an increase in post-prandial blood glucose [31,32]. Use of continuous blood glucose monitor in COPD patients treated with prednisolone demonstrated that hyperglycemia predominately occurs in the afternoon and evening, indicating that this would be the most appropriate time to screen for SIDM as well as the period of time to direct specific treatment [33].
Strategies are needed to detect those at risk for developing steroid-induced diabetes before starting chronic therapy. The 2004 updated international consensus guidelines for NODAT suggest that pre-transplant evaluation include fasting plasma glucose, and when this is normal, an OGTT [22]. When OGTTs were performed in a cohort of renal transplant patients 1 week before and approximately 1 year after transplant, 23.7% of the patients had NODAT, which was associated with higher fasting and 2 h plasma glucose in the pre-transplant setting. Additionally, the ratio of proinsulin to insulin was higher at baseline in the patients that developed NODAT group [34].
Oral glucose tolerance testing should be performed as early as possible in post-transplant patients to detect diabetes in those deemed to be at risk [35]. In a cohort of renal transplant recipients 3 months post-transplant, Valderhaug et al. used the criteria of a fasting plasma glucose 95–124 mg/dL or an HbA1c greater than or equal to 5.8% to identify a subset that should undergo further diagnostic testing such as an OGTT [35].
New onset diabetes after transplant is a strong predictor of graft failure in the transplant population. Roth et al. reported 12-year graft survival in diabetic patients to be 48% versus 70% in controls [33]. Graft failure in the renal transplant population who develop NODAT is attributed to ongoing hyperglycemia leading to recurrent diabetic nephropathy [36].
One of the largest barriers to tapering glucocorticoids or switching to steroid-sparing immunosuppression to improve glucose control is the risk of allograft rejection [36], which itself is associated with increased risk for NODAT.
Diabetes is also associated with increased risk of cardiovascular events and a myriad of microvascular complications. The literature suggests that kidney transplant recipients who develop NODAT are at a twofold–threefold increased risk of fatal and non-fatal cardiovascular disease events as compared with non-diabetic patients [37].
Optimal treatment of SIDM warrants a different management strategy than non-steroid-induced diabetes. For instance, metformin, which is often used first-line in type 2 diabetes, is not recommended for SIDM because of its many relative or absolute contraindications, which include nausea/vomiting, hypoxia and liver or kidney disease. As noted previously in the discussion about glyceroneogenesis, the role of thiazolidinediones is yet to be fully explored.
Non-pharmacologic intervention
As with all types of diabetes, initial steps to improve glycemic control include lifestyle modification which includes exercise and dietary counselling to provide options that can perhaps lessen post-prandial hyperglycemia.
Insulin
Because initiation of glucocorticoids can cause post-prandial hyperglycemia and the tapering of glucocorticoids can lead to normalization of glycemic control, current guidelines may insufficiently address this. Basal bolus insulin therapy remains the most flexible option for patients and includes three components: basal insulin, prandial insulin and a supplemental correction factor insulin [38]. Conventional use of long-acting basal insulin with traditional weight-based dosing may cause nocturnal hypoglycemia [33]. More studies exploring dose titration of insulin in patients on glucocorticoids possibly utilizing technology like continuous glucose monitoring system are needed. In general, however, timing of glucocorticoids, to a midday or an evening meal with concomitant administration of intermediate acting insulin, is judicious.
Secretagogues
Oral secretagogues such as sulfonylurea therapy do not specifically target post-prandial hyperglycemia and thus long-acting agents may be associated with hypoglycemia if the patient does not eat meals regularly. For patients with mild hyperglycemia who are unable or unwilling to give injections of insulin, a trial of short-acting secretagogues such as nateglinide or repaglinide taken before meals could be considered [38].
Incretin mimetics
Incretin-based therapy with GLP-1 receptor agonists and DPP-4 inhibitors control glucose levels by stimulating insulin and inhibiting glucagon secretion in the fasting and post-prandial setting. A single dose of exenatide was able to improve glucose intolerance and insulin resistance in mice [39]. In humans, a randomized, double-blind, placebo-controlled trial was performed in which subjects on prednisone therapy received either the GLP-1 receptor agonist exenatide or saline [40]. Exenatide prevented prednisone-induced glucose intolerance and islet cell dysfunction primarily by decreasing glucagon and decreasing gastric emptying (Table 2) [40]. In the post-transplant setting, as more studies will be conducted with these and other agents, attention to drug–drug interactions is essential.
Table 2
Effect of prednisolone with and without exenatide following a mixed meal [40]
Molecule
Prednisolone only
Prednisolone + exenatide
Glucose
Increase
Decrease
Insulin
No change
Decrease
C-peptide
Decrease
Decrease
Glucagon
Increase
Decrease
Conclusion
As the therapeutic benefits of glucocorticoids continue to expand across medical specialties, the incidence of steroid-induced or steroid-exacerbated diabetes will continue to rise. Similar to non-steroid-related diabetes, the principles of early detection and risk factor modification apply. Diagnosing impaired fasting glucose or impaired glucose tolerance prior to the initiation of chronic glucocorticoids will better identify those who would benefit from steroid-sparing treatment, or if this is not an option, blood glucose monitoring while starting therapy. Further investigation into the precise mechanism of steroid-induced insulin resistance will provide insight into future diabetes prevention efforts and targeted therapies.
Painful diabetic neuropathy is frustratingly difficult to treat. Even the best prescription medication for the condition, gabapentin (Neurontin), only works for a small minority of those who try it, and some members of the diabetes community have never found anything that works. Patients that do find some relief often use a combination of prescription medication, over-the-counter treatments, and non-medicinal techniques such as massage or foot elevation.
Tim Swartztrauber tried it all, and he found no benefit from any of it. His diabetic neuropathy pain was so debilitating that it was robbing him of his life.
That all changed when his doctor suggested a trial of an uncommon treatment: spinal cord stimulation. Tim was an instant convert, and today he’s enjoying life again, his pain largely resolved.
[The manufacturers of Nevro HFX put Diabetes Daily in touch with Tim, but this is not a sponsored post. Tim is not a paid spokesman.]
Tim’s journey with diabetes had a traumatic beginning — a diagnosis of myelodysplastic syndrome and leukemia. His treatment odyssey eventually led to what was probably a case of steroid-induced diabetes. Steroids can cause hyperglycemia, and in Tim’s case, the effect was extreme.
“Back in 2015, I was diagnosed with leukemia. I had a bone marrow transplant and shortly after I developed graft versus host disease. I was on extremely high doses of steroids, and in January 2016 I was experiencing blurred vision and all that. I went in for an appointment. My blood sugar was 530 [mg/dL], and I had to stay in the hospital for seven days.”
Just when Tim thought he was getting his diabetes under control, his doctors ramped up his steroids usage again. With his blood sugar spiking back up to dangerous levels, he began to experience painful diabetic neuropathy.
“I was diagnosed with neuropathy, and it was severe. I had trouble walking. It was just miserable. It was 24 hours a day, I was only sleeping about two or three hours at a time. When I laid down to go to bed, my left foot hurt the worst, and I had to prop it up on my other foot so it wouldn’t touch the mattress.
“There were times I didn’t even want put on shoes because it hurt so bad. It would hurt to the touch. Just laying my foot on something would kill me.”
Tim tried a lot of different therapies to help with the pain, but nothing seemed to work.
“They had me on opioids, at one point I was taking 15mg of oxycodone four times a day, and it wasn’t even touching the pain. In my opinion, opioids don’t solve the problem, they don’t even mask the problem. All it did was make me sleepy and goofy. It’s not a quality of life you would want to have, living on pain medicines.
“I used gabapentin. I tried a cream I applied to my feet. It really didn’t help all that much.
“We tried some shots to my legs, hips, and ankles. I didn’t know there were steroids in those shots, and after I got the shots, my sugar went up to 589 and I had to go to the hospital again.
“I even went to a month’s worth of yoga. I did learn to relax a little more, but it didn’t really help.”
Although the degree of pain that Tim felt was unusual, the pattern of his general experience was typical. Many people with neuropathic pain find themselves trying all sorts of remedies, pharmaceutical and otherwise, sometimes with little success. (Opioids, probably the most commonly-prescribed treatment for painful neuropathy, are no longer recommended due to the danger of addiction and a lack of evidence that they are effective.)
“For a number of years, I didn’t do anything. I’d work and when I got home I’d just get in my chair and that was it.
“I was pretty miserable. Me and my wife were always at each other’s throats because I never wanted to do anything. I was really depressed. I started on depression medicine.
“Finally, my palliative care doctor referred me to a specialist who put me through a very thorough check. He mentioned the spinal cord stimulation implant.”
Spinal cord stimulation involves a small device that delivers mild electrical pulses along thin wires to the spinal cord. These pulses essentially block pain signals from reaching the brain. Spinal cord stimulation been used for years for many types of chronic pain (in the US, it is most commonly used for failed back surgery syndrome).
The scientific evidence in favor of spinal cord stimulation for people with diabetes is encouraging, but still emerging. A 2021 review noted that there have yet to be any blinded and randomized long-term trials of the technology, but observational trials suggest that many patients do enjoy long-lasting pain relief. The American Association of Clinical Endocrinology has recently endorsed high-frequency spinal cord stimulation as an option for people with “painful diabetic peripheral neuropathy that failed at least one medication.”
New patients undergo a trial period during which a temporary device is used to test the treatment. If everything goes well, a permanent device is surgically implanted underneath the skin. HFX reports that 90 percent of the patients that go through with a trial of the device decide to get the permanent implant.
“I did a trial. The next morning, I noticed that my feet didn’t hurt as bad. The next day they got better, and the next day they got a little better.”
When they removed the temporary device, the pain came back. “I decided right then and there that I was gonna get the implant.”
Tim says that the procedure was a snap, and only took a few hours: “The surgery is very easy, not very invasive, and not very painful.”
“The day after the implant was installed, my feet again got better. By the end of the week, I was like, ‘Oh my gosh, this is simply amazing.’ Every day it got better and better.
“I quit the gabapentin probably three to four days after surgery. Within a few months, I was totally off all pain meds. I don’t even hardly take aspirin. I’m off my depression meds.”
“My life has totally changed ever since.”
“Since the implant, that fall I went on a 10-day fishing trip with no problems whatsoever. You just don’t know how this really changed my life.”
The HFX Nevro implant comes with a remote control that Tim can use to modulate the type of pain relief he receives. He worked with his medical team to install multiple programs that target different parts of his body, so he can deliver relief where and when he needs it most.
“I charge it every night, it takes about 15 minutes a night. You have this belt with a power pack and you have this pad that you put right over your implant.”
He reports that the implant itself is unobtrusive. “It’s just a little square under my skin. It doesn’t bother me, I don’t even know it’s in there.”
“Now I’m sleeping 7 hours a night, straight through. It’s been amazing for me. I can’t really put it into words. I can’t say it enough, it’s just crazy.”
“This thing just totally changes your life. I was skeptical of this at first, but you have to try it. I would recommend, go through the trial, see how it helps you. Just give it a chance.”
A new genetic test may help determine which people with breast cancer can safely skip radiation after breast-conserving surgery to remove their tumor.
Individuals with invasive breast cancer who had low scores on an investigational gene panel were just as likely to experience a recurrence if they received radiation therapy after breast-conserving surgery or not, Swedish researchers report.
As it stands, people with this type of breast cancer typically have surgery to remove the cancer followed by radiation, to reduce the risk that their breast cancer will return in the same spot.
“For the first time, a genetic screening test can predict which patients can omit radiation,” said study author Dr. Per Karlsson. He is a professor of oncology at the Sahlgrenska Comprehensive Cancer Center and the University of Gothenburg in Sweden.
More research is needed before this gene test is ready for prime time, Karlsson said.
“We will confirm the findings in new cohorts, and we will also start prospective trials to be sure that this is correct, but it looks really promising,” he added.
For the study, researchers evaluated the predictive power of POLAR (Profile for the Omission of Local Adjuvant Radiotherapy), a 16-gene panel that was developed based on differences between people with and without local recurrence following breast-conserving surgery.
The study included 623 people from three trials whose cancer had not spread to their lymph nodes. Their breast cancers were also estrogen receptor-positive and HER2-negative. Their tumors were analyzed after surgery to see which genes were expressed.
Each person received a POLAR score based on this analysis, and then the researchers looked at the benefits of radiation therapy among those people with high and low scores.
The main finding? People with a high POLAR score can benefit from radiation therapy, while those with lower scores can likely skip it, the study findings showed.
People with high POLAR scores who received radiation therapy after breast-conserving surgery had a 63% lower risk of local recurrence compared with those who didn’t receive radiation. By contrast, there was no difference in recurrence rates seen among people with low POLAR scores, regardless of whether they received radiation or not. After 10 years, 5% of people with low scores who received radiation had a local recurrence, compared with 7% of those who didn’t, the investigators found.
It’s a win anytime a person can avoid radiation without risking a cancer recurrence, Karlsson said. “There are side effects for a small percentage of people, and if in the future we can omit radiation for some patients, it will be good for the quality of life,” he noted.
Besides being time-consuming, radiation may cause fatigue as well as skin side effects such as rashes, pain, redness and swelling.
The findings were scheduled for presentation Friday at the San Antonio Breast Cancer Symposium. Research presented at medical meetings should be considered preliminary until published in a peer-reviewed journal.
Breast cancer experts who reviewed the new study agreed that doctors are entering a new era in the diagnosis and treatment of breast cancer.
This type of genetic profiling of breast tumors is the future, said Dr. Julia Smith, a medical oncologist at NYU Langone Perlmutter Cancer Center in New York City. “We are trying to minimize the number of treatments that we are giving in certain subgroups based on molecular and genetic profiles of their cancer.”
This study helps define a subgroup of people who may not need radiation, she said.
“People with this type of breast cancer tend to do well to begin with,” Smith noted. “We need a larger group of women who we can follow for a longer time as people with these types of breast cancer usually don’t recur until more than 10 to 15 years later.”
Doctors don’t want to overtreat people, agreed Dr. Katherina Zabicki Calvillo, a breast surgeon and founder of New England Breast and Wellness in Wellesley, Mass. “We are really focusing on getting the best outcomes for patients with minimal toxicity and risk,” she said.
“It can be safe to omit radiation in certain populations. Although well-tolerated, radiation still has untoward side effects and affects the quality of life and return to work,” Calvillo explained. There may also be cost savings, she noted.
Calling the new study “interesting and important,” Dr. Marisa Weiss said the results can help tailor treatment recommendations about radiation. She is the chief medical officer and founder of Breastcancer.org in Ardmore, Pa.
“The POLAR 16-gene genomic test seems very promising in Swedish women,” Weiss said. “It will be important to test its validity in the much more heterogenous population within the U.S. before we can apply it to diverse populations with confidence.”
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