Modified electroconvulsive therapy (ECT) can reduce the risk for skeletal and dental fractures, new research shows.

Chittaranjan Andrade

“ECT is associated with a very low risk of skeletal fractures, even in high-risk patients, and is also associated with a low risk of dental fractures,” said study investigator Chittaranjan Andrade, MD, noting that preexisting bone and dental disease increase this risk.

Overall, clinicians who provide ECT “need to be aware of rare adverse effects, as well as the common ones,” Dr. Andrade, senior professor of clinical psychopharmacology and neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India, told this news organization. He added they also “need data to be able to provide reassurance.”

The findings were published online in The Journal of Clinical Psychiatry.


 

Avoid unmodified ECT

Dr. Andrade conducted the study because the risk of skeletal and dental fractures associated with ECT is “not commonly discussed.”

Although ECT is perhaps the most effective available treatment for major mental illness, it is associated with several adverse effects, including those associated with delivery of an electrical stimulus to the brain, which results in central and peripheral seizure, he noted.

“The central seizure is essential for the efficacy of ECT,” said Dr. Andrade. In contrast, “the motor seizure has no therapeutic value, is cosmetically displeasing, and may rarely be associated with peripheral adverse effects affecting muscles, joints, teeth, and bones,” he added.

The musculoskeletal and dental injuries are caused by stretching, twisting, compression, or direct injury. Particularly during the motor seizure, the “sudden jerk” associated with the tonic contraction of muscles as well as the repeated jerks associated with each clonic contraction can result in injuries, including skeletal and dental fractures.

To address this concern, the motor seizure is “modified” or attenuated through use of an intravenous muscle relaxant administered with other ECT premedication.

“How effectively the musculoskeletal and dental adverse effects are minimized depends on how well the motor seizure is modified,” Dr. Andrade said. He emphasized that the “use of unmodified ECT is strongly discouraged.”

Dr. Andrade reviewed prior research into the skeletal and dental risks of ECT. The infrequency of cases and ethical difficulties in conducting randomized clinical trials with such patients require reliance on anecdotal reports, he said.
 

Bite blocks, seizure modifiers

Population-based data showed that the fracture risk with modified ECT is two events per 100,000 ECTs. However, the risk may be as low as 0.36 events per 100,000 ECTs if calculated only with recent data, Dr. Andrade noted.

Population-based studies also suggest that the dental fracture risk with modified ECT is .02% per ECT and .17% per ECT course.

Although fractures have been reported under “unusual circumstances” among patients receiving modified ECT, many other reports point to the safety of this treatment, even in ultrahigh-risk patients.

Such patients include those with severe osteoporosis, metastatic bone disease, osteogenesis imperfecta, Ehlers-Danlos syndrome, Harrington rod implants, recent long bone fractures, multiple bone fractures, surgical repair of hip fracture, vertebroplasty, and maxillofacial repair.

Dr. Andrade noted that oral health is “poor” among patients with major mental illness for multiple reasons, including poor nutrition, self-neglect, and decreased salivation caused by the anticholinergic effects of medications.

This places these patients at increased risk for dental adverse effects during ECT because the muscles of the jaw contract forcefully during the motor seizure, causing sudden impact and, subsequently, sustained pressure on the teeth, Dr. Andrade said.

Moreover, because ECT is typically administered through repeated sessions, dental injuries may accumulate over the course of treatment.

ECT-associated skeletal risks arise from the tonic-clonic contractions of the muscles of the trunk and limbs, which need to be addressed via use of succinylcholine or other muscle relaxants included in ECT premedication.

Dr. Andrade noted that succinylcholine is effective at modifying the motor seizure at the common dose of 0.5-1.0 mg/kg. However, about 5% of patients require a higher dose (>1.5 mg/kg). If the dose is 1-2 mg/kg for patients at high risk for orthopedic complications, “muscle relaxation during ECT could be expected to be reasonably complete,” he said.

“Because of wide interpersonal variation, a neurostimulator may need to be used to identify the ideal dose for an individual patient,” he added.

In addition, use of bite blocks and effective jaw immobilization during ECT can reduce the risk. “Careful assessment of preexisting risk and good ECT practice can minimize the risk of skeletal and dental complications during ECT,” Dr. Andrade said.
 

Risks vs. benefits

Commenting on the study, Mark S. George, MD, distinguished professor of psychiatry, radiology, and neurology, and director of the brain stimulation division, Medical University of South Carolina, Charleston, said this was a “well-written review of how frequently patients who are undergoing modern ECT have bone fractures or dental fractures during the procedure.”

Dr. George, who was not involved with the research, added that modern medications and management “make ECT a truly safe procedure.”

“It is not without some risk, but these risks are low, especially when compared to the risks of untreated or undertreated depression or catatonia, like suicide,” he said.

Dr. Andrade publishes an e-newsletter supported by Sun Pharmaceuticals, with payments made directly to registered charities, but does not benefit financially from the relationship. His travel expenses for delivering lectures and workshops have been supported by the organizers themselves or pharmaceutical companies at the behest of the organizers. He has provided advice to various pharmaceutical companies and has received “nominal compensation.” He has also received payments for developing educational materials for scientific initiatives and programs, such as for the Behavioral and Neurosciences Foundation of India, PsyBase India, Texas Tech University USA, the Nordic Association for Convulsive Therapy, and the American Society of Clinical Psychopharmacology. Dr. George reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Modified electroconvulsive therapy (ECT) can reduce the risk for skeletal and dental fractures, new research shows.

Chittaranjan Andrade

“ECT is associated with a very low risk of skeletal fractures, even in high-risk patients, and is also associated with a low risk of dental fractures,” said study investigator Chittaranjan Andrade, MD, noting that preexisting bone and dental disease increase this risk.

Overall, clinicians who provide ECT “need to be aware of rare adverse effects, as well as the common ones,” Dr. Andrade, senior professor of clinical psychopharmacology and neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India, told this news organization. He added they also “need data to be able to provide reassurance.”

The findings were published online in The Journal of Clinical Psychiatry.


 

Avoid unmodified ECT

Dr. Andrade conducted the study because the risk of skeletal and dental fractures associated with ECT is “not commonly discussed.”

Although ECT is perhaps the most effective available treatment for major mental illness, it is associated with several adverse effects, including those associated with delivery of an electrical stimulus to the brain, which results in central and peripheral seizure, he noted.

“The central seizure is essential for the efficacy of ECT,” said Dr. Andrade. In contrast, “the motor seizure has no therapeutic value, is cosmetically displeasing, and may rarely be associated with peripheral adverse effects affecting muscles, joints, teeth, and bones,” he added.

The musculoskeletal and dental injuries are caused by stretching, twisting, compression, or direct injury. Particularly during the motor seizure, the “sudden jerk” associated with the tonic contraction of muscles as well as the repeated jerks associated with each clonic contraction can result in injuries, including skeletal and dental fractures.

To address this concern, the motor seizure is “modified” or attenuated through use of an intravenous muscle relaxant administered with other ECT premedication.

“How effectively the musculoskeletal and dental adverse effects are minimized depends on how well the motor seizure is modified,” Dr. Andrade said. He emphasized that the “use of unmodified ECT is strongly discouraged.”

Dr. Andrade reviewed prior research into the skeletal and dental risks of ECT. The infrequency of cases and ethical difficulties in conducting randomized clinical trials with such patients require reliance on anecdotal reports, he said.
 

Bite blocks, seizure modifiers

Population-based data showed that the fracture risk with modified ECT is two events per 100,000 ECTs. However, the risk may be as low as 0.36 events per 100,000 ECTs if calculated only with recent data, Dr. Andrade noted.

Population-based studies also suggest that the dental fracture risk with modified ECT is .02% per ECT and .17% per ECT course.

Although fractures have been reported under “unusual circumstances” among patients receiving modified ECT, many other reports point to the safety of this treatment, even in ultrahigh-risk patients.

Such patients include those with severe osteoporosis, metastatic bone disease, osteogenesis imperfecta, Ehlers-Danlos syndrome, Harrington rod implants, recent long bone fractures, multiple bone fractures, surgical repair of hip fracture, vertebroplasty, and maxillofacial repair.

Dr. Andrade noted that oral health is “poor” among patients with major mental illness for multiple reasons, including poor nutrition, self-neglect, and decreased salivation caused by the anticholinergic effects of medications.

This places these patients at increased risk for dental adverse effects during ECT because the muscles of the jaw contract forcefully during the motor seizure, causing sudden impact and, subsequently, sustained pressure on the teeth, Dr. Andrade said.

Moreover, because ECT is typically administered through repeated sessions, dental injuries may accumulate over the course of treatment.

ECT-associated skeletal risks arise from the tonic-clonic contractions of the muscles of the trunk and limbs, which need to be addressed via use of succinylcholine or other muscle relaxants included in ECT premedication.

Dr. Andrade noted that succinylcholine is effective at modifying the motor seizure at the common dose of 0.5-1.0 mg/kg. However, about 5% of patients require a higher dose (>1.5 mg/kg). If the dose is 1-2 mg/kg for patients at high risk for orthopedic complications, “muscle relaxation during ECT could be expected to be reasonably complete,” he said.

“Because of wide interpersonal variation, a neurostimulator may need to be used to identify the ideal dose for an individual patient,” he added.

In addition, use of bite blocks and effective jaw immobilization during ECT can reduce the risk. “Careful assessment of preexisting risk and good ECT practice can minimize the risk of skeletal and dental complications during ECT,” Dr. Andrade said.
 

Risks vs. benefits

Commenting on the study, Mark S. George, MD, distinguished professor of psychiatry, radiology, and neurology, and director of the brain stimulation division, Medical University of South Carolina, Charleston, said this was a “well-written review of how frequently patients who are undergoing modern ECT have bone fractures or dental fractures during the procedure.”

Dr. George, who was not involved with the research, added that modern medications and management “make ECT a truly safe procedure.”

“It is not without some risk, but these risks are low, especially when compared to the risks of untreated or undertreated depression or catatonia, like suicide,” he said.

Dr. Andrade publishes an e-newsletter supported by Sun Pharmaceuticals, with payments made directly to registered charities, but does not benefit financially from the relationship. His travel expenses for delivering lectures and workshops have been supported by the organizers themselves or pharmaceutical companies at the behest of the organizers. He has provided advice to various pharmaceutical companies and has received “nominal compensation.” He has also received payments for developing educational materials for scientific initiatives and programs, such as for the Behavioral and Neurosciences Foundation of India, PsyBase India, Texas Tech University USA, the Nordic Association for Convulsive Therapy, and the American Society of Clinical Psychopharmacology. Dr. George reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Modified electroconvulsive therapy (ECT) can reduce the risk for skeletal and dental fractures, new research shows.

Chittaranjan Andrade

“ECT is associated with a very low risk of skeletal fractures, even in high-risk patients, and is also associated with a low risk of dental fractures,” said study investigator Chittaranjan Andrade, MD, noting that preexisting bone and dental disease increase this risk.

Overall, clinicians who provide ECT “need to be aware of rare adverse effects, as well as the common ones,” Dr. Andrade, senior professor of clinical psychopharmacology and neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India, told this news organization. He added they also “need data to be able to provide reassurance.”

The findings were published online in The Journal of Clinical Psychiatry.


 

Avoid unmodified ECT

Dr. Andrade conducted the study because the risk of skeletal and dental fractures associated with ECT is “not commonly discussed.”

Although ECT is perhaps the most effective available treatment for major mental illness, it is associated with several adverse effects, including those associated with delivery of an electrical stimulus to the brain, which results in central and peripheral seizure, he noted.

“The central seizure is essential for the efficacy of ECT,” said Dr. Andrade. In contrast, “the motor seizure has no therapeutic value, is cosmetically displeasing, and may rarely be associated with peripheral adverse effects affecting muscles, joints, teeth, and bones,” he added.

The musculoskeletal and dental injuries are caused by stretching, twisting, compression, or direct injury. Particularly during the motor seizure, the “sudden jerk” associated with the tonic contraction of muscles as well as the repeated jerks associated with each clonic contraction can result in injuries, including skeletal and dental fractures.

To address this concern, the motor seizure is “modified” or attenuated through use of an intravenous muscle relaxant administered with other ECT premedication.

“How effectively the musculoskeletal and dental adverse effects are minimized depends on how well the motor seizure is modified,” Dr. Andrade said. He emphasized that the “use of unmodified ECT is strongly discouraged.”

Dr. Andrade reviewed prior research into the skeletal and dental risks of ECT. The infrequency of cases and ethical difficulties in conducting randomized clinical trials with such patients require reliance on anecdotal reports, he said.
 

Bite blocks, seizure modifiers

Population-based data showed that the fracture risk with modified ECT is two events per 100,000 ECTs. However, the risk may be as low as 0.36 events per 100,000 ECTs if calculated only with recent data, Dr. Andrade noted.

Population-based studies also suggest that the dental fracture risk with modified ECT is .02% per ECT and .17% per ECT course.

Although fractures have been reported under “unusual circumstances” among patients receiving modified ECT, many other reports point to the safety of this treatment, even in ultrahigh-risk patients.

Such patients include those with severe osteoporosis, metastatic bone disease, osteogenesis imperfecta, Ehlers-Danlos syndrome, Harrington rod implants, recent long bone fractures, multiple bone fractures, surgical repair of hip fracture, vertebroplasty, and maxillofacial repair.

Dr. Andrade noted that oral health is “poor” among patients with major mental illness for multiple reasons, including poor nutrition, self-neglect, and decreased salivation caused by the anticholinergic effects of medications.

This places these patients at increased risk for dental adverse effects during ECT because the muscles of the jaw contract forcefully during the motor seizure, causing sudden impact and, subsequently, sustained pressure on the teeth, Dr. Andrade said.

Moreover, because ECT is typically administered through repeated sessions, dental injuries may accumulate over the course of treatment.

ECT-associated skeletal risks arise from the tonic-clonic contractions of the muscles of the trunk and limbs, which need to be addressed via use of succinylcholine or other muscle relaxants included in ECT premedication.

Dr. Andrade noted that succinylcholine is effective at modifying the motor seizure at the common dose of 0.5-1.0 mg/kg. However, about 5% of patients require a higher dose (>1.5 mg/kg). If the dose is 1-2 mg/kg for patients at high risk for orthopedic complications, “muscle relaxation during ECT could be expected to be reasonably complete,” he said.

“Because of wide interpersonal variation, a neurostimulator may need to be used to identify the ideal dose for an individual patient,” he added.

In addition, use of bite blocks and effective jaw immobilization during ECT can reduce the risk. “Careful assessment of preexisting risk and good ECT practice can minimize the risk of skeletal and dental complications during ECT,” Dr. Andrade said.
 

Risks vs. benefits

Commenting on the study, Mark S. George, MD, distinguished professor of psychiatry, radiology, and neurology, and director of the brain stimulation division, Medical University of South Carolina, Charleston, said this was a “well-written review of how frequently patients who are undergoing modern ECT have bone fractures or dental fractures during the procedure.”

Dr. George, who was not involved with the research, added that modern medications and management “make ECT a truly safe procedure.”

“It is not without some risk, but these risks are low, especially when compared to the risks of untreated or undertreated depression or catatonia, like suicide,” he said.

Dr. Andrade publishes an e-newsletter supported by Sun Pharmaceuticals, with payments made directly to registered charities, but does not benefit financially from the relationship. His travel expenses for delivering lectures and workshops have been supported by the organizers themselves or pharmaceutical companies at the behest of the organizers. He has provided advice to various pharmaceutical companies and has received “nominal compensation.” He has also received payments for developing educational materials for scientific initiatives and programs, such as for the Behavioral and Neurosciences Foundation of India, PsyBase India, Texas Tech University USA, the Nordic Association for Convulsive Therapy, and the American Society of Clinical Psychopharmacology. Dr. George reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Get ‘em while they’re hot … for your health

Today on the Eating Channel, it’s a very special episode of “Much Ado About Muffin.”

The muffin. For some of us, it’s a good way to pretend we’re not having dessert for breakfast. A bran muffin can be loaded with calcium and fiber, and our beloved blueberry is full of yummy antioxidants and vitamins. Definitely not dessert.

Charles Rondeau/

Well, the muffin denial can stop there because there’s a new flavor on the scene, and research suggests it may actually be healthy. (Disclaimer: Muffin may not be considered healthy in Norway.) This new muffin has a name, Roselle, that comes from the calyx extract used in it, which is found in the Hibiscus sabdariffa plant of the same name.

Now, when it comes to new foods, especially ones that are supposed to be healthy, the No. 1 criteria is the same: It has to taste good. Researchers at the Norwegian University of Science and Technology and Amity University in India agreed, but they also set out to make it nutritionally valuable and give it a long shelf life without the addition of preservatives.

Sounds like a tall order, but they figured it out.

Not only is it tasty, but the properties of it could rival your morning multivitamin. Hibiscus extract has huge amounts of antioxidants, like phenolics, which are believed to help prevent cell membrane damage. Foods like vegetables, flax seed, and whole grains also have these antioxidants, but why not just have a Roselle muffin instead? You also get a dose of ascorbic acid without the glass of OJ in the morning.

The ascorbic acid, however, is not there just to help you. It also helps to check the researcher’s third box, shelf life. These naturally rosy-colored pastries will stay mold-free for 6 days without refrigeration at room temperature and without added preservatives.

Our guess, though, is they won’t be on the kitchen counter long enough to find out.

A sobering proposition

If Hollywood is to be believed, there’s no amount of drunkenness that can’t be cured with a cup of coffee or a stern slap in the face. Unfortunately, here in the real world the only thing that can make you less drunk is time. Maybe next time you’ll stop after that seventh Manhattan.

Cell Metabolism/Choi et al

But what if we could beat time? What if there’s an actual sobriety drug out there?

Say hello to fibroblast growth factor 21. Although the liver already does good work filtering out what is essentially poison, it then goes the extra mile and produces fibroblast growth factor 21 (or, as her friends call her, FGF21), a hormone that suppresses the desire to drink, makes you desire water, and protects the liver all at the same time.

Now, FGF21 in its current role is great, but if you’ve ever seen or been a drunk person before, you’ve experienced the lack of interest in listening to reason, especially when it comes from within our own bodies. Who are you to tell us what to do, body? You’re not the boss of us! So a group of scientists decided to push the limits of FGF21. Could it do more than it already does?

First off, they genetically altered a group of mice so that they didn’t produce FGF21 on their own. Then they got them drunk. We’re going to assume they built a scale model of the bar from Cheers and had the mice filter in through the front door as they served their subjects beer out of tiny little glasses.

Once the mice were nice and liquored up, some were given a treatment of FGF21 while others were given a placebo. Lo and behold, the mice given FGF21 recovered about 50% faster than those that received the control treatment. Not exactly instant, but 50% is nothing to sniff at.

Before you bring your FGF21 supplement to the bar, though, this research only applies to mice. We don’t know if it works in people. And make sure you stick to booze. If your choice of intoxication is a bit more exotic, FGF21 isn’t going to do anything for you. Yes, the scientists tried. Yes, those mice are living a very interesting life. And yes, we are jealous of drugged-up lab mice.
 

Supersize your imagination, shrink your snacks

Have you ever heard of the meal-recall effect? Did you know that, in England, a biscuit is really a cookie? Did you also know that the magazine Bon Appétit is not the same as the peer-reviewed journal Appetite? We do … now.

Stockvault

The meal-recall effect is the subsequent reduction in snacking that comes from remembering a recent meal. It was used to great effect in a recent study conducted at the University of Cambridge, which is in England, where they feed their experimental humans cookies but, for some reason, call them biscuits.

For the first part of the study, the participants were invited to dine at Che Laboratory, where they “were given a microwave ready meal of rice and sauce and a cup of water,” according to a statement from the university. As our Uncle Ernie would say, “Gourmet all the way.”

The test subjects were instructed not to eat anything for 3 hours and “then invited back to the lab to perform imagination tasks.” Those who did come back were randomly divided into five different groups, each with a different task:

• Imagine moving their recent lunch at the lab around a plate.
• Recall eating their recent lunch in detail.
• Imagine that the lunch was twice as big and filling as it really was.
• Look at a photograph of spaghetti hoops in tomato sauce and write a description of it before imagining moving the food around a plate.
• Look at a photo of paper clips and rubber bands and imagine moving them around.

Now, at last, we get to the biscuits/cookies, which were the subject of a taste test that “was simply a rouse for covertly assessing snacking,” the investigators explained. As part of that test, participants were told they could eat as many biscuits as they wanted.

When the tables were cleared and the leftovers examined, the group that imagined spaghetti hoops had eaten the most biscuits (75.9 g), followed by the group that imagined paper clips (75.5 g), the moving-their-lunch-around-the-plate group (72.0 g), and the group that relived eating their lunch (70.0 g).

In a victory for the meal-recall effect, the people who imagined their meal being twice as big ate the fewest biscuits (51.1 g). “Your mind can be more powerful than your stomach in dictating how much you eat,” lead author Joanna Szypula, PhD, said in the university statement.

Oh! One more thing. The study appeared in Appetite, which is a peer-reviewed journal, not in Bon Appétit, which is not a peer-reviewed journal. Thanks to the fine folks at both publications for pointing that out to us.
 

Get ‘em while they’re hot … for your health

Today on the Eating Channel, it’s a very special episode of “Much Ado About Muffin.”

The muffin. For some of us, it’s a good way to pretend we’re not having dessert for breakfast. A bran muffin can be loaded with calcium and fiber, and our beloved blueberry is full of yummy antioxidants and vitamins. Definitely not dessert.

Charles Rondeau/

Well, the muffin denial can stop there because there’s a new flavor on the scene, and research suggests it may actually be healthy. (Disclaimer: Muffin may not be considered healthy in Norway.) This new muffin has a name, Roselle, that comes from the calyx extract used in it, which is found in the Hibiscus sabdariffa plant of the same name.

Now, when it comes to new foods, especially ones that are supposed to be healthy, the No. 1 criteria is the same: It has to taste good. Researchers at the Norwegian University of Science and Technology and Amity University in India agreed, but they also set out to make it nutritionally valuable and give it a long shelf life without the addition of preservatives.

Sounds like a tall order, but they figured it out.

Not only is it tasty, but the properties of it could rival your morning multivitamin. Hibiscus extract has huge amounts of antioxidants, like phenolics, which are believed to help prevent cell membrane damage. Foods like vegetables, flax seed, and whole grains also have these antioxidants, but why not just have a Roselle muffin instead? You also get a dose of ascorbic acid without the glass of OJ in the morning.

The ascorbic acid, however, is not there just to help you. It also helps to check the researcher’s third box, shelf life. These naturally rosy-colored pastries will stay mold-free for 6 days without refrigeration at room temperature and without added preservatives.

Our guess, though, is they won’t be on the kitchen counter long enough to find out.

A sobering proposition

If Hollywood is to be believed, there’s no amount of drunkenness that can’t be cured with a cup of coffee or a stern slap in the face. Unfortunately, here in the real world the only thing that can make you less drunk is time. Maybe next time you’ll stop after that seventh Manhattan.

Cell Metabolism/Choi et al

But what if we could beat time? What if there’s an actual sobriety drug out there?

Say hello to fibroblast growth factor 21. Although the liver already does good work filtering out what is essentially poison, it then goes the extra mile and produces fibroblast growth factor 21 (or, as her friends call her, FGF21), a hormone that suppresses the desire to drink, makes you desire water, and protects the liver all at the same time.

Now, FGF21 in its current role is great, but if you’ve ever seen or been a drunk person before, you’ve experienced the lack of interest in listening to reason, especially when it comes from within our own bodies. Who are you to tell us what to do, body? You’re not the boss of us! So a group of scientists decided to push the limits of FGF21. Could it do more than it already does?

First off, they genetically altered a group of mice so that they didn’t produce FGF21 on their own. Then they got them drunk. We’re going to assume they built a scale model of the bar from Cheers and had the mice filter in through the front door as they served their subjects beer out of tiny little glasses.

Once the mice were nice and liquored up, some were given a treatment of FGF21 while others were given a placebo. Lo and behold, the mice given FGF21 recovered about 50% faster than those that received the control treatment. Not exactly instant, but 50% is nothing to sniff at.

Before you bring your FGF21 supplement to the bar, though, this research only applies to mice. We don’t know if it works in people. And make sure you stick to booze. If your choice of intoxication is a bit more exotic, FGF21 isn’t going to do anything for you. Yes, the scientists tried. Yes, those mice are living a very interesting life. And yes, we are jealous of drugged-up lab mice.
 

Supersize your imagination, shrink your snacks

Have you ever heard of the meal-recall effect? Did you know that, in England, a biscuit is really a cookie? Did you also know that the magazine Bon Appétit is not the same as the peer-reviewed journal Appetite? We do … now.

Stockvault

The meal-recall effect is the subsequent reduction in snacking that comes from remembering a recent meal. It was used to great effect in a recent study conducted at the University of Cambridge, which is in England, where they feed their experimental humans cookies but, for some reason, call them biscuits.

For the first part of the study, the participants were invited to dine at Che Laboratory, where they “were given a microwave ready meal of rice and sauce and a cup of water,” according to a statement from the university. As our Uncle Ernie would say, “Gourmet all the way.”

The test subjects were instructed not to eat anything for 3 hours and “then invited back to the lab to perform imagination tasks.” Those who did come back were randomly divided into five different groups, each with a different task:

• Imagine moving their recent lunch at the lab around a plate.
• Recall eating their recent lunch in detail.
• Imagine that the lunch was twice as big and filling as it really was.
• Look at a photograph of spaghetti hoops in tomato sauce and write a description of it before imagining moving the food around a plate.
• Look at a photo of paper clips and rubber bands and imagine moving them around.

Now, at last, we get to the biscuits/cookies, which were the subject of a taste test that “was simply a rouse for covertly assessing snacking,” the investigators explained. As part of that test, participants were told they could eat as many biscuits as they wanted.

When the tables were cleared and the leftovers examined, the group that imagined spaghetti hoops had eaten the most biscuits (75.9 g), followed by the group that imagined paper clips (75.5 g), the moving-their-lunch-around-the-plate group (72.0 g), and the group that relived eating their lunch (70.0 g).

In a victory for the meal-recall effect, the people who imagined their meal being twice as big ate the fewest biscuits (51.1 g). “Your mind can be more powerful than your stomach in dictating how much you eat,” lead author Joanna Szypula, PhD, said in the university statement.

Oh! One more thing. The study appeared in Appetite, which is a peer-reviewed journal, not in Bon Appétit, which is not a peer-reviewed journal. Thanks to the fine folks at both publications for pointing that out to us.
 

Get ‘em while they’re hot … for your health

Today on the Eating Channel, it’s a very special episode of “Much Ado About Muffin.”

The muffin. For some of us, it’s a good way to pretend we’re not having dessert for breakfast. A bran muffin can be loaded with calcium and fiber, and our beloved blueberry is full of yummy antioxidants and vitamins. Definitely not dessert.

Charles Rondeau/

Well, the muffin denial can stop there because there’s a new flavor on the scene, and research suggests it may actually be healthy. (Disclaimer: Muffin may not be considered healthy in Norway.) This new muffin has a name, Roselle, that comes from the calyx extract used in it, which is found in the Hibiscus sabdariffa plant of the same name.

Now, when it comes to new foods, especially ones that are supposed to be healthy, the No. 1 criteria is the same: It has to taste good. Researchers at the Norwegian University of Science and Technology and Amity University in India agreed, but they also set out to make it nutritionally valuable and give it a long shelf life without the addition of preservatives.

Sounds like a tall order, but they figured it out.

Not only is it tasty, but the properties of it could rival your morning multivitamin. Hibiscus extract has huge amounts of antioxidants, like phenolics, which are believed to help prevent cell membrane damage. Foods like vegetables, flax seed, and whole grains also have these antioxidants, but why not just have a Roselle muffin instead? You also get a dose of ascorbic acid without the glass of OJ in the morning.

The ascorbic acid, however, is not there just to help you. It also helps to check the researcher’s third box, shelf life. These naturally rosy-colored pastries will stay mold-free for 6 days without refrigeration at room temperature and without added preservatives.

Our guess, though, is they won’t be on the kitchen counter long enough to find out.

A sobering proposition

If Hollywood is to be believed, there’s no amount of drunkenness that can’t be cured with a cup of coffee or a stern slap in the face. Unfortunately, here in the real world the only thing that can make you less drunk is time. Maybe next time you’ll stop after that seventh Manhattan.

Cell Metabolism/Choi et al

But what if we could beat time? What if there’s an actual sobriety drug out there?

Say hello to fibroblast growth factor 21. Although the liver already does good work filtering out what is essentially poison, it then goes the extra mile and produces fibroblast growth factor 21 (or, as her friends call her, FGF21), a hormone that suppresses the desire to drink, makes you desire water, and protects the liver all at the same time.

Now, FGF21 in its current role is great, but if you’ve ever seen or been a drunk person before, you’ve experienced the lack of interest in listening to reason, especially when it comes from within our own bodies. Who are you to tell us what to do, body? You’re not the boss of us! So a group of scientists decided to push the limits of FGF21. Could it do more than it already does?

First off, they genetically altered a group of mice so that they didn’t produce FGF21 on their own. Then they got them drunk. We’re going to assume they built a scale model of the bar from Cheers and had the mice filter in through the front door as they served their subjects beer out of tiny little glasses.

Once the mice were nice and liquored up, some were given a treatment of FGF21 while others were given a placebo. Lo and behold, the mice given FGF21 recovered about 50% faster than those that received the control treatment. Not exactly instant, but 50% is nothing to sniff at.

Before you bring your FGF21 supplement to the bar, though, this research only applies to mice. We don’t know if it works in people. And make sure you stick to booze. If your choice of intoxication is a bit more exotic, FGF21 isn’t going to do anything for you. Yes, the scientists tried. Yes, those mice are living a very interesting life. And yes, we are jealous of drugged-up lab mice.
 

Supersize your imagination, shrink your snacks

Have you ever heard of the meal-recall effect? Did you know that, in England, a biscuit is really a cookie? Did you also know that the magazine Bon Appétit is not the same as the peer-reviewed journal Appetite? We do … now.

Stockvault

The meal-recall effect is the subsequent reduction in snacking that comes from remembering a recent meal. It was used to great effect in a recent study conducted at the University of Cambridge, which is in England, where they feed their experimental humans cookies but, for some reason, call them biscuits.

For the first part of the study, the participants were invited to dine at Che Laboratory, where they “were given a microwave ready meal of rice and sauce and a cup of water,” according to a statement from the university. As our Uncle Ernie would say, “Gourmet all the way.”

The test subjects were instructed not to eat anything for 3 hours and “then invited back to the lab to perform imagination tasks.” Those who did come back were randomly divided into five different groups, each with a different task:

• Imagine moving their recent lunch at the lab around a plate.
• Recall eating their recent lunch in detail.
• Imagine that the lunch was twice as big and filling as it really was.
• Look at a photograph of spaghetti hoops in tomato sauce and write a description of it before imagining moving the food around a plate.
• Look at a photo of paper clips and rubber bands and imagine moving them around.

Now, at last, we get to the biscuits/cookies, which were the subject of a taste test that “was simply a rouse for covertly assessing snacking,” the investigators explained. As part of that test, participants were told they could eat as many biscuits as they wanted.

When the tables were cleared and the leftovers examined, the group that imagined spaghetti hoops had eaten the most biscuits (75.9 g), followed by the group that imagined paper clips (75.5 g), the moving-their-lunch-around-the-plate group (72.0 g), and the group that relived eating their lunch (70.0 g).

In a victory for the meal-recall effect, the people who imagined their meal being twice as big ate the fewest biscuits (51.1 g). “Your mind can be more powerful than your stomach in dictating how much you eat,” lead author Joanna Szypula, PhD, said in the university statement.

Oh! One more thing. The study appeared in Appetite, which is a peer-reviewed journal, not in Bon Appétit, which is not a peer-reviewed journal. Thanks to the fine folks at both publications for pointing that out to us.
 

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

Introduction

The COVID-19 pandemic has changed the healthcare system in a multitude of ways, affecting healthcare capacity, treatment of other illnesses, and wellness as well as professional retention of healthcare workers.^1-3 During the peak of the COVID-19 pandemic, healthcare capacity was tested and resources were used up quickly.¹ As the pandemic has progressed, healthcare systems have had to decide how to proceed with lessons learned, reassessing the environment of care delivery, healthcare supply chains, workforce structures, communication systems, and scientific collaboration as well as policy frameworks in healthcare.⁴ 

There have been both immediate effects and long-term consequences of the delay in care for other conditions.^2,5 One stark example of this is in cancer care, where screening and procedures were postponed or canceled due to the pandemic with a resulting predicted 2% increase in cancer mortality in the next 10 years.² The care of heart disease, chronic illnesses, and other viruses has also been similarly negatively impacted by the COVID-19 pandemic due to similar delays in diagnosis and treatment.^5-7 

The impact on healthcare workers has also been profound.³ Occupational stress from the pandemic has correlated with increased depression and posttraumatic stress disorder (PTSD) among other mental health diseases in healthcare workers.³ In a survey of neurosurgery residents, 26.1% of physicians reported feeling burnt out, and 65.8% were worried that they would not be able to reach surgical milestones.^8,9 Among respiratory therapists, a hard hit group during this time, 79% reported burnout.¹⁰ Additionally, more healthcare workers left the field during the pandemic, with 15 million lost jobs. Future recovery of jobs looks bleak in some settings, like long-term care and among assistants and aides.¹¹ Overall, the long-term outcomes of these resource, disease, and mental health disruptions need to be assessed and solutions created to maintain a quality and effective healthcare system, with ample resources and measures to account for disease increases and address the impact on providers. 

Healthcare Capacity and Resources 

With COVID-19 affecting over 100 million in the United States as of March 1, 2023, the impact on healthcare resources since the start of the pandemic has been immense.¹² With 5% to 38% of hospitalized patients being admitted to the intensive care unit (ICU) and 75% to 88% of those patients requiring mechanical ventilation, a huge strain was placed on resources during and after the pandemic.¹ 

The question of balancing resources for other hospital needs while tending to patients with COVID-19 has been an ongoing discussion at many levels.¹ One core resource concern is the lack of staff. In a survey of 77 different countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%), 15% reported insufficient intensivists and 32% reported insufficient ICU nursing staff during March and April of 2020.¹ A lack of hospital and care space that led to reallocation of limited-care acute care space was a concern. Thirteen percent reported a shortage of hospital ICU beds, while others reported the conversion of postoperative recovery rooms (20%) and operating rooms (12%) for patients with COVID-19.¹ 

Along with staff and care space concerns, hospital survey respondents reported that healthcare equipment was also challenged. Access to COVID-19 testing was one concern, with only 35% of respondents reporting availability for all patients at the beginning of the pandemic, and 56% reporting availability for only select patients based on symptom severity.¹ Access to personal protective equipment (PPE) was also affected, with PPE always available according to 83% to 95% of respondents but just 35% having access to N95 masks.¹ Additionally, 26% reported that there were no respirators in their hospital, and 11% reported limited ventilators.¹ 

Although resource depletion is a problem, studies have looked at public health measures that helped to mitigate this issue. With proper public health planning and implementation, such as physical distancing, aggressive testing, contact tracing, and increased hospital capacity, by freeing up existing resources or adding additional support, public health modeling showed that resources may be able to withstand the increase.¹³ Development of reallocation models at local, state, national, and international levels is an important step to be able to deal with future public health crises.¹⁴

The long-term impact from the pandemic includes disruption in the physical environment of healthcare, production, supply chain, staff structure, and workforce alterations.⁴ For example, the physical shape of healthcare facilities is changing to accommodate increasing volumes and decrease the risk of spreading disease.⁴ To accommodate the burden on staffing structure and workforce alteration, telehealth gained a prominent role.⁴ All in all, the pandemic has changed the healthcare system; however, institutions, organizations, and policy makers need to evaluate which measures were impactful and should be considered for long-term inclusion in healthcare practice. 

Impact on Other Diseases: Cancer, Heart Disease, Chronic Illnesses, and Other Viruses 

The treatment of other new and existing conditions has also been affected by the pandemic. Cancer, especially, is a disease of concern. Elective surgeries and screening were halted or altered during the pandemic, which is modeled to lead to higher cancer mortality in years to come.² The most affected cancers were breast, lung, and colorectal cancer.² A study of colorectal cancer screening showed that colonoscopies were delayed due to COVID-19 and that gastroenterology visits declined by 49% to 61%.¹⁵ This will likely lead to delayed cancer diagnoses and possible increases in mortality.¹⁵ Breast cancer screening was also delayed and many patients continued to avoid it for various reasons such as fears of contracting COVID-19 infection in healthcare facilities, and the economic effects of the pandemic such as job loss and healthcare coverage loss.¹⁶ These delays will result in an estimated potential 0.52% overall increase in breast cancer deaths by 2030.¹⁷

A study of 368 patients from Spain showed a 56.5% decrease in hospital admissions, usually related to heart attacks, in March and April of 2020, compared to January and February 2020.^18,19 For other chronic illnesses, the pandemic resulted in decreased preventative care and management.²⁰ The care of other infections similarly suffered. The World Health Organization announced that the number of patients receiving treatment for tuberculosis (TB) dropped by 1 million, setting the disease mitigation back considerably.²⁰ An estimated 500,000 more people died in 2020 from TB.²¹ The drastic shift in focus to COVID-19 care during this period will continue to have a profound impact on other diseases like these for many years post-pandemic.

Provider Experience and Mental Health Outcomes 

The impact on provider experiences and mental health has been immense. One study of 510 healthcare providers (HCPs) and first responders found that occupational stress from the pandemic correlated with psychiatric symptoms, including depression, PTSD, insomnia, and generalized anxiety.³ Occupational stress also correlated with one’s likelihood to leave the medical field and trouble doing work they had once loved.³ Half of the healthcare workers surveyed indicated a decreased likelihood of staying in their current profession after the pandemic.³ 

Other studies have also looked at specific subspecialties and impact on trainees during the pandemic. In neurosurgery, for example, resident burnout is high, at 26.1%.⁹ Additionally, the lack of surgeries in the pandemic made 65.8% of neurosurgery residents anxious about meeting career milestones.⁹ Respiratory therapists, a highly impacted group, also experienced burnout, reporting higher levels in those who worked more in the ICU. Another study identified several themes in the concerns reported by healthcare workers during the pandemic era including “changes in personal life and enhanced negative affect,” “gaining experience, normalization, and adaptation to the pandemic,” and “mental health considerations.”²² 

Some studies have investigated ways to mitigate this dissatisfaction with the healthcare field post-pandemic. Intrapreneurship, reverse mentoring, and democratized learning all had a reported positive impact on employee experience and retention during this time.²³ Intrapreneurship describes entrepreneurship within an existing organization, while reverse mentoring and democratized learning refer to newer employees teaching older employees and communicative learning on a breadth of topics. Other studies have examined the necessity of having mental health resources available, and that these resources need to be multi-stage and individualistic as well as specific to certain stressors HCPs faced during the pandemic.²² 

Conclusion and Future Directions

The COVID-19 pandemic had stark effects on the healthcare system, impacting resources and capacity, care of other diseases, and provider mental health and experiences.^1-3 After the chaos of the pandemic, many questions remain. What needs to be done now by health systems and HCPs? How can we learn from the challenges and the effects on capacity to change the healthcare workflow in times of crisis and in the present? How do we mitigate the impact of the pandemic on diagnosis and management of diseases? And how do we continue to provide healthcare workers with proper mental health and professional resources now, not just in times of stress, and encourage the future generation to pursue careers in healthcare? 

These are all the questions the pandemic has left us with, and more studies and initiatives are needed to investigate solutions to these issues. The COVID-19 pandemic left behind valuable lessons and changed the healthcare system, disease management, and staffing for many. Now is the time to pick up the pieces and strategize on how to make our existing system more effective for workers and patients post pandemic. 

LGBTQ advocates across North America aim to boost stem cell donation by reminding community members they are welcome to give – and that gay men don’t face the same restrictions as they’ve faced, at least thus far, in donating blood.

In fact, gay men have been able to donate stem cells in the United States since 2015. That’s when National Marrow Donor Program’s Be the Match registry lifted restrictions on men who have sex with men (MSM).

Physicians say advocacy is still necessary, because LGBTQ people may assume they can’t donate or be wary of clinicians. “The LGBTQIA+ population in general has experienced a lot of issues with the medical-industrial complex in terms of discrimination and inappropriate care,” said UT Southwestern Medical Center pathologist Brian Adkins, MD, who manages the blood bank at Children’s Health in Dallas, in an interview. “There’s a weariness there that may produce some hesitancy to interact with the donation process.”

An estimated 6.8 million people give blood in the United States each year, and an estimated 9 million people are registered as potential stem cell donors. A total of 22,013 hematopoietic cell transplantation procedures were performed in 2020, according to the U.S. Health Resources and Services Administration.

Expanding the number of LGBTQ donors, especially those born as biological males, could pay major dividends. As Dr. Adkins noted, the ideal stem cell donor is young – Be the Match says doctors generally prefer donors aged 18-35 – and male. According to a 2021 Gallup Poll, 21% of those born from 1997 to 2003 (Generation Z) say they’re LGBTQ, as do 11% of those born from 1981 to 1996 (Millennials).

In North America, the most extensive outreach to the LGBTQ community about stem cell donation has been launched in Canada. There, an organization called Stem Cell Club focuses on encouraging college students and other young people to register as potential stem cell donors.

Stem Cell Club has several campaigns aimed at ethnic minority groups, and its Saving Lives With Pride project focuses on MSM. The project’s web page includes testimonials from a woman whose life was saved by an unrelated gay male donor and from a gay male nurse who recovered from blood cancer thanks to a stem cell donation. The site also includes videos about stem cell donation featuring LGBTQ young people and Canadian hematologists.

“Our specialized collection center will treat donors with the highest levels of respect and courtesy, indeed as heroes of their unselfish gift that can truly save a life,” says Ottawa Hospital transplant hematologist David Allan, MD, in one of the videos.

Stem Cell Club was founded by transplant hematologist Warren Fingrut, MD, a research fellow at Memorial Sloan Kettering Cancer Center. In an interview, he said the organization’s LGBTQ project has promoted stem cell donation at several annual gay pride events and will continue the outreach this coming summer. In 2018 and 2019, advocates recruited 354 potential stem-cell donors (40% male, 42 non-White) at five pride events, Dr. Fingrut and colleagues reported last year in the journal Bone Marrow Transplantation.

For a new study, researchers interviewed 37 gay and bisexual men from five Canadian provinces about stem cell donation. Dr. Fingrut and colleagues reported the findings in February in an abstract at the Transplantation & Cellular Therapy Meetings.

Most participants didn’t know they “are eligible to donate stem cells, with many confusing stem cell versus blood donor eligibility criteria,” the researchers reported. According to Dr. Fingrut, some of the men “felt they were treated as second-class citizens, and that translated into frustration and decreased motivation to donate. There were concerns that they would be treated as though they shouldn’t be there.”

Canada has allowed gay men to donate stem cells for at least 10 years, Dr. Fingrut said. In 2022, Canadian officials said blood banks would no longer require MSM donors to have been abstinent from sex for 3 months, the BBC reported. However, donors will be asked about high-risk sexual behaviors.

The United States, where HIV spread through the blood supply during the early years of the AIDS pandemic and killed thousands of hemophiliacs, has much been slower to change its policies. For decades, starting in the 1980s, both blood banks and stem cell donation programs chose to lower the risk by turning away MSM donors.

Policies only began to change in recent years. Be the Match’s registry led the way by welcoming MSM in 2015. Stem cell donations go through more extensive testing than blood donations, Dr. Adkins said, so it’s more likely that HIV will be screened out. Also, he said, officials probably realized “it was necessary to widen the donor pool in order to best serve the patients” because it’s so hard to find matched stem-cell donors.

Be the Match has also stepped up its outreach to the LGBTQ community. “During Pride Month in 2022, Be The Match sponsored booths at events in 12 major markets from coast to coast,” said Jamie Margolis, senior vice president of Donor Services. “These efforts enabled us to increase awareness among more than 500,000 festival attendees and added more than 2,000 new members to the Be The Match Registry. We also produced a social media awareness campaign featuring one of our own employees, who is a cofounder of the Pride Employee Resource Group at Be The Match and a recent blood stem cell donor.”

In 2020 as blood banks became desperate for donations during the early days of the COVID-19 pandemic, the FDA changed its policy and required MSM to be abstinent for 3 months instead of 1 year before giving blood. (Prior to December 2014, any man who’d had sex with a man, even once, was indefinitely banned from giving blood.)

The 3-month policy instituted in 2020 drew fire from critics such as the American Medical Association, which noted the regulation treated men differently if they had unprotected sex with a single man versus with multiple women.

Now, the FDA is proposing that it once again change the policy about blood donations: It is recommending that there be no special polices regarding MSM. “All prospective donors who report having a new sexual partner or more than one sexual partner and had anal sex in the past 3 months would be deferred from donation.”

Under the proposal, anyone who’s ever had HIV will not be able to donate. (They can’t donate stem cells either.) And the FDA proposes restrictions on those who take pre-exposure prophylaxis or postexposure prophylaxis for HIV.

Margolis, of Be the Match, noted that some members of the LGBTQ community may not be able to donate to Be The Match BioTherapies, which works with cell and gene therapy developers worldwide to provide cellular starting material. “These therapies may have different requirements than those for blood stem-cell transplants. Men who have had sex with men in the past 5 years or women who have had sex with a man who has had sex with a man in the past 5 years may not be able to donate to Be The Match BioTherapies. While we understand this could be upsetting or frustrating for someone who desires to be a part of these therapies, we are committed to following medical guidelines and regulations, while also advocating for our donors and the LBGTQIA+ community as a whole.”

MSM aren’t the only target of outreach by proponents of stem cell donation. In 2019, UT Southwestern’s Dr. Adkins and colleagues wrote a commentary in Bone Marrow Transplantation that called for bone marrow donation centers to do more to be welcoming to transgender donors. “The largest age group identifying as transgender is 18-24 years of life, which overlaps considerably with the population of hematopoietic stem cell donors, which tend to be younger individuals,” the researchers wrote.

The transgender community was “simply overlooked,” Dr. Adkins said. Since then, as he pointed out, things have changed. Now, Be the Match’s website notes that “members of the LGBTQIA+ community CAN join the registry and donate.” The organization says that “for medical reasons, everyone is asked to provide their sex assigned at birth when they register. Should you be called as a match, pronouns and gender identity are respected throughout the process.”

In addition, the site says people on prescription hormone therapy are not excluded from joining the registry. Patients who have undergone surgery within the last 12 months, including sex-reassignment procedures, “will be asked about the current status of their recovery and whether they are still seeing a physician for follow-up in regards to the surgery.”

What’s next? Dr. Fingrut said he expects the lifting of strict rules about MSM and blood donation will boost stem cell donation in the community.

There seems to be plenty of room for more outreach. Cole Williams, founder of Pride & Plasma, which advocates for allowing gay men to give blood, suggested in an interview that advocates who want to increase stem cell donation in the LGBTQ community reach out to its community centers, health organizations, providers, and clinics.

So far, though, “I haven’t seen a big call for registration of any individuals unless they have a personal relation to bone marrow donation,” he said.

Dr. Fingrut and Dr. Adkins report no disclosures.

LGBTQ advocates across North America aim to boost stem cell donation by reminding community members they are welcome to give – and that gay men don’t face the same restrictions as they’ve faced, at least thus far, in donating blood.

In fact, gay men have been able to donate stem cells in the United States since 2015. That’s when National Marrow Donor Program’s Be the Match registry lifted restrictions on men who have sex with men (MSM).

Physicians say advocacy is still necessary, because LGBTQ people may assume they can’t donate or be wary of clinicians. “The LGBTQIA+ population in general has experienced a lot of issues with the medical-industrial complex in terms of discrimination and inappropriate care,” said UT Southwestern Medical Center pathologist Brian Adkins, MD, who manages the blood bank at Children’s Health in Dallas, in an interview. “There’s a weariness there that may produce some hesitancy to interact with the donation process.”

An estimated 6.8 million people give blood in the United States each year, and an estimated 9 million people are registered as potential stem cell donors. A total of 22,013 hematopoietic cell transplantation procedures were performed in 2020, according to the U.S. Health Resources and Services Administration.

Expanding the number of LGBTQ donors, especially those born as biological males, could pay major dividends. As Dr. Adkins noted, the ideal stem cell donor is young – Be the Match says doctors generally prefer donors aged 18-35 – and male. According to a 2021 Gallup Poll, 21% of those born from 1997 to 2003 (Generation Z) say they’re LGBTQ, as do 11% of those born from 1981 to 1996 (Millennials).

In North America, the most extensive outreach to the LGBTQ community about stem cell donation has been launched in Canada. There, an organization called Stem Cell Club focuses on encouraging college students and other young people to register as potential stem cell donors.

Stem Cell Club has several campaigns aimed at ethnic minority groups, and its Saving Lives With Pride project focuses on MSM. The project’s web page includes testimonials from a woman whose life was saved by an unrelated gay male donor and from a gay male nurse who recovered from blood cancer thanks to a stem cell donation. The site also includes videos about stem cell donation featuring LGBTQ young people and Canadian hematologists.

“Our specialized collection center will treat donors with the highest levels of respect and courtesy, indeed as heroes of their unselfish gift that can truly save a life,” says Ottawa Hospital transplant hematologist David Allan, MD, in one of the videos.

Stem Cell Club was founded by transplant hematologist Warren Fingrut, MD, a research fellow at Memorial Sloan Kettering Cancer Center. In an interview, he said the organization’s LGBTQ project has promoted stem cell donation at several annual gay pride events and will continue the outreach this coming summer. In 2018 and 2019, advocates recruited 354 potential stem-cell donors (40% male, 42 non-White) at five pride events, Dr. Fingrut and colleagues reported last year in the journal Bone Marrow Transplantation.

For a new study, researchers interviewed 37 gay and bisexual men from five Canadian provinces about stem cell donation. Dr. Fingrut and colleagues reported the findings in February in an abstract at the Transplantation & Cellular Therapy Meetings.

Most participants didn’t know they “are eligible to donate stem cells, with many confusing stem cell versus blood donor eligibility criteria,” the researchers reported. According to Dr. Fingrut, some of the men “felt they were treated as second-class citizens, and that translated into frustration and decreased motivation to donate. There were concerns that they would be treated as though they shouldn’t be there.”

Canada has allowed gay men to donate stem cells for at least 10 years, Dr. Fingrut said. In 2022, Canadian officials said blood banks would no longer require MSM donors to have been abstinent from sex for 3 months, the BBC reported. However, donors will be asked about high-risk sexual behaviors.

The United States, where HIV spread through the blood supply during the early years of the AIDS pandemic and killed thousands of hemophiliacs, has much been slower to change its policies. For decades, starting in the 1980s, both blood banks and stem cell donation programs chose to lower the risk by turning away MSM donors.

Policies only began to change in recent years. Be the Match’s registry led the way by welcoming MSM in 2015. Stem cell donations go through more extensive testing than blood donations, Dr. Adkins said, so it’s more likely that HIV will be screened out. Also, he said, officials probably realized “it was necessary to widen the donor pool in order to best serve the patients” because it’s so hard to find matched stem-cell donors.

Be the Match has also stepped up its outreach to the LGBTQ community. “During Pride Month in 2022, Be The Match sponsored booths at events in 12 major markets from coast to coast,” said Jamie Margolis, senior vice president of Donor Services. “These efforts enabled us to increase awareness among more than 500,000 festival attendees and added more than 2,000 new members to the Be The Match Registry. We also produced a social media awareness campaign featuring one of our own employees, who is a cofounder of the Pride Employee Resource Group at Be The Match and a recent blood stem cell donor.”

In 2020 as blood banks became desperate for donations during the early days of the COVID-19 pandemic, the FDA changed its policy and required MSM to be abstinent for 3 months instead of 1 year before giving blood. (Prior to December 2014, any man who’d had sex with a man, even once, was indefinitely banned from giving blood.)

The 3-month policy instituted in 2020 drew fire from critics such as the American Medical Association, which noted the regulation treated men differently if they had unprotected sex with a single man versus with multiple women.

Now, the FDA is proposing that it once again change the policy about blood donations: It is recommending that there be no special polices regarding MSM. “All prospective donors who report having a new sexual partner or more than one sexual partner and had anal sex in the past 3 months would be deferred from donation.”

Under the proposal, anyone who’s ever had HIV will not be able to donate. (They can’t donate stem cells either.) And the FDA proposes restrictions on those who take pre-exposure prophylaxis or postexposure prophylaxis for HIV.

Margolis, of Be the Match, noted that some members of the LGBTQ community may not be able to donate to Be The Match BioTherapies, which works with cell and gene therapy developers worldwide to provide cellular starting material. “These therapies may have different requirements than those for blood stem-cell transplants. Men who have had sex with men in the past 5 years or women who have had sex with a man who has had sex with a man in the past 5 years may not be able to donate to Be The Match BioTherapies. While we understand this could be upsetting or frustrating for someone who desires to be a part of these therapies, we are committed to following medical guidelines and regulations, while also advocating for our donors and the LBGTQIA+ community as a whole.”

MSM aren’t the only target of outreach by proponents of stem cell donation. In 2019, UT Southwestern’s Dr. Adkins and colleagues wrote a commentary in Bone Marrow Transplantation that called for bone marrow donation centers to do more to be welcoming to transgender donors. “The largest age group identifying as transgender is 18-24 years of life, which overlaps considerably with the population of hematopoietic stem cell donors, which tend to be younger individuals,” the researchers wrote.

The transgender community was “simply overlooked,” Dr. Adkins said. Since then, as he pointed out, things have changed. Now, Be the Match’s website notes that “members of the LGBTQIA+ community CAN join the registry and donate.” The organization says that “for medical reasons, everyone is asked to provide their sex assigned at birth when they register. Should you be called as a match, pronouns and gender identity are respected throughout the process.”

In addition, the site says people on prescription hormone therapy are not excluded from joining the registry. Patients who have undergone surgery within the last 12 months, including sex-reassignment procedures, “will be asked about the current status of their recovery and whether they are still seeing a physician for follow-up in regards to the surgery.”

What’s next? Dr. Fingrut said he expects the lifting of strict rules about MSM and blood donation will boost stem cell donation in the community.

There seems to be plenty of room for more outreach. Cole Williams, founder of Pride & Plasma, which advocates for allowing gay men to give blood, suggested in an interview that advocates who want to increase stem cell donation in the LGBTQ community reach out to its community centers, health organizations, providers, and clinics.

So far, though, “I haven’t seen a big call for registration of any individuals unless they have a personal relation to bone marrow donation,” he said.

Dr. Fingrut and Dr. Adkins report no disclosures.

LGBTQ advocates across North America aim to boost stem cell donation by reminding community members they are welcome to give – and that gay men don’t face the same restrictions as they’ve faced, at least thus far, in donating blood.

In fact, gay men have been able to donate stem cells in the United States since 2015. That’s when National Marrow Donor Program’s Be the Match registry lifted restrictions on men who have sex with men (MSM).

Physicians say advocacy is still necessary, because LGBTQ people may assume they can’t donate or be wary of clinicians. “The LGBTQIA+ population in general has experienced a lot of issues with the medical-industrial complex in terms of discrimination and inappropriate care,” said UT Southwestern Medical Center pathologist Brian Adkins, MD, who manages the blood bank at Children’s Health in Dallas, in an interview. “There’s a weariness there that may produce some hesitancy to interact with the donation process.”

An estimated 6.8 million people give blood in the United States each year, and an estimated 9 million people are registered as potential stem cell donors. A total of 22,013 hematopoietic cell transplantation procedures were performed in 2020, according to the U.S. Health Resources and Services Administration.

Expanding the number of LGBTQ donors, especially those born as biological males, could pay major dividends. As Dr. Adkins noted, the ideal stem cell donor is young – Be the Match says doctors generally prefer donors aged 18-35 – and male. According to a 2021 Gallup Poll, 21% of those born from 1997 to 2003 (Generation Z) say they’re LGBTQ, as do 11% of those born from 1981 to 1996 (Millennials).

In North America, the most extensive outreach to the LGBTQ community about stem cell donation has been launched in Canada. There, an organization called Stem Cell Club focuses on encouraging college students and other young people to register as potential stem cell donors.

Stem Cell Club has several campaigns aimed at ethnic minority groups, and its Saving Lives With Pride project focuses on MSM. The project’s web page includes testimonials from a woman whose life was saved by an unrelated gay male donor and from a gay male nurse who recovered from blood cancer thanks to a stem cell donation. The site also includes videos about stem cell donation featuring LGBTQ young people and Canadian hematologists.

“Our specialized collection center will treat donors with the highest levels of respect and courtesy, indeed as heroes of their unselfish gift that can truly save a life,” says Ottawa Hospital transplant hematologist David Allan, MD, in one of the videos.

Stem Cell Club was founded by transplant hematologist Warren Fingrut, MD, a research fellow at Memorial Sloan Kettering Cancer Center. In an interview, he said the organization’s LGBTQ project has promoted stem cell donation at several annual gay pride events and will continue the outreach this coming summer. In 2018 and 2019, advocates recruited 354 potential stem-cell donors (40% male, 42 non-White) at five pride events, Dr. Fingrut and colleagues reported last year in the journal Bone Marrow Transplantation.

For a new study, researchers interviewed 37 gay and bisexual men from five Canadian provinces about stem cell donation. Dr. Fingrut and colleagues reported the findings in February in an abstract at the Transplantation & Cellular Therapy Meetings.

Most participants didn’t know they “are eligible to donate stem cells, with many confusing stem cell versus blood donor eligibility criteria,” the researchers reported. According to Dr. Fingrut, some of the men “felt they were treated as second-class citizens, and that translated into frustration and decreased motivation to donate. There were concerns that they would be treated as though they shouldn’t be there.”

Canada has allowed gay men to donate stem cells for at least 10 years, Dr. Fingrut said. In 2022, Canadian officials said blood banks would no longer require MSM donors to have been abstinent from sex for 3 months, the BBC reported. However, donors will be asked about high-risk sexual behaviors.

The United States, where HIV spread through the blood supply during the early years of the AIDS pandemic and killed thousands of hemophiliacs, has much been slower to change its policies. For decades, starting in the 1980s, both blood banks and stem cell donation programs chose to lower the risk by turning away MSM donors.

Policies only began to change in recent years. Be the Match’s registry led the way by welcoming MSM in 2015. Stem cell donations go through more extensive testing than blood donations, Dr. Adkins said, so it’s more likely that HIV will be screened out. Also, he said, officials probably realized “it was necessary to widen the donor pool in order to best serve the patients” because it’s so hard to find matched stem-cell donors.

Be the Match has also stepped up its outreach to the LGBTQ community. “During Pride Month in 2022, Be The Match sponsored booths at events in 12 major markets from coast to coast,” said Jamie Margolis, senior vice president of Donor Services. “These efforts enabled us to increase awareness among more than 500,000 festival attendees and added more than 2,000 new members to the Be The Match Registry. We also produced a social media awareness campaign featuring one of our own employees, who is a cofounder of the Pride Employee Resource Group at Be The Match and a recent blood stem cell donor.”

In 2020 as blood banks became desperate for donations during the early days of the COVID-19 pandemic, the FDA changed its policy and required MSM to be abstinent for 3 months instead of 1 year before giving blood. (Prior to December 2014, any man who’d had sex with a man, even once, was indefinitely banned from giving blood.)

The 3-month policy instituted in 2020 drew fire from critics such as the American Medical Association, which noted the regulation treated men differently if they had unprotected sex with a single man versus with multiple women.

Now, the FDA is proposing that it once again change the policy about blood donations: It is recommending that there be no special polices regarding MSM. “All prospective donors who report having a new sexual partner or more than one sexual partner and had anal sex in the past 3 months would be deferred from donation.”

Under the proposal, anyone who’s ever had HIV will not be able to donate. (They can’t donate stem cells either.) And the FDA proposes restrictions on those who take pre-exposure prophylaxis or postexposure prophylaxis for HIV.

Margolis, of Be the Match, noted that some members of the LGBTQ community may not be able to donate to Be The Match BioTherapies, which works with cell and gene therapy developers worldwide to provide cellular starting material. “These therapies may have different requirements than those for blood stem-cell transplants. Men who have had sex with men in the past 5 years or women who have had sex with a man who has had sex with a man in the past 5 years may not be able to donate to Be The Match BioTherapies. While we understand this could be upsetting or frustrating for someone who desires to be a part of these therapies, we are committed to following medical guidelines and regulations, while also advocating for our donors and the LBGTQIA+ community as a whole.”

MSM aren’t the only target of outreach by proponents of stem cell donation. In 2019, UT Southwestern’s Dr. Adkins and colleagues wrote a commentary in Bone Marrow Transplantation that called for bone marrow donation centers to do more to be welcoming to transgender donors. “The largest age group identifying as transgender is 18-24 years of life, which overlaps considerably with the population of hematopoietic stem cell donors, which tend to be younger individuals,” the researchers wrote.

The transgender community was “simply overlooked,” Dr. Adkins said. Since then, as he pointed out, things have changed. Now, Be the Match’s website notes that “members of the LGBTQIA+ community CAN join the registry and donate.” The organization says that “for medical reasons, everyone is asked to provide their sex assigned at birth when they register. Should you be called as a match, pronouns and gender identity are respected throughout the process.”

In addition, the site says people on prescription hormone therapy are not excluded from joining the registry. Patients who have undergone surgery within the last 12 months, including sex-reassignment procedures, “will be asked about the current status of their recovery and whether they are still seeing a physician for follow-up in regards to the surgery.”

What’s next? Dr. Fingrut said he expects the lifting of strict rules about MSM and blood donation will boost stem cell donation in the community.

There seems to be plenty of room for more outreach. Cole Williams, founder of Pride & Plasma, which advocates for allowing gay men to give blood, suggested in an interview that advocates who want to increase stem cell donation in the LGBTQ community reach out to its community centers, health organizations, providers, and clinics.

So far, though, “I haven’t seen a big call for registration of any individuals unless they have a personal relation to bone marrow donation,” he said.

Dr. Fingrut and Dr. Adkins report no disclosures.

The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.

The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.

These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.

In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.

“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.  
 

Upward trends in both diabetes types

Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.

The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.

The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.

For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).

Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).

The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.

And, the editorialists note, obesity is also a risk factor for type 1 diabetes. 

Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.

Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.

The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”

“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”

The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.

A version of this article originally appeared on Medscape.com.

The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.

The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.

These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.

In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.

“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.  
 

Upward trends in both diabetes types

Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.

The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.

The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.

For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).

Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).

The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.

And, the editorialists note, obesity is also a risk factor for type 1 diabetes. 

Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.

Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.

The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”

“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”

The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.

A version of this article originally appeared on Medscape.com.

The incidence of type 1 and type 2 diabetes continues to rise among children and adolescents in the United States, new data from the SEARCH for Diabetes in Youth study show.

The SEARCH data demonstrate an increase in the youth population aged 0-19 diagnosed with type 1 or type 2 diabetes in five representative U.S. centers. Between 2002 and 2018, the annual incidence rose by about 2% per year for type 1 diabetes and 5% per year for type 2 diabetes. The rates of increase for both types were greater among non-White than White youth.

These increases “will result in an expanding population of young adults at risk of developing early complications of diabetes whose health care needs will exceed those of their peers,” write Lynne E. Wagenknecht, DrPH, of Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues in their article, recently published in The Lancet Diabetes & Endocrinology.

In an accompanying editorial, Jonathan E. Shaw, MD, and Dianna J. Magliano, PhD, both at the Baker Heart and Diabetes Institute, Melbourne, write that one of the most “concerning findings” was a 7%-9% annual increase in the incidence of type 2 diabetes among Hispanic, Asian, and Pacific Islander populations.

“This is a health care crisis in the making. ...Youth and young-adult-onset type 2 diabetes are growing problems leading to poor outcomes and to widening social inequality, adversely affecting a population that might already be disadvantaged. Better information about its natural history, prevention, and management is urgently needed,” they write.  
 

Upward trends in both diabetes types

Overall, 18,169 children and adolescents with type 1 diabetes and 5,293 with type 2 diabetes were identified over the 17-year study period in SEARCH. After adjustment for age, sex, and race/ethnicity, there was a significant increase in type 1 diabetes incidence from 19.5 cases/100,000 population in 2002-2003 to 22.2/100,000 in 2017-2018, a 2.02% annual increase.

The upward trend was even greater for type 2 diabetes, from 9.0/100,000 in 2002-2003 to 17.9/100,000 in 2017-2018, a 5.31% annual increase.

The annual rate of increase in type 1 diabetes was highest among Asian/Pacific Islander youth (4.84%), followed by Hispanic (4.14%) and Black youth (2.93%): All significantly rose over the 17 years.

For type 2 diabetes, significant annual rates of increase were also highest for Asian/Pacific Islanders (8.92%), followed by Hispanic (7.17%) and Black youth (5.99%).

Among youth aged 15-19 years, the overall incidence of type 2 diabetes exceeded that of type 1 diabetes (19.7 vs. 14.6/100,000).

The incidence of type 2 diabetes may be rising because of increased rates of obesity, as well as increased screening of at-risk youth, the authors say.

And, the editorialists note, obesity is also a risk factor for type 1 diabetes. 

Peak incidence of type 1 diabetes occurred at age 10 years, while for type 2 diabetes, the peak was at 16 years. There were also seasonal peaks, occurring in January for type 1 diabetes and in August for type 2 diabetes. Those seasonal patterns have been previously reported; they are possibly because of increased viral infections and decreased sun exposure for the former, and increased physical exams in preparation for school in the latter, the authors speculate.

Dr. Shaw and Dr. Magliano note that the reduced incidence after age 16 years “might simply reflect a failure to diagnose,” suggesting that there will likely be an upturn in incidence in the subsequent decade.

The editorialists also point out: “Not only does the long duration of diabetes that youth-onset leads to cause a large burden of fatal and nonfatal complications, but it magnifies intergenerational effects.”

“When type 2 diabetes is already present before pregnancy, birth outcomes are worse, and the long-term metabolic health of the offspring is adversely affected. This does not bode well for the epidemic of diabetes and its complications.”

The study was funded by the Centers for Disease Control and Prevention and National Institutes of Health. The authors and Dr. Magliano have reported no relevant financial relationships. Dr. Shaw has reported receiving honoraria for lectures and for advisory boards and grants from AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Sanofi, Roche, Mylan, and Zuellig Pharma.

A version of this article originally appeared on Medscape.com.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

Low serum levels of the hepatitis B core-related antigen (HBcrAg) could be an early biomarker of a functional cure of a hepatitis B infection, according to new findings from a retrospective study.

A drop in HBcrAg predicted the seroclearance of hepatitis B surface antigen (HBsAg), the widely accepted measure of optimal liver-related outcomes in patient care and clinical trials, long before HBsAg levels actually fell.

“In a large retrospective cohort study of chronic hepatitis B patients, we found lower levels of HBcrAg were associated with higher probability of clearing HBsAg,” wrote Tai-Chung Tseng and coauthors at National Taiwan University Hospital in Taipei. “Reduction of HBcrAg developed 10 years before decline of HBsAg in patients with high HBsAg levels at baseline.”

Nearly 300 million people worldwide are estimated to be positive for the HBsAg antigen, a marker of active hepatitis B virus (HBV) infection. Chronic HBV puts individuals at greater risk of cirrhosis, hepatocellular carcinoma (HCC), and other liver complications.

Seroclearance of HBsAg is generally regarded as signaling a functional cure, because it is associated with low viral activity and good clinical outcomes. Patients with low HBsAg levels may transition to complete clearance, while those with levels of 1,000 IU/mL or higher rarely achieve clearance either spontaneously or through treatment.

As with HBsAg, higher serum levels of HBcrAg have been linked to a raised risk of adverse events, including increased viral activity and heightened risk of developing hepatitis B e antigen-negative hepatitis, cirrhosis, and HCC. Lower HBcrAg levels are associated with a greater likelihood of HBsAg seroclearance in chronic hepatitis B patients who discontinued antiviral therapy.

In a study published in Gastroenterology, researchers conducted a retrospective Taiwanese cohort study of 2,614 untreated patients with hepatitis B who underwent long-term follow-up at National Taiwan University Hospital. The median age was 38.2 years, and 60.6% were men. At baseline, 14.8% had HBsAg levels of less than 100 IU/mL, and 47.7% had HBcrAg levels less than 10,000 IU/mL. Most (77.5%) were infected with HBV genotype B. From stored serum samples, the researchers quantified levels of HBV DNA, HBsAg, and HBcrAg and evaluated the relationships with spontaneous HBsAg seroclearance.

Over an average follow-up of about 12 years, 465 patients cleared HBsAg, an incidence of 1.43% per year. Researchers stratified patients by levels of viral markers. Compared to those with the highest HBcrAg levels (> 100,000 IU/mL), lower levels of HBcrAg were associated with greater likelihood of HBsAg clearance.

Specifically, intermediate levels (10,000-99,999 IU/mL) were associated with nearly double the chance of HBsAg clearance (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.44-2.65), and the lowest levels (< 10,000 IU/mL) were associated with just over triple the chance of clearance (HR, 3.15; 95% CI, 2.45-4.05). These associations held up with multivariable analyses, and HBV DNA levels were not significantly associated with HBsAg clearance.

“Not surprisingly, HBsAg levels still serve as a better predictor than the other two biomarkers,” the authors wrote. “Notably, the HBsAg levels are more like a short-term predictor” (within 5 years).

For patients with higher HBsAg levels (> 1,000 IU/mL), it took a median of 16 years to achieve HBsAg clearance. A subanalysis of the 1,539 patients with HbsAg levels > 1,000 IU/mL found that only HBcrAg levels below 10,000 IU/mL predicted HBsAg seroclearance versus 100,000 U/mL or higher (adjusted HR, 1.95; 95% CI, 1.16-3.27).

HBsAg levels began to decline later, often between 5 and 9 years before HBsAg seroclearance occurs. However, HBcrAg levels became undetectable 10-14 years before HBsAg seroclearance. Among patients achieving undetectable levels of HBcrAg, the annual HBsAg seroclearance rate was higher in the second decade of follow-up than in the first decade (3.75% versus 0.97%).

HBcrAg levels reflect the transcriptional activity of covalently closed circular DNA (cccDNA), the authors noted, while HBsAg can come from cccDNA and HBV-DNA integrated into the host genome. Several novel hepatitis B therapies in development target cccDNA transcription, but it isn’t known if the strategy will result in HBsAg clearance.

In the discussion section, the authors speculated about the possible pathology and treatment implications for several chronic hepatitis B scenarios. For example, the finding that HBcrAg clearance usually precedes HBsAg clearance suggests that reduction of cccDNA transcription is a requirement for curing hepatitis B, the authors speculate, but it also suggests that add-on treatment may need to target HBsAg transcribed from the integrated viral genome for a functional cure.

The researchers noted several study limitations, including that the cohort included only Asians largely with HBV genotypes B or C and that “further validation from Caucasian patients infected with genotypes types A or D is mandatory.”

Tai-Chung Tseng disclosed financial conflicts with Fujirebio, Bristol-Myers Squibb, and Gilead Sciences. The remaining authors had no conflicts of interest. The study received grant support from several institutions, including National Taiwan University Hospital.

SAN DIEGO – As mounting evidence points to the benefits of physical activity for patients with multiple sclerosis (MS), researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.

A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.

“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.

Preliminary work showed that use of the app was associated with a 31% increase in physical activity.

They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Higher levels of depression and fatigue

Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.

With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.

Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”

As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.

Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”

The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.

But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”

With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.

However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
 

Clear structural effects

Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.

As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.

However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.

It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.

The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.

“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.

Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.

“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”

While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.

“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.

She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.

Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
 

Improved mood, cognition, pain, sleep

In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.

“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”

However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”

The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – As mounting evidence points to the benefits of physical activity for patients with multiple sclerosis (MS), researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.

A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.

“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.

Preliminary work showed that use of the app was associated with a 31% increase in physical activity.

They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Higher levels of depression and fatigue

Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.

With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.

Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”

As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.

Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”

The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.

But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”

With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.

However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
 

Clear structural effects

Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.

As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.

However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.

It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.

The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.

“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.

Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.

“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”

While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.

“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.

She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.

Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
 

Improved mood, cognition, pain, sleep

In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.

“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”

However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”

The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – As mounting evidence points to the benefits of physical activity for patients with multiple sclerosis (MS), researchers have developed a mobile app to encourage young patients with the disease to become more active. The smartphone-based app provides tailored physical activity information, coaching advice, and tools to increase social connectedness.

A pilot study examining whether the intervention changes activity, depression, and fatigue levels should be wrapped up later this year, but it looks as though the app is succeeding.

“The feedback we’ve gotten so far from our coaches is that the kids seem highly motivated,” said one of the creators, E. Ann Yeh, MD, professor in the faculty of medicine at the University of Toronto and director of the pediatric MS and neuroinflammatory disorders program at the Hospital for Sick Children.

Preliminary work showed that use of the app was associated with a 31% increase in physical activity.

They discussed this and other studies of the role of exercise in MS at the annual meeting of the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Higher levels of depression and fatigue

Studies show that youths with MS who are less physically active are more likely to experience higher levels of fatigue and depression. Evidence suggests just 15-30 more minutes of moderate to vigorous physical activity (MVPA) makes a clinical difference in terms of improved depression and fatigue scores, said Dr. Yeh.

With moderate physical activity (for example, a brisk walk or raking the yard), the maximal heart rate (HRmax) reaches 64%-76%, while with vigorous physical activity (which includes jogging/running or participating in a strenuous fitness class), the HRmax reaches 77%-93%.

Dr. Yeh described vigorous physical activity as “the stuff that makes you sweat, makes your heart rate go up, and makes you not be able to talk when you’re moving.”

As it stands, kids get very little MVPA – 9.5 min/day, which is well below the recommended 60 min/day. Adults do a bit better – 18.7 min/day of MVPA – but this is still below the recommended 30 min/day.

Being physically active improves fatigue for adults as well as kids, said Dr. Yeh. She referred to a network meta-analysis of 27 studies involving 1,470 participants that evaluated 10 types of exercise interventions, including yoga, resistance training, dance, and aquatic activities. It found that exercise “does move the needle,” she said. “Regardless of the kind of activity that was studied, fatigue seemed to improve.”

The authors of that study ranked aquatic exercise as the most effective intervention. “It’s possible that aquatics worked better because people who can’t move well feel more comfortable in the water,” Dr. Yeh said.

But she cautioned that the one study in the meta-analysis that found a “quite strong” effect of aquatic exercise was “very small.”

With regard to depression, which affects about 30% of people with MS, Dr. Yeh told meeting attendees, “unfortunately, the data are less clear” when it comes to physical activity for adults. One meta-analysis of 15 randomized controlled trials involving 331 exercising participants and 260 control persons found that only a few studies showed positive effects of exercise on depressive symptoms.

However, Dr. Yeh noted that in this review, the baseline depressive symptoms of participants were “above the cutoff level,” which makes it more difficult to demonstrate change in depression levels.
 

Clear structural effects

Researchers have also described clear brain structural and functional effects from being physically active. For example, MVPA has been shown to affect brain volume, and it has been associated with better optical coherence tomography (OCT) metrics, which measures retinal thinning.

As for the impact of exercise on memory deficits, which is of interest, given the current focus on Alzheimer’s disease, “the jury is still out,” said Dr. Yeh. One 24-week randomized controlled trial found no difference in results on the Brief Repeatable Battery of Neuropsychological tests between participants who engaged in progressive aerobic exercise and control persons.

However, said Dr. Yeh, “the problem may not be with the intervention but with the outcome measures” and potentially with the populations studied.

It might be a different story for high-intensity exercise, though. A study by Danish researchers assessed the effects of a 24-week high-intensity intervention among 84 adult patients with mild-severe impairment.

The primary outcome of that study, which was the percentage of brain volume change, was not met, possibly because the study was too short. There were significant results for some secondary endpoints, including improved cardiorespiratory fitness and lower relapse rate.

“Even though on the face of it, it sounds like a negative study, there were important outcomes,” said Dr. Yeh.

Research into the possible mechanisms behind positive effects of physical activity is limited with regard to patients with MS, said Dr. Yeh. Some studies have implicated certain circulating factors, such as the cytokine irisin and brain-derived neurotrophic factor, but more work is needed, she said.

“There is need for further mechanistic knowledge related to exercise in MS, and this must be accomplished through prospective, randomized studies.”

While exercise likely makes some difference for MS patients, the problem is in getting them to be more active. “You can’t just write a prescription,” said Dr. Yeh.

“Patients should be doing whatever they can, but gradually, and should not go crazy at the beginning because they’ll just burn out,” she said.

She stressed that patients need to find what works for them personally. It’s also important for them to find ways to be active with a friend who can be “a motivator” to help sustain physical activity goals, said Dr. Yeh.

Patients can also look online for remote physical activity programs geared to people with MS, which popped up during the pandemic.
 

Improved mood, cognition, pain, sleep

In a comment, Marwa Kaisey, MD, assistant professor of neurology at Cedars-Sinai Medical Center, in Los Angeles, who cochaired the session highlighting the presentation, praised Dr. Yeh’s “excellent talk,” which highlighted the “strong benefit” of exercise for patients with MS.

“As a clinician, I often talk to my patients about the importance of physical exercise and have heard countless anecdotes of how their workout programs helped improve mood, cognition, pain, or sleep.”

However, she agreed there are several areas “where we need more data-driven solutions and a mechanistic understanding of the benefits of physical exercise.”

The pilot study was funded by the Consortium of Multiple Sclerosis Centers. The MS Society of Canada funded early work on the app, and the National MS Society is funding the trial of the app. Dr. Yeh receives support from the MS Society of Canada. Dr. Kaisey reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research may help physicians avoid the widespread problem of antipsychotic-induced weight gain and changes in metabolic parameters in patients with acute schizophrenia.

In the first dose-response meta-analysis focusing on antipsychotic-induced weight gain, researchers provide data on the trajectory of this risk associated with individual agents.

Investigators analyzed 52 randomized controlled trials (RCTs) encompassing more than 22,500 participants with schizophrenia treated with antipsychotics. They found that, with the exception of aripiprazole long-acting injectable (LAI), all of the other antipsychotics has significant dose-response effect on weight gain. Furthermore, weight gain occurred with some antipsychotics even at relatively low doses.  

“We found significant dose-response associations for weight and metabolic variables, with a unique signature for each antipsychotic,” write the investigators, led by Michel Sabé, MD, of the division of adult psychiatry, department of psychiatry, Geneva University Hospitals.

“Despite several limitations, including the limited number of available studies, our results may provide useful information for preventing weight gain and metabolic disturbances by adapting antipsychotic doses,” they add.

The study was published online in The Journal of Clinical Psychiatry.
 

Balancing risks and benefits

Antipsychotics are first-line therapy for schizophrenia and are associated with weight gain, lipid disturbances, and glucose dysregulation – especially second-generation antipsychotics (SGAs), which can lead to obesity, type 2 diabetes, and metabolic syndrome.

Given that people with schizophrenia also tend to have lifestyle-related cardiovascular risk factors, it’s important to find “a balance between beneficial and adverse effects of antipsychotics,” the investigators note

The question of whether weight gain and metabolic dysregulation are dose-dependent “remains controversial.” The effect of specific SGAs on weight gain has been investigated, but only one study has been conducted using a dose-response meta-analysis, and that study did not address metabolic disturbance.

The investigators conducted a systematic review and a dose-response meta-analysis of fixed-dose randomized controlled trials (RCTs) investigating antipsychotic-induced weight gain and metabolic disturbance in adults with acute schizophrenia.

To be included in the analysis, RCTs had to focus on adult patients with schizophrenia or related disorders and include a placebo as a comparator to the drug.

Studies involved only short-term administration of antipsychotics (2-13 weeks) rather than maintenance therapy.

The mean (SD) change in weight (body weight and/or body mass index) between baseline and the study endpoint constituted the primary outcome, with secondary outcomes including changes in metabolic parameters.

The researchers characterized the dose-response relationship using a nonlinear restricted cubic spline model, with three “knots” located at the 10th, 50th, and 90th percentiles of overall dose distribution.

They also calculated dose-response curves and estimated 50% and 95% effective doses (ED50 and ED95, respectively), extracted from the estimated dose-response curves for each antipsychotic.

The researchers then calculated the weight gain at each effective dose (ED50 and ED95) in milligrams and the weight gain corresponding to the ED95 value in kilograms.
 

Shared decision-making

Of 6,812 citations, the researchers selected 52 RCTs that met inclusion criteria (n = 22,588 participants, with 16,311 receiving antipsychotics and 6,277 receiving placebo; mean age, 38.5 years, 69.2% male). The studies were conducted between1996 and 2021.

The risk for bias in most studies was “low,” although 21% of the studies “presented a high risk.”

With the exception of aripiprazole LAI, all of the other antipsychotics had a “significant dose-response” association with weight.

For example, oral aripiprazole exhibited a significant dose-response association for weight, but there was no significant association found for aripiprazole LAI (c2 = 8.744; P = .0126 vs. c2 = 3.107; P = .2115). However, both curves were still ascending at maximum doses, the authors note.

Metabolically neutral

Antipsychotics with a decreasing or quasi-parabolic dose-response curve for weight included brexpiprazole, cariprazine, haloperidol, lurasidone, and quetiapine ER: for these antipsychotics, the ED95 weight gain ranged from 0.53 kg to 1.40 kg.

These antipsychotics “reach their weight gain ED95 at relatively low median effective doses, and higher doses, which mostly correspond to near-maximum effective doses, may even be associated with less weight gain,” the authors note.

In addition, only doses higher than the near-maximum effective dose of brexpiprazole were associated with a small increase in total cholesterol. And cariprazine presented “significantly decreasing curves” at higher doses for LDL cholesterol.

With the exception of quetiapine, this group of medications might be regarded as “metabolically neutral” in terms of weight gain and metabolic disturbances.

Antipsychotics with a plateau-shaped curve were asenapine, iloperidone, paliperidone LAI, quetiapine IR, and risperidone, with a weight gain ED95 ranging from 1.36 to 2.65 kg.

Aripiprazole and olanzapine (oral and LAI formulations), as well as risperidone LAI and oral paliperidone, presented weight gain curves that continued climbing at higher doses (especially olanzapine). However, the drugs have different metabolic profiles, ranging from 0.88 kg ED95 for oral aripiprazole to 4.29 kg for olanzapine LAI.

Olanzapine had the most pronounced weight gain, in addition to associations with all metabolic outcomes.

For some drugs with important metabolic side effects, “a lower dose might provide a better combination of high efficacy and reduced metabolic side effects,” the authors write.

The findings might “provide additional information for clinicians aiming to determine the most suitable dose to prevent weight gain and metabolic disturbance in a shared decision-making process with their patients,” they note.

The results add to “existing concerns about the use of olanzapine as a first-line drug,” they add.
 

Lowest effective dose

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said clinicians “not infrequently increase doses to achieve better symptom control, [but] this decision should be informed by the additional observation herein that the increase in those could be accompanied by weight increase.”

Moreover, many patients “take concomitant medications that could possibly increase the bioavailability of antipsychotics, which may also increase the risk for weight gain,” said Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto. He was not involved with this study.

“These data provide a reason to believe that for many people antipsychotic-associated weight gain could be mitigated by using the lowest effective dose, and rather than censor the use of some medications out of concern for weight gain, perhaps using the lowest effective dose of the medication will provide the opportunity for mitigation,” he added. “So I think it really guides clinicians to provide the lowest effective dose as a potential therapeutic and preventive strategy.”

The study received no financial support. Dr. Sabé reports no relevant financial relationships. Three coauthors report relationships with industry; the full list is contained in the original article.

Dr. McIntyre is a CEO of Braxia Scientific Corp. He has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences.

A version of this article first appeared on Medscape.com.

New research may help physicians avoid the widespread problem of antipsychotic-induced weight gain and changes in metabolic parameters in patients with acute schizophrenia.

In the first dose-response meta-analysis focusing on antipsychotic-induced weight gain, researchers provide data on the trajectory of this risk associated with individual agents.

Investigators analyzed 52 randomized controlled trials (RCTs) encompassing more than 22,500 participants with schizophrenia treated with antipsychotics. They found that, with the exception of aripiprazole long-acting injectable (LAI), all of the other antipsychotics has significant dose-response effect on weight gain. Furthermore, weight gain occurred with some antipsychotics even at relatively low doses.  

“We found significant dose-response associations for weight and metabolic variables, with a unique signature for each antipsychotic,” write the investigators, led by Michel Sabé, MD, of the division of adult psychiatry, department of psychiatry, Geneva University Hospitals.

“Despite several limitations, including the limited number of available studies, our results may provide useful information for preventing weight gain and metabolic disturbances by adapting antipsychotic doses,” they add.

The study was published online in The Journal of Clinical Psychiatry.
 

Balancing risks and benefits

Antipsychotics are first-line therapy for schizophrenia and are associated with weight gain, lipid disturbances, and glucose dysregulation – especially second-generation antipsychotics (SGAs), which can lead to obesity, type 2 diabetes, and metabolic syndrome.

Given that people with schizophrenia also tend to have lifestyle-related cardiovascular risk factors, it’s important to find “a balance between beneficial and adverse effects of antipsychotics,” the investigators note

The question of whether weight gain and metabolic dysregulation are dose-dependent “remains controversial.” The effect of specific SGAs on weight gain has been investigated, but only one study has been conducted using a dose-response meta-analysis, and that study did not address metabolic disturbance.

The investigators conducted a systematic review and a dose-response meta-analysis of fixed-dose randomized controlled trials (RCTs) investigating antipsychotic-induced weight gain and metabolic disturbance in adults with acute schizophrenia.

To be included in the analysis, RCTs had to focus on adult patients with schizophrenia or related disorders and include a placebo as a comparator to the drug.

Studies involved only short-term administration of antipsychotics (2-13 weeks) rather than maintenance therapy.

The mean (SD) change in weight (body weight and/or body mass index) between baseline and the study endpoint constituted the primary outcome, with secondary outcomes including changes in metabolic parameters.

The researchers characterized the dose-response relationship using a nonlinear restricted cubic spline model, with three “knots” located at the 10th, 50th, and 90th percentiles of overall dose distribution.

They also calculated dose-response curves and estimated 50% and 95% effective doses (ED50 and ED95, respectively), extracted from the estimated dose-response curves for each antipsychotic.

The researchers then calculated the weight gain at each effective dose (ED50 and ED95) in milligrams and the weight gain corresponding to the ED95 value in kilograms.
 

Shared decision-making

Of 6,812 citations, the researchers selected 52 RCTs that met inclusion criteria (n = 22,588 participants, with 16,311 receiving antipsychotics and 6,277 receiving placebo; mean age, 38.5 years, 69.2% male). The studies were conducted between1996 and 2021.

The risk for bias in most studies was “low,” although 21% of the studies “presented a high risk.”

With the exception of aripiprazole LAI, all of the other antipsychotics had a “significant dose-response” association with weight.

For example, oral aripiprazole exhibited a significant dose-response association for weight, but there was no significant association found for aripiprazole LAI (c2 = 8.744; P = .0126 vs. c2 = 3.107; P = .2115). However, both curves were still ascending at maximum doses, the authors note.

Metabolically neutral

Antipsychotics with a decreasing or quasi-parabolic dose-response curve for weight included brexpiprazole, cariprazine, haloperidol, lurasidone, and quetiapine ER: for these antipsychotics, the ED95 weight gain ranged from 0.53 kg to 1.40 kg.

These antipsychotics “reach their weight gain ED95 at relatively low median effective doses, and higher doses, which mostly correspond to near-maximum effective doses, may even be associated with less weight gain,” the authors note.

In addition, only doses higher than the near-maximum effective dose of brexpiprazole were associated with a small increase in total cholesterol. And cariprazine presented “significantly decreasing curves” at higher doses for LDL cholesterol.

With the exception of quetiapine, this group of medications might be regarded as “metabolically neutral” in terms of weight gain and metabolic disturbances.

Antipsychotics with a plateau-shaped curve were asenapine, iloperidone, paliperidone LAI, quetiapine IR, and risperidone, with a weight gain ED95 ranging from 1.36 to 2.65 kg.

Aripiprazole and olanzapine (oral and LAI formulations), as well as risperidone LAI and oral paliperidone, presented weight gain curves that continued climbing at higher doses (especially olanzapine). However, the drugs have different metabolic profiles, ranging from 0.88 kg ED95 for oral aripiprazole to 4.29 kg for olanzapine LAI.

Olanzapine had the most pronounced weight gain, in addition to associations with all metabolic outcomes.

For some drugs with important metabolic side effects, “a lower dose might provide a better combination of high efficacy and reduced metabolic side effects,” the authors write.

The findings might “provide additional information for clinicians aiming to determine the most suitable dose to prevent weight gain and metabolic disturbance in a shared decision-making process with their patients,” they note.

The results add to “existing concerns about the use of olanzapine as a first-line drug,” they add.
 

Lowest effective dose

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said clinicians “not infrequently increase doses to achieve better symptom control, [but] this decision should be informed by the additional observation herein that the increase in those could be accompanied by weight increase.”

Moreover, many patients “take concomitant medications that could possibly increase the bioavailability of antipsychotics, which may also increase the risk for weight gain,” said Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto. He was not involved with this study.

“These data provide a reason to believe that for many people antipsychotic-associated weight gain could be mitigated by using the lowest effective dose, and rather than censor the use of some medications out of concern for weight gain, perhaps using the lowest effective dose of the medication will provide the opportunity for mitigation,” he added. “So I think it really guides clinicians to provide the lowest effective dose as a potential therapeutic and preventive strategy.”

The study received no financial support. Dr. Sabé reports no relevant financial relationships. Three coauthors report relationships with industry; the full list is contained in the original article.

Dr. McIntyre is a CEO of Braxia Scientific Corp. He has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences.

A version of this article first appeared on Medscape.com.

New research may help physicians avoid the widespread problem of antipsychotic-induced weight gain and changes in metabolic parameters in patients with acute schizophrenia.

In the first dose-response meta-analysis focusing on antipsychotic-induced weight gain, researchers provide data on the trajectory of this risk associated with individual agents.

Investigators analyzed 52 randomized controlled trials (RCTs) encompassing more than 22,500 participants with schizophrenia treated with antipsychotics. They found that, with the exception of aripiprazole long-acting injectable (LAI), all of the other antipsychotics has significant dose-response effect on weight gain. Furthermore, weight gain occurred with some antipsychotics even at relatively low doses.  

“We found significant dose-response associations for weight and metabolic variables, with a unique signature for each antipsychotic,” write the investigators, led by Michel Sabé, MD, of the division of adult psychiatry, department of psychiatry, Geneva University Hospitals.

“Despite several limitations, including the limited number of available studies, our results may provide useful information for preventing weight gain and metabolic disturbances by adapting antipsychotic doses,” they add.

The study was published online in The Journal of Clinical Psychiatry.
 

Balancing risks and benefits

Antipsychotics are first-line therapy for schizophrenia and are associated with weight gain, lipid disturbances, and glucose dysregulation – especially second-generation antipsychotics (SGAs), which can lead to obesity, type 2 diabetes, and metabolic syndrome.

Given that people with schizophrenia also tend to have lifestyle-related cardiovascular risk factors, it’s important to find “a balance between beneficial and adverse effects of antipsychotics,” the investigators note

The question of whether weight gain and metabolic dysregulation are dose-dependent “remains controversial.” The effect of specific SGAs on weight gain has been investigated, but only one study has been conducted using a dose-response meta-analysis, and that study did not address metabolic disturbance.

The investigators conducted a systematic review and a dose-response meta-analysis of fixed-dose randomized controlled trials (RCTs) investigating antipsychotic-induced weight gain and metabolic disturbance in adults with acute schizophrenia.

To be included in the analysis, RCTs had to focus on adult patients with schizophrenia or related disorders and include a placebo as a comparator to the drug.

Studies involved only short-term administration of antipsychotics (2-13 weeks) rather than maintenance therapy.

The mean (SD) change in weight (body weight and/or body mass index) between baseline and the study endpoint constituted the primary outcome, with secondary outcomes including changes in metabolic parameters.

The researchers characterized the dose-response relationship using a nonlinear restricted cubic spline model, with three “knots” located at the 10th, 50th, and 90th percentiles of overall dose distribution.

They also calculated dose-response curves and estimated 50% and 95% effective doses (ED50 and ED95, respectively), extracted from the estimated dose-response curves for each antipsychotic.

The researchers then calculated the weight gain at each effective dose (ED50 and ED95) in milligrams and the weight gain corresponding to the ED95 value in kilograms.
 

Shared decision-making

Of 6,812 citations, the researchers selected 52 RCTs that met inclusion criteria (n = 22,588 participants, with 16,311 receiving antipsychotics and 6,277 receiving placebo; mean age, 38.5 years, 69.2% male). The studies were conducted between1996 and 2021.

The risk for bias in most studies was “low,” although 21% of the studies “presented a high risk.”

With the exception of aripiprazole LAI, all of the other antipsychotics had a “significant dose-response” association with weight.

For example, oral aripiprazole exhibited a significant dose-response association for weight, but there was no significant association found for aripiprazole LAI (c2 = 8.744; P = .0126 vs. c2 = 3.107; P = .2115). However, both curves were still ascending at maximum doses, the authors note.

Metabolically neutral

Antipsychotics with a decreasing or quasi-parabolic dose-response curve for weight included brexpiprazole, cariprazine, haloperidol, lurasidone, and quetiapine ER: for these antipsychotics, the ED95 weight gain ranged from 0.53 kg to 1.40 kg.

These antipsychotics “reach their weight gain ED95 at relatively low median effective doses, and higher doses, which mostly correspond to near-maximum effective doses, may even be associated with less weight gain,” the authors note.

In addition, only doses higher than the near-maximum effective dose of brexpiprazole were associated with a small increase in total cholesterol. And cariprazine presented “significantly decreasing curves” at higher doses for LDL cholesterol.

With the exception of quetiapine, this group of medications might be regarded as “metabolically neutral” in terms of weight gain and metabolic disturbances.

Antipsychotics with a plateau-shaped curve were asenapine, iloperidone, paliperidone LAI, quetiapine IR, and risperidone, with a weight gain ED95 ranging from 1.36 to 2.65 kg.

Aripiprazole and olanzapine (oral and LAI formulations), as well as risperidone LAI and oral paliperidone, presented weight gain curves that continued climbing at higher doses (especially olanzapine). However, the drugs have different metabolic profiles, ranging from 0.88 kg ED95 for oral aripiprazole to 4.29 kg for olanzapine LAI.

Olanzapine had the most pronounced weight gain, in addition to associations with all metabolic outcomes.

For some drugs with important metabolic side effects, “a lower dose might provide a better combination of high efficacy and reduced metabolic side effects,” the authors write.

The findings might “provide additional information for clinicians aiming to determine the most suitable dose to prevent weight gain and metabolic disturbance in a shared decision-making process with their patients,” they note.

The results add to “existing concerns about the use of olanzapine as a first-line drug,” they add.
 

Lowest effective dose

Commenting on the study, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, and head of the mood disorders psychopharmacology unit, said clinicians “not infrequently increase doses to achieve better symptom control, [but] this decision should be informed by the additional observation herein that the increase in those could be accompanied by weight increase.”

Moreover, many patients “take concomitant medications that could possibly increase the bioavailability of antipsychotics, which may also increase the risk for weight gain,” said Dr. McIntyre, chairman and executive director of the Brain and Cognitive Discover Foundation, Toronto. He was not involved with this study.

“These data provide a reason to believe that for many people antipsychotic-associated weight gain could be mitigated by using the lowest effective dose, and rather than censor the use of some medications out of concern for weight gain, perhaps using the lowest effective dose of the medication will provide the opportunity for mitigation,” he added. “So I think it really guides clinicians to provide the lowest effective dose as a potential therapeutic and preventive strategy.”

The study received no financial support. Dr. Sabé reports no relevant financial relationships. Three coauthors report relationships with industry; the full list is contained in the original article.

Dr. McIntyre is a CEO of Braxia Scientific Corp. He has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences.

A version of this article first appeared on Medscape.com.

Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.

The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.

The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.

Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.

“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.

“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented. 

“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.  

Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.

Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.

“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.

On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”

He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”

David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”

“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”

Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”

In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.

The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.  

The current 3-year results suggest the benefit appears to be maintained out for another year. 

The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).

In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.

Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.

Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.

However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.

On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.

Quality-of-life results looked good in both groups.

“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”

Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”

Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.

Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”

Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.

Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”

He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.

“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.    

Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.  

Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”

Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”

But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”

The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.

A version of this article first appeared on Medscape.com.

Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.

The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.

The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.

Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.

“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.

“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented. 

“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.  

Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.

Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.

“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.

On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”

He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”

David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”

“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”

Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”

In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.

The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.  

The current 3-year results suggest the benefit appears to be maintained out for another year. 

The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).

In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.

Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.

Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.

However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.

On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.

Quality-of-life results looked good in both groups.

“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”

Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”

Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.

Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”

Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.

Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”

He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.

“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.    

Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.  

Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”

Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”

But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”

The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.

A version of this article first appeared on Medscape.com.

Three-year results from the Evolut trial seem to provide more reassurance on the use of transcatheter aortic valve replacement (TAVR) in low-surgical-risk patients.

The 3-year results show that low-surgical-risk patients undergoing aortic valve replacement continue to show lower rates of all-cause mortality and disabling stroke with TAVR, compared with surgery.

The rates of all-cause mortality or disabling stroke (the primary endpoint) at 3 years were 7.4% with TAVR and 10.4% with surgery.

Rates of new pacemaker implantation continued to be higher after TAVR and the frequency of new onset atrial fibrillation was more common after surgery.

“At 3 years, the rate of all-cause mortality or disabling stroke after TAVR with the Evolut valve compared very favorably to surgery. The absolute difference between treatment arms remained consistent with a 30% relative reduction in the hazard of death or disabling stroke, with a P value that just missed statistical significance,” said Evolut investigator John Forrest, MD, Yale University School of Medicine, New Haven, Conn.

“The Kaplan-Meier curves show what we’ve come to expect – an early separation of the curves – but what’s unique here, and seen for the first time, is that the early separation is maintained at year 1 and year 2, and between years 2 and 3 the curve didn’t start to come together, but, if anything, separated a little,” Dr. Forrest commented. 

“Both components of the primary endpoint – all cause mortality and disabling stroke – numerically favor TAVR. The separation of the curves for stroke are maintained, and if anything, we see a further slight separation of the curves as we go forward out to 3 years in terms of all-cause mortality,” he added.  

Dr. Forrest presented the 3-year results from the Evolut trial at the joint scientific sessions of the American College of Cardiology and the World Heart Federation. They were simultaneously published online in the Journal of the American College of Cardiology.

Dr. Forrest also reported that TAVR patients continued to have better valve hemodynamics at 3 years and very low rates of valve thrombosis; moreover, rates of moderate or greater paravalvular regurgitation and paravalvular leak (factors that can affect valve durability) were also low, although mild paravalvular regurgitation was higher with TAVR.

“In these low-risk patients, the durability of the valve is going to be critically important,” Dr. Forrest commented. “The excellent valve performance and durable outcomes out to 3 years in low-risk patients affirms the role of TAVR in this population,” he concluded.

On how these results may affect clinical practice, Dr. Forrest said: “I think in the U.S. these results reaffirm what we are doing. It gives us confidence to continue treating low-risk patients and being comfortable with that.”

He added: “Outside the U.S., the guidelines are a little different. Maybe we should reconsider some of these guidelines based on these data.”

David Moliterno, MD, Gill Heart and Vascular Institute, Lexington, Ky., who is not involved in the TAVR studies, said: “The results provide a little more reassurance ... that will go a little way further.”

“Uncertainty remains regarding long-term durability of the transcatheter valve in low-risk patients who are generally younger and likely more active than higher-risk cohorts,” he added. “The current 3-year results provide more confidence as the outcome curves for death and disabling stroke are trending in the right direction for TAVR versus surgery.”

Dr. Moliterno pointed out that while rates of paravalvular regurgitation and permanent pacemaker placement are decreasing with newer generation Evolut devices and implantation techniques, he noted that according to the U.S. Social Security Administration, patients aged 74 years as enrolled in this low-risk cohort have an additional life expectancy of approximately 12 years. “So, we have more device durability (and coronary access feasibility) to prove.”

In his presentation, Dr. Forrest explained that TAVR is now approved in the United States for all patients with aortic stenosis regardless of surgical risk and has become the dominant form of aortic valve replacement. Current ACC/AHA guidelines recommend that heart teams utilize a shared decision-making process when discussing aortic valve replacement with patients aged 65-80 years. In younger, lower-risk patients, the faster recovery and short-term benefits after TAVR must be balanced with long-term durability; however, only limited intermediate and long-term data exist to guide such discussions in this patient population.

The Evolut Low Risk trial randomly assigned 1,414 patients in need of aortic valve replacement to TAVR with a self-expanding, supra-annular valve or surgery. Results at 1 and 2 years have shown a similar benefit in the primary endpoint of all-cause mortality/disabling stroke for the less invasive TAVR procedure.  

The current 3-year results suggest the benefit appears to be maintained out for another year. 

The main results show that the rate of death or disabling stroke was 7.4% in the TAVR group versus 10.4% in the surgery group, giving a hazard ratio of 0.70 (P = .051).

In the JACC paper, the authors report that the absolute difference between treatment arms for all-cause mortality or disabling stroke remained broadly consistent over time: –1.8% at year 1; –2.0% at year 2; and –2.9% at year 3.

Other key results on valve durability show that mild paravalvular regurgitation was increased in the TAVR group (20.3%) versus 2.5% with surgery. However, rates of moderate or greater paravalvular regurgitation for both groups were below 1% and not significantly different between groups.

Patients who underwent TAVR had significantly improved valve hemodynamics (mean gradient 9.1 mm Hg TAVR vs. 12.1 mm Hg surgery; P < .001) at 3 years.

However, pacemaker placement was much higher in the TAVR group (23.2%), compared with 9.1% in the surgery group.

On the other hand, the surgery group had a greater incidence of atrial fibrillation (40%) versus 13% with TAVR.

Quality-of-life results looked good in both groups.

“As we’ve come to expect, patients recover more quickly after TAVR, so at 30 days their quality of life is better than those who have undergone surgery,” Dr. Forrest commented. “But by 1 year, both groups are doing exceptionally well and, remarkably, here by 3 years both groups have greater than a 20-point increase in their KCCQ score, showing a very large improvement in quality of life.”

Discussant of these latest results at the ACC late-breaking trials session, James Hermiller, MD, St. Vincent Ascension Heart Center, Indianapolis, said: “This 3-year data continues to demonstrate that the gift of TAVR keeps giving.”

Noting that the divergence in the effect curves was primarily driven by mortality rather than stroke, he asked whether this was cardiac or noncardiac mortality that was reduced.

Dr. Forrest responded: “It was a fairly equal contribution – a little bit more cardiac death. We have to remember that although the average age in this study was 74, there were some patients over 80 who were still low-surgical-risk included so we are going to see noncardiac death as well.”

Dr. Hermiller drew attention to the high pacemaker rate in the TAVR group and asked how these patients fared in comparison to those who didn’t need a pacemaker.

Dr. Forrest replied: “I think it’s fair to say that putting in a pacemaker is not a benign procedure. Patients who got a pacemaker did slightly worse than those who didn’t get a pacemaker, so we need to try to drive that rate down.”

He added that the number of patients needing a pacemaker after TAVR has come down with new implantation techniques and new generation valves.

“We realize that using a cusp overlap technique can significantly reduce the need for a pacemaker, and we see from registry data that with the use of this new technique the need for a pacemaker has dropped down to 8%-9%, significantly less than seen in this study,” Dr. Forrest commented.    

Dr. Hermiller also asked about how TAVR affects future access for catheterization or percutaneous coronary intervention.  

Dr. Forrest noted that 24 patients in the TAVR group required PCI in first 3 years, and all the PCI procedures had been successful. He noted that operators reported the procedure to be easy or moderately easy in about 75%-80% of cases and difficult in about 20% of patients. “So, it is slightly more challenging to engage the coronaries and have to go through the frame, but it is very feasible.”

Dr. Forrest concluded that: “These results provide patients and heart teams important data to aid in the shared decision-making process.”

But he acknowledged that longer term data are still needed. “And the potential impact that hemodynamics, valve design, new pacemakers, and other secondary endpoints have on long-term outcomes will be important to follow in this group of low-risk patients.”

The Evolut Low Risk trial was funded by Medtronic. Dr. Forrest has received grant support/research contracts and consultant fees/honoraria/speakers bureau fees from Edwards Lifesciences and Medtronic.

A version of this article first appeared on Medscape.com.

The Diagnosis: Superficial Angiomyxoma

Superficial angiomyxoma is a rare, benign, cutaneous tumor of a myxoid matrix and blood vessels that was first described in association with Carney complex.¹ Tumors may be solitary or multiple. A recent review of cases in the literature revealed a roughly equal distribution of superficial angiomyxomas in males and females occurring most frequently on the head and neck, extremities, and trunk or back. The peak incidence is between the fourth and fifth decades of life.² Superficial angiomyxomas can occur sporadically or in association with Carney complex, an autosomal-dominant condition with germline inactivating mutations in protein kinase A, PRKAR1A. Interestingly, sporadic cases of superficial angiomyxoma also have shown loss of PRKAR1A expression on immunohistochemistry (IHC).³

Common histologic mimics of superficial angiomyxoma include aggressive angiomyxoma and angiomyofibroblastoma.⁴ It is thought that these 3 distinct tumor entities may arise from a common pluripotent cell of origin located near connective tissue vasculature, which may contribute to the similarities observed between them.⁵ For example, aggressive angiomyxomas and angiomyofibroblastomas also demonstrate a similar myxoid background and vascular proliferation that can closely mimic superficial angiomyxomas clinically. However, the vessels of superficial angiomyxomas tend to be long and thin walled, while aggressive angiomyxomas are characterized by large and thick-walled vessels and angiomyofibroblastomas by abundant smaller vessels. Additionally, unlike superficial angiomyxomas, both aggressive angiomyxomas and angiomyofibroblastomas typically occur in the genital tract of young to middle-aged women.⁶

Histopathologic examination is imperative for differentiating between superficial angiomyxoma and more aggressive histologic mimics. Superficial angiomyxomas typically consist of a rich myxoid stroma, thin-walled or arborizing blood vessels, and spindled to stellate fibroblastlike cells (quiz image 2).³ Although not prominent in our case, superficial angiomyxomas also frequently present with stromal neutrophils and epithelial components, including keratinous cysts, basaloid buds, and strands of squamous epithelium.⁷ Minimal cellular atypia, mitotic activity, and nuclear pleomorphism often are seen, with IHC negative for desmin, estrogen receptor, and progesterone receptor; positive for CD34 and smooth muscle actin; and variable for S-100 and muscle-specific actin. Although IHC has limited utility in the diagnosis of superficial angiomyxomas, it may be useful to rule out other differential diagnoses.^2,3 Superficial angiomyxomas usually show fibroblastic stromal cells, proteoglycan matrix, and collagen fibers on electron microscopy.⁸ Importantly, histopathologic examination of aggressive angiomyxoma will comparatively present with more invasive, infiltrative, and less well-circumscribed tumors.⁹ Other differential diagnoses on histology may include neurofibroma, focal cutaneous mucinosis, spindle cell lipoma, and myxofibrosarcoma. Additional considerations include fibroepithelial polyp, nevus lipomatosis, angiomyxolipoma, and anetoderma.

An important differential diagnosis in the evaluation of superficial angiomyxoma is neurofibroma, a benign peripheral nerve sheath tumor that presents as a smooth, flesh-colored, and painless papule or nodule commonly associated with the buttonhole sign. Histopathology of neurofibroma features elongated spindle cells with comma-shaped or buckled wavy nuclei and variably sized collagen bundles described as “shredded carrots” (Figure 1).¹⁰ Occasional mast cells also can be seen. Immunohistochemistry targeting elements of peripheral nerve sheaths may assist in the diagnosis of neurofibromas, including positive S-100 and SOX10 in Schwann cells, epithelial membrane antigen in perineural cells, and fingerprint positivity for CD34 in fibroblasts.¹⁰

Cutaneous mucinoses encompass a diverse group of connective tissue disorders characterized by accumulation of mucin in the skin. Solitary focal cutaneous mucinoses (FCMs) are individual isolated lesions of mucin deposits that are unassociated with systemic conditions.¹¹ Conversely, multiple FCMs presenting with multiple cutaneous lesions also have been described in association with systemic diseases such as scleroderma, systemic lupus erythematosus, and thyroid disease.¹² Solitary FCM typically presents as an asymptomatic, flesh-colored papule or nodule on the extremities. It often arises in mid to late adulthood with a slightly increased frequency among males.¹² Histopathology of solitary FCM commonly demonstrates a dome-shaped pool of basophilic mucin in the upper dermis sparing involvement of the underlying subcutaneous tissue (Figure 2).¹³ Notably, FCM often lacks the vascularity as well as stromal neutrophils and epithelial elements that are seen in superficial angiomyxomas. Although hematoxylin and eosin stains can be sufficient for diagnosis of solitary FCM, additional stains for mucin such as Alcian blue, colloidal iron, or toluidine blue also may be considered to support the diagnosis.¹²

Spindle cell lipomas (SCLs) are rare, benign, subcutaneous, adipocytic tumors that arise on the upper back, posterior neck, or shoulders of middle-aged or elderly adult males.¹⁴ The clinical presentation often is an asymptomatic, well-circumscribed, mobile subcutaneous mass that is firmer than a common lipoma. Histologically, SCLs are characterized by mature adipocytes, spindle cells, and wire or ropelike collagen fibers in a myxoid background (Figure 3). The spindle cells usually are bland with a notable bipolar shape and blunted ends. Infiltrative growth patterns or mitotic figures are uncommon. Diagnosis can be supported by IHC, as SCLs stain diffusely positive for CD34 with loss of the retinoblastoma protein.⁷

Another important differential diagnosis to consider is myxofibrosarcoma, a rare and malignant myxoid cutaneous tumor. Clinically, it presents asymptomatically as an indolent, slow-growing nodule on the limbs and limb girdles.⁷ Histopathologic features demonstrate a multilobular tumor composed of a mixture of hypocellular and hypercellular regions with incomplete fibrous septae (Figure 4). The presence of curvilinear vasculature is characteristic. Multinucleated giant cells and cellular atypia with nuclear pleomorphism also can be seen. Although IHC findings generally are not specific, they can be used to rule out other potential diagnoses. Myxofibrosarcomas stain positive for vimentin and occasionally smooth muscle actin, muscle-specific actin, and CD34.⁷

Superficial angiomyxomas are benign; however, excision is recommended to distinguish between mimics. Local recurrence after excision is common in 30% to 40% of patients.¹⁵ Mohs micrographic surgery has been considered, especially if the following are present: tumor characteristics (eg, poorly circumscribed), location (eg, head and neck or other cosmetically or functionally sensitive areas), and likelihood of recurrence (high for superficial angiomyxomas). 16 This case otherwise highlights a rare example of superficial angiomyxomas involving the buttocks.

The Diagnosis: Superficial Angiomyxoma

Superficial angiomyxoma is a rare, benign, cutaneous tumor of a myxoid matrix and blood vessels that was first described in association with Carney complex.¹ Tumors may be solitary or multiple. A recent review of cases in the literature revealed a roughly equal distribution of superficial angiomyxomas in males and females occurring most frequently on the head and neck, extremities, and trunk or back. The peak incidence is between the fourth and fifth decades of life.² Superficial angiomyxomas can occur sporadically or in association with Carney complex, an autosomal-dominant condition with germline inactivating mutations in protein kinase A, PRKAR1A. Interestingly, sporadic cases of superficial angiomyxoma also have shown loss of PRKAR1A expression on immunohistochemistry (IHC).³

Common histologic mimics of superficial angiomyxoma include aggressive angiomyxoma and angiomyofibroblastoma.⁴ It is thought that these 3 distinct tumor entities may arise from a common pluripotent cell of origin located near connective tissue vasculature, which may contribute to the similarities observed between them.⁵ For example, aggressive angiomyxomas and angiomyofibroblastomas also demonstrate a similar myxoid background and vascular proliferation that can closely mimic superficial angiomyxomas clinically. However, the vessels of superficial angiomyxomas tend to be long and thin walled, while aggressive angiomyxomas are characterized by large and thick-walled vessels and angiomyofibroblastomas by abundant smaller vessels. Additionally, unlike superficial angiomyxomas, both aggressive angiomyxomas and angiomyofibroblastomas typically occur in the genital tract of young to middle-aged women.⁶

Histopathologic examination is imperative for differentiating between superficial angiomyxoma and more aggressive histologic mimics. Superficial angiomyxomas typically consist of a rich myxoid stroma, thin-walled or arborizing blood vessels, and spindled to stellate fibroblastlike cells (quiz image 2).³ Although not prominent in our case, superficial angiomyxomas also frequently present with stromal neutrophils and epithelial components, including keratinous cysts, basaloid buds, and strands of squamous epithelium.⁷ Minimal cellular atypia, mitotic activity, and nuclear pleomorphism often are seen, with IHC negative for desmin, estrogen receptor, and progesterone receptor; positive for CD34 and smooth muscle actin; and variable for S-100 and muscle-specific actin. Although IHC has limited utility in the diagnosis of superficial angiomyxomas, it may be useful to rule out other differential diagnoses.^2,3 Superficial angiomyxomas usually show fibroblastic stromal cells, proteoglycan matrix, and collagen fibers on electron microscopy.⁸ Importantly, histopathologic examination of aggressive angiomyxoma will comparatively present with more invasive, infiltrative, and less well-circumscribed tumors.⁹ Other differential diagnoses on histology may include neurofibroma, focal cutaneous mucinosis, spindle cell lipoma, and myxofibrosarcoma. Additional considerations include fibroepithelial polyp, nevus lipomatosis, angiomyxolipoma, and anetoderma.

An important differential diagnosis in the evaluation of superficial angiomyxoma is neurofibroma, a benign peripheral nerve sheath tumor that presents as a smooth, flesh-colored, and painless papule or nodule commonly associated with the buttonhole sign. Histopathology of neurofibroma features elongated spindle cells with comma-shaped or buckled wavy nuclei and variably sized collagen bundles described as “shredded carrots” (Figure 1).¹⁰ Occasional mast cells also can be seen. Immunohistochemistry targeting elements of peripheral nerve sheaths may assist in the diagnosis of neurofibromas, including positive S-100 and SOX10 in Schwann cells, epithelial membrane antigen in perineural cells, and fingerprint positivity for CD34 in fibroblasts.¹⁰

Cutaneous mucinoses encompass a diverse group of connective tissue disorders characterized by accumulation of mucin in the skin. Solitary focal cutaneous mucinoses (FCMs) are individual isolated lesions of mucin deposits that are unassociated with systemic conditions.¹¹ Conversely, multiple FCMs presenting with multiple cutaneous lesions also have been described in association with systemic diseases such as scleroderma, systemic lupus erythematosus, and thyroid disease.¹² Solitary FCM typically presents as an asymptomatic, flesh-colored papule or nodule on the extremities. It often arises in mid to late adulthood with a slightly increased frequency among males.¹² Histopathology of solitary FCM commonly demonstrates a dome-shaped pool of basophilic mucin in the upper dermis sparing involvement of the underlying subcutaneous tissue (Figure 2).¹³ Notably, FCM often lacks the vascularity as well as stromal neutrophils and epithelial elements that are seen in superficial angiomyxomas. Although hematoxylin and eosin stains can be sufficient for diagnosis of solitary FCM, additional stains for mucin such as Alcian blue, colloidal iron, or toluidine blue also may be considered to support the diagnosis.¹²

Spindle cell lipomas (SCLs) are rare, benign, subcutaneous, adipocytic tumors that arise on the upper back, posterior neck, or shoulders of middle-aged or elderly adult males.¹⁴ The clinical presentation often is an asymptomatic, well-circumscribed, mobile subcutaneous mass that is firmer than a common lipoma. Histologically, SCLs are characterized by mature adipocytes, spindle cells, and wire or ropelike collagen fibers in a myxoid background (Figure 3). The spindle cells usually are bland with a notable bipolar shape and blunted ends. Infiltrative growth patterns or mitotic figures are uncommon. Diagnosis can be supported by IHC, as SCLs stain diffusely positive for CD34 with loss of the retinoblastoma protein.⁷

Another important differential diagnosis to consider is myxofibrosarcoma, a rare and malignant myxoid cutaneous tumor. Clinically, it presents asymptomatically as an indolent, slow-growing nodule on the limbs and limb girdles.⁷ Histopathologic features demonstrate a multilobular tumor composed of a mixture of hypocellular and hypercellular regions with incomplete fibrous septae (Figure 4). The presence of curvilinear vasculature is characteristic. Multinucleated giant cells and cellular atypia with nuclear pleomorphism also can be seen. Although IHC findings generally are not specific, they can be used to rule out other potential diagnoses. Myxofibrosarcomas stain positive for vimentin and occasionally smooth muscle actin, muscle-specific actin, and CD34.⁷

Superficial angiomyxomas are benign; however, excision is recommended to distinguish between mimics. Local recurrence after excision is common in 30% to 40% of patients.¹⁵ Mohs micrographic surgery has been considered, especially if the following are present: tumor characteristics (eg, poorly circumscribed), location (eg, head and neck or other cosmetically or functionally sensitive areas), and likelihood of recurrence (high for superficial angiomyxomas). 16 This case otherwise highlights a rare example of superficial angiomyxomas involving the buttocks.

The Diagnosis: Superficial Angiomyxoma

Superficial angiomyxoma is a rare, benign, cutaneous tumor of a myxoid matrix and blood vessels that was first described in association with Carney complex.¹ Tumors may be solitary or multiple. A recent review of cases in the literature revealed a roughly equal distribution of superficial angiomyxomas in males and females occurring most frequently on the head and neck, extremities, and trunk or back. The peak incidence is between the fourth and fifth decades of life.² Superficial angiomyxomas can occur sporadically or in association with Carney complex, an autosomal-dominant condition with germline inactivating mutations in protein kinase A, PRKAR1A. Interestingly, sporadic cases of superficial angiomyxoma also have shown loss of PRKAR1A expression on immunohistochemistry (IHC).³

Common histologic mimics of superficial angiomyxoma include aggressive angiomyxoma and angiomyofibroblastoma.⁴ It is thought that these 3 distinct tumor entities may arise from a common pluripotent cell of origin located near connective tissue vasculature, which may contribute to the similarities observed between them.⁵ For example, aggressive angiomyxomas and angiomyofibroblastomas also demonstrate a similar myxoid background and vascular proliferation that can closely mimic superficial angiomyxomas clinically. However, the vessels of superficial angiomyxomas tend to be long and thin walled, while aggressive angiomyxomas are characterized by large and thick-walled vessels and angiomyofibroblastomas by abundant smaller vessels. Additionally, unlike superficial angiomyxomas, both aggressive angiomyxomas and angiomyofibroblastomas typically occur in the genital tract of young to middle-aged women.⁶

Histopathologic examination is imperative for differentiating between superficial angiomyxoma and more aggressive histologic mimics. Superficial angiomyxomas typically consist of a rich myxoid stroma, thin-walled or arborizing blood vessels, and spindled to stellate fibroblastlike cells (quiz image 2).³ Although not prominent in our case, superficial angiomyxomas also frequently present with stromal neutrophils and epithelial components, including keratinous cysts, basaloid buds, and strands of squamous epithelium.⁷ Minimal cellular atypia, mitotic activity, and nuclear pleomorphism often are seen, with IHC negative for desmin, estrogen receptor, and progesterone receptor; positive for CD34 and smooth muscle actin; and variable for S-100 and muscle-specific actin. Although IHC has limited utility in the diagnosis of superficial angiomyxomas, it may be useful to rule out other differential diagnoses.^2,3 Superficial angiomyxomas usually show fibroblastic stromal cells, proteoglycan matrix, and collagen fibers on electron microscopy.⁸ Importantly, histopathologic examination of aggressive angiomyxoma will comparatively present with more invasive, infiltrative, and less well-circumscribed tumors.⁹ Other differential diagnoses on histology may include neurofibroma, focal cutaneous mucinosis, spindle cell lipoma, and myxofibrosarcoma. Additional considerations include fibroepithelial polyp, nevus lipomatosis, angiomyxolipoma, and anetoderma.

An important differential diagnosis in the evaluation of superficial angiomyxoma is neurofibroma, a benign peripheral nerve sheath tumor that presents as a smooth, flesh-colored, and painless papule or nodule commonly associated with the buttonhole sign. Histopathology of neurofibroma features elongated spindle cells with comma-shaped or buckled wavy nuclei and variably sized collagen bundles described as “shredded carrots” (Figure 1).¹⁰ Occasional mast cells also can be seen. Immunohistochemistry targeting elements of peripheral nerve sheaths may assist in the diagnosis of neurofibromas, including positive S-100 and SOX10 in Schwann cells, epithelial membrane antigen in perineural cells, and fingerprint positivity for CD34 in fibroblasts.¹⁰

Cutaneous mucinoses encompass a diverse group of connective tissue disorders characterized by accumulation of mucin in the skin. Solitary focal cutaneous mucinoses (FCMs) are individual isolated lesions of mucin deposits that are unassociated with systemic conditions.¹¹ Conversely, multiple FCMs presenting with multiple cutaneous lesions also have been described in association with systemic diseases such as scleroderma, systemic lupus erythematosus, and thyroid disease.¹² Solitary FCM typically presents as an asymptomatic, flesh-colored papule or nodule on the extremities. It often arises in mid to late adulthood with a slightly increased frequency among males.¹² Histopathology of solitary FCM commonly demonstrates a dome-shaped pool of basophilic mucin in the upper dermis sparing involvement of the underlying subcutaneous tissue (Figure 2).¹³ Notably, FCM often lacks the vascularity as well as stromal neutrophils and epithelial elements that are seen in superficial angiomyxomas. Although hematoxylin and eosin stains can be sufficient for diagnosis of solitary FCM, additional stains for mucin such as Alcian blue, colloidal iron, or toluidine blue also may be considered to support the diagnosis.¹²

Spindle cell lipomas (SCLs) are rare, benign, subcutaneous, adipocytic tumors that arise on the upper back, posterior neck, or shoulders of middle-aged or elderly adult males.¹⁴ The clinical presentation often is an asymptomatic, well-circumscribed, mobile subcutaneous mass that is firmer than a common lipoma. Histologically, SCLs are characterized by mature adipocytes, spindle cells, and wire or ropelike collagen fibers in a myxoid background (Figure 3). The spindle cells usually are bland with a notable bipolar shape and blunted ends. Infiltrative growth patterns or mitotic figures are uncommon. Diagnosis can be supported by IHC, as SCLs stain diffusely positive for CD34 with loss of the retinoblastoma protein.⁷

Another important differential diagnosis to consider is myxofibrosarcoma, a rare and malignant myxoid cutaneous tumor. Clinically, it presents asymptomatically as an indolent, slow-growing nodule on the limbs and limb girdles.⁷ Histopathologic features demonstrate a multilobular tumor composed of a mixture of hypocellular and hypercellular regions with incomplete fibrous septae (Figure 4). The presence of curvilinear vasculature is characteristic. Multinucleated giant cells and cellular atypia with nuclear pleomorphism also can be seen. Although IHC findings generally are not specific, they can be used to rule out other potential diagnoses. Myxofibrosarcomas stain positive for vimentin and occasionally smooth muscle actin, muscle-specific actin, and CD34.⁷

Superficial angiomyxomas are benign; however, excision is recommended to distinguish between mimics. Local recurrence after excision is common in 30% to 40% of patients.¹⁵ Mohs micrographic surgery has been considered, especially if the following are present: tumor characteristics (eg, poorly circumscribed), location (eg, head and neck or other cosmetically or functionally sensitive areas), and likelihood of recurrence (high for superficial angiomyxomas). 16 This case otherwise highlights a rare example of superficial angiomyxomas involving the buttocks.