Marilynn Larkin

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Cognitive function in children aged 18 months to 10 years is associated with the enrichment or depletion of specific species of gut microbes, new research reveals.

METHODOLOGY: 

• Researchers analyzed the relationship between the microbiome, neuroanatomy, and cognition (ie, the microbiome-gut-brain axis) in stool samples from 381 neurotypically developing children aged 40 days to 10 years (mean age, 2 years and 2 months).
• Stool samples were taken within a week of age-appropriate cognitive and behavioral assessments.
• Shotgun metagenomic sequencing was used to analyze the DNA of the organisms present in each sample.
• MRI data were obtained, with machine models then used to predict whether participants’ brain region volume was influenced by microbial profiles.

TAKEAWAY: 

• Researchers found increasing variation in microbial species and microbial gene functions in children older than 18 months, and the overall variation was significantly associated with variation in cognitive function scores.
• Several microbial species were significantly enriched in children with higher cognitive function scores (eg, Alistipes obesi, Asaccharobacter celatus, Eubacterium eligens, and Faecalibacterium prausnitzii), with Sutterella wadsworthensis being the only species significantly negatively associated with these scores.
• Machine models indicated that taxa key in predicting cognitive function were similarly important for predicting individual brain regions and subscales of cognitive function.

IN PRACTICE:

“Understanding the gut-brain-microbiome axis in early life is particularly important since differences or interventions in early life can have outsized and longer-term consequences than those at later ages,” the authors wrote.

SOURCE:

The study, led by Kevin S. Bonham, PhD, Wellesley College, Wellesley, Massachusetts, was published online on December 22, 2023, in Science Advances.

LIMITATIONS:

Use of multiple age-appropriate cognitive assessments enabled analysis across multiple developmental periods, but test-retest reliability and differences between test administrators may have introduced noise into these observations, particularly in the youngest children. The study period overlapped with the beginning of the pandemic, and score reductions due to the lockdowns were more pronounced in some age groups than during the recruitment period. 

DISCLOSURES:

The study was funded by the US National Institutes of Health and Wellcome: LEAP 1kD. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed. 

Is it living up to that promise? 

It seems that depends on where, how, and by whom it’s being implemented.
 

Clinical Trials vs the Real World

The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”

Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively). 

“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.

A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users). 

A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps. 

Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.

Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates. 

The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice. 
 

A ‘Mishmash’ of Methods

“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged. 

Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.

Other real-world studies look at detection by time, Dr. Sharma said. 

For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue. 

These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.

“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
 

Perceptions and Expectations

Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.

“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”

Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.

A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates. 

However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%). 

The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”

“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
 

Are Less Experienced Endoscopists Helped More?

It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this. 

A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.

Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.

But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.

“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.” 

Some studies reflect that dual benefit. 

The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.

An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).

A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”

Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively. 

The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
 

Improving the Algorithms 

Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications. 

Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.

“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.

AI can also play a role in health equity, she noted. 

“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said. 
 

Looking Ahead

Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.” 

Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation. 

In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.” 

Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Consuming nonsugar sweeteners (NSS) leads to significant changes in both stool and duodenal microbial diversity and composition and levels of circulating inflammatory markers.

METHODOLOGY:

• Researchers analyzed samples from the REIMAGINE (Revealing the Entire Intestinal Microbiota and its Associations with the Genetic, Immunologic, and Neuroendocrine Ecosystem) study to assess the potential effects of NSS consumption on the duodenal luminal microbiome.
• They analyzed subjects consuming non-aspartame nonsugar sweeteners (NANS; n = 35) and aspartame only (ASP; n = 9), who were compared with 55 control participants matched for age, sex, and body mass index.
• A subset of 40 participants provided stool samples for additional analysis.

TAKEAWAY:

• Duodenal alpha diversity was lower in NANS consumers vs controls.
• Duodenal relative abundance (RA) of Escherichia, Klebsiella, and Salmonella was lower in both NANS and ASP vs controls, whereas stool RA of these phylum Proteobacteria was increased in both NANS and ASP.
• Compared with controls, NANS and ASP differed in how they altered predicted duodenal microbial metabolic pathways, with NANS impacting polysaccharides biosynthesis and D-galactose degradation and ASP significantly enriching biosynthesis of cylindrospermopsin, a potential cancer-causing agent known to adversely impact the liver and nervous system.
• Circulating levels of interleukin (IL)-1b, a pro-inflammatory cytokine that plays a key role in the immune response, were significantly decreased in NANS vs controls, whereas IL-6 and IL-10, two cytokines with protective properties, were decreased in the ASP group vs controls.

IN PRACTICE:

“Given the crucial role played by small intestinal microbes in digestion, nutrient absorption, immune regulation, and endocrine functions, coupled with the substantial prevalence of NSS consumption among US adults (estimated at 41.4%), our findings have potential implications for metabolic and gastrointestinal health in a considerable proportion of the American adult population.”

SOURCE:

The study, conducted by Ava Hosseini, MPH, and colleagues at Cedars-Sinai, Los Angeles, was published online on November 22, 2023, in iScience.

LIMITATIONS:

The study population may not be representative of healthy individuals as they underwent upper endoscopy for various reasons (eg, evaluation of intestinal complaints). After exclusions, the duodenal sample size for the aspartame group was small. Samples were collected at a single timepoint, limiting the ability to establish causal relationships.

DISCLOSURES:

This research was supported by Frank Lee, the Monica Lester Charitable Trust, and the Elias, Genevieve, and Georgianna Atol Charitable Trust through their support of the Medically Associated Science and Technology Program, Cedars-Sinai, Los Angeles. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.

In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.

The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.

Comorbidities Count

The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).

Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).

Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).

Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.

Decade-Long Trend

ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).

Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.

Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
 

A version of this article appeared on Medscape.com.

Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.

In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.

The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.

Comorbidities Count

The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).

Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).

Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).

Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.

Decade-Long Trend

ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).

Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.

Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
 

A version of this article appeared on Medscape.com.

Emergency department (ED) visits by adults with diabetes increased by more than 25% since 2012, with the highest rates among Blacks and those aged over 65 years, a new data brief from the Centers for Disease Control and Prevention’s National Center for Health Statistics shows.

In 2021, diabetes was the eighth leading cause of death in the United States, according to the brief, published online on December 19, 2023. Its frequency is increasing in young people, and increasing age is a risk factor for hospitalization.

The latest data show that in 2020-2021, the overall annual ED visit rate was 72.2 visits per 1000 adults with diabetes, with no significant difference in terms of sex (75.1 visits per 1000 women vs 69.1 visits per 1000 men). By race/ethnicity, Blacks had the highest rates, at 135.5 visits per 1000 adults, followed by Whites (69.9) and Hispanics (52.3). The rates increased with age for both women and men, and among the three race/ethnic groups.

Comorbidities Count

The most ED visits were made by patients with diabetes and two to four other chronic conditions (541.4 visits per 1000 visits). Rates for patients without other chronic conditions were the lowest (90.2).

Among individuals with diabetes aged 18-44 years, ED visit rates were the highest for those with two to four other chronic conditions (402.0) and lowest among those with five or more other conditions (93.8).

Among patients aged 45-64 years, ED visit rates were the highest for those with two to four other chronic conditions (526.4) and lowest for those without other conditions (87.7). In the 65 years and older group, rates were the highest for individuals with two to four other chronic conditions (605.2), followed by five or more conditions (217.7), one other condition (140.6), and no other conditions (36.5).

Notably, the ED visit rates for those with two to four or five or more other chronic conditions increased with age, whereas visits for those with no other chronic conditions or one other condition decreased with age.

Decade-Long Trend

ED visit rates among adults with diabetes increased throughout the past decade, from 48.6 visits per 1000 adults in 2012 to 74.9 per 1000 adults in 2021. Rates for those aged 65 and older were higher than all other age groups, increasing from 113.4 to 156.8. Increases were also seen among those aged 45-64 years (53.1 in 2012 to 89.2 in 2021) and 18-44 (20.9 in 2012 to 26.4 in 2016, then plateauing from 2016-2021).

Data are based on a sample of 4051 ED visits, representing about 18,238,000 average annual visits made by adults with diabetes to nonfederal, general, and short-stay hospitals during 2020-2021.

Taken together, these most recent estimates “show an increasing trend in rates by adults with diabetes in the ED setting,” the authors concluded.
 

A version of this article appeared on Medscape.com.