It's hardly news that the United States is experiencing a mental health crisis -- the CDC says as much. But experts in the field say that the current administration has severely compounded the problem by eliminating agency funding and national programs, slashing research grants and data resources, and creating new barriers to behavioral health care.

Philanthropic foundations aim to do what they can to address the shortfall. The numbers, however, just don't add up.

"Some big foundations and philanthropies have said they're going to increase what they give out in the next 4 years, but they'll never be able to fill the gap," said Morgan F. McDonald, MD, national director of population health at the Milbank Memorial Fund in New York City, which works with states on health policy. "Even if every one of them were to spend down their endowments, they still couldn't."

Given the financial limitations, some foundations are taking a different tack. While looking for ways to join forces with fellow nonprofits, they are providing emergency grants to bridge funding in the short term to keep research from grinding to a halt.

Budget Cuts Reach Far and Wide

Mental health research certainly didn't escape the extensive grant cancellations at the National Institutes of Health and the National Science Foundation.

"It's already affecting our ability to stay on the cutting edge of research, best practices, and treatment approaches," said Zainab Okolo, EdD, senior vice president of policy, advocacy, and government relations at The Jed Foundation in New York City, which focuses on the emotional health of teens and young adults.

The upheaval is evident in an array of government agencies. The Health Resources and Services Administration, which last year awarded $12 billion in grants to community health centers and addiction treatment services, has seen > one-fourth of its staff eliminated. The Substance Abuse and Mental Health Services Administration has lost more than a third of its staff as federal cuts took a $1 billion bite out of its operating budget. The Education Department has halted $1 billion in grants used to hire mental health workers in school districts nationwide.

"We're very, very concerned about cuts to behavioral health systems," said Alonzo Plough, PhD, chief science officer at the Robert Wood Johnson Foundation in Princeton, New Jersey. "Doctors and nurses working in safety-net clinics are seeing tremendous reductions."

All in all, the new tax and spending law means $1 trillion in cuts to health care programs including Medicaid -- the nation's largest payer for mental health services -- Medicare, and Affordable Care Act insurance. An estimated 10 million Americans are expected to lose their health coverage as a result.

"When accessibility to care goes down, there's a chance that more people will die by suicide," said Jill Harkavy-Friedman, PhD, senior vice president of research at the American Foundation for Suicide Prevention. "But it also means people will come into care later in the course of their difficulties. Health professionals will be dealing with worse problems."

Foundations Take Emergency Measures

Even if private dollars can't replace what's been lost, philanthropic and medical foundations are stepping up.

We're seeing a lot of foundations and funders that are shifting their funding," said Alyson Niemann, CEO of Mindful Philanthropy, an organization that works with > 1000 private funders to marshal resources for mental health. This year, in response to federal cuts, "many increased funding to health and well-being, doubling or even tripling it," Niemann noted.

"They're making a great deal of effort to respond with emergency funds, really getting in the trenches and being good partners to their grantees," she said. "We've seen them asking deliberate questions, thinking about where their funding can have the most impact."

The American Psychological Foundation (APF), a longtime supporter of research and innovation, is addressing the current crisis with 2 initiatives, Michelle Quist Ryder, PhD, the organization's CEO, explained in an email. The first is APF Director Action, which funds innovative interventions at the community level. The second, Direct Action Crisis Funding Grants, will help continue research that is at risk of stalling because of budget cuts.

"Studies that are 'paused' or lose funding often cannot simply pick back up where they left off. Having to halt progress on a project can invalidate the work already completed," Ryder wrote. "These Direct Action Crisis Grants help bridge funding gaps and keep research viable."

At the same time, collaboration between foundations is becoming more widespread as they seek to maximize their impact. Philanthropic organizations are sharing ideas and best practices as well as pooling fundings.

"The goal of philanthropy is to help people," Harkavy-Friedman said. "There's strength in numbers and more dollars in numbers."

Some See Hope in Raised Voices

Despite the emergency scrambling, many of those in the trenches remain surprisingly optimistic. Some point out that the current turmoil has put a helpful spotlight on behavioral health care. Practitioners, meanwhile, have an essential role to play.

"There's a reason that things were the way they were: People advocated for many years to get where we've gotten," Harkavy-Friedman said, citing veterans' mental health care, the national violent death reporting system, and 988 as examples. "We have to raise our voices louder -- professionals in particular, because they know the impact a person in the general public many not fully grasp."

As a growing numbers of health professionals call attention to the damage wrought by deep cuts in the federal budget, foundation executives see an opportunity.

"In the mental health field, there's a deficit in the narrative, where there's a lot of focus on crisis. What we're hoping to do is shift the narrative toward 'How do we flourish together?'" Niemann said. "Sometimes deficits are where the most incredible innovations appear."

Debbie Koenig is a health writer whose work has been published by WebMD, The New York Times, and The Washington Post.

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

It's hardly news that the United States is experiencing a mental health crisis -- the CDC says as much. But experts in the field say that the current administration has severely compounded the problem by eliminating agency funding and national programs, slashing research grants and data resources, and creating new barriers to behavioral health care.

Philanthropic foundations aim to do what they can to address the shortfall. The numbers, however, just don't add up.

"Some big foundations and philanthropies have said they're going to increase what they give out in the next 4 years, but they'll never be able to fill the gap," said Morgan F. McDonald, MD, national director of population health at the Milbank Memorial Fund in New York City, which works with states on health policy. "Even if every one of them were to spend down their endowments, they still couldn't."

Given the financial limitations, some foundations are taking a different tack. While looking for ways to join forces with fellow nonprofits, they are providing emergency grants to bridge funding in the short term to keep research from grinding to a halt.

Budget Cuts Reach Far and Wide

Mental health research certainly didn't escape the extensive grant cancellations at the National Institutes of Health and the National Science Foundation.

"It's already affecting our ability to stay on the cutting edge of research, best practices, and treatment approaches," said Zainab Okolo, EdD, senior vice president of policy, advocacy, and government relations at The Jed Foundation in New York City, which focuses on the emotional health of teens and young adults.

The upheaval is evident in an array of government agencies. The Health Resources and Services Administration, which last year awarded $12 billion in grants to community health centers and addiction treatment services, has seen > one-fourth of its staff eliminated. The Substance Abuse and Mental Health Services Administration has lost more than a third of its staff as federal cuts took a $1 billion bite out of its operating budget. The Education Department has halted $1 billion in grants used to hire mental health workers in school districts nationwide.

"We're very, very concerned about cuts to behavioral health systems," said Alonzo Plough, PhD, chief science officer at the Robert Wood Johnson Foundation in Princeton, New Jersey. "Doctors and nurses working in safety-net clinics are seeing tremendous reductions."

All in all, the new tax and spending law means $1 trillion in cuts to health care programs including Medicaid -- the nation's largest payer for mental health services -- Medicare, and Affordable Care Act insurance. An estimated 10 million Americans are expected to lose their health coverage as a result.

"When accessibility to care goes down, there's a chance that more people will die by suicide," said Jill Harkavy-Friedman, PhD, senior vice president of research at the American Foundation for Suicide Prevention. "But it also means people will come into care later in the course of their difficulties. Health professionals will be dealing with worse problems."

Foundations Take Emergency Measures

Even if private dollars can't replace what's been lost, philanthropic and medical foundations are stepping up.

We're seeing a lot of foundations and funders that are shifting their funding," said Alyson Niemann, CEO of Mindful Philanthropy, an organization that works with > 1000 private funders to marshal resources for mental health. This year, in response to federal cuts, "many increased funding to health and well-being, doubling or even tripling it," Niemann noted.

"They're making a great deal of effort to respond with emergency funds, really getting in the trenches and being good partners to their grantees," she said. "We've seen them asking deliberate questions, thinking about where their funding can have the most impact."

The American Psychological Foundation (APF), a longtime supporter of research and innovation, is addressing the current crisis with 2 initiatives, Michelle Quist Ryder, PhD, the organization's CEO, explained in an email. The first is APF Director Action, which funds innovative interventions at the community level. The second, Direct Action Crisis Funding Grants, will help continue research that is at risk of stalling because of budget cuts.

"Studies that are 'paused' or lose funding often cannot simply pick back up where they left off. Having to halt progress on a project can invalidate the work already completed," Ryder wrote. "These Direct Action Crisis Grants help bridge funding gaps and keep research viable."

At the same time, collaboration between foundations is becoming more widespread as they seek to maximize their impact. Philanthropic organizations are sharing ideas and best practices as well as pooling fundings.

"The goal of philanthropy is to help people," Harkavy-Friedman said. "There's strength in numbers and more dollars in numbers."

Some See Hope in Raised Voices

Despite the emergency scrambling, many of those in the trenches remain surprisingly optimistic. Some point out that the current turmoil has put a helpful spotlight on behavioral health care. Practitioners, meanwhile, have an essential role to play.

"There's a reason that things were the way they were: People advocated for many years to get where we've gotten," Harkavy-Friedman said, citing veterans' mental health care, the national violent death reporting system, and 988 as examples. "We have to raise our voices louder -- professionals in particular, because they know the impact a person in the general public many not fully grasp."

As a growing numbers of health professionals call attention to the damage wrought by deep cuts in the federal budget, foundation executives see an opportunity.

"In the mental health field, there's a deficit in the narrative, where there's a lot of focus on crisis. What we're hoping to do is shift the narrative toward 'How do we flourish together?'" Niemann said. "Sometimes deficits are where the most incredible innovations appear."

Debbie Koenig is a health writer whose work has been published by WebMD, The New York Times, and The Washington Post.

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

It's hardly news that the United States is experiencing a mental health crisis -- the CDC says as much. But experts in the field say that the current administration has severely compounded the problem by eliminating agency funding and national programs, slashing research grants and data resources, and creating new barriers to behavioral health care.

Philanthropic foundations aim to do what they can to address the shortfall. The numbers, however, just don't add up.

"Some big foundations and philanthropies have said they're going to increase what they give out in the next 4 years, but they'll never be able to fill the gap," said Morgan F. McDonald, MD, national director of population health at the Milbank Memorial Fund in New York City, which works with states on health policy. "Even if every one of them were to spend down their endowments, they still couldn't."

Given the financial limitations, some foundations are taking a different tack. While looking for ways to join forces with fellow nonprofits, they are providing emergency grants to bridge funding in the short term to keep research from grinding to a halt.

Budget Cuts Reach Far and Wide

Mental health research certainly didn't escape the extensive grant cancellations at the National Institutes of Health and the National Science Foundation.

"It's already affecting our ability to stay on the cutting edge of research, best practices, and treatment approaches," said Zainab Okolo, EdD, senior vice president of policy, advocacy, and government relations at The Jed Foundation in New York City, which focuses on the emotional health of teens and young adults.

The upheaval is evident in an array of government agencies. The Health Resources and Services Administration, which last year awarded $12 billion in grants to community health centers and addiction treatment services, has seen > one-fourth of its staff eliminated. The Substance Abuse and Mental Health Services Administration has lost more than a third of its staff as federal cuts took a $1 billion bite out of its operating budget. The Education Department has halted $1 billion in grants used to hire mental health workers in school districts nationwide.

"We're very, very concerned about cuts to behavioral health systems," said Alonzo Plough, PhD, chief science officer at the Robert Wood Johnson Foundation in Princeton, New Jersey. "Doctors and nurses working in safety-net clinics are seeing tremendous reductions."

All in all, the new tax and spending law means $1 trillion in cuts to health care programs including Medicaid -- the nation's largest payer for mental health services -- Medicare, and Affordable Care Act insurance. An estimated 10 million Americans are expected to lose their health coverage as a result.

"When accessibility to care goes down, there's a chance that more people will die by suicide," said Jill Harkavy-Friedman, PhD, senior vice president of research at the American Foundation for Suicide Prevention. "But it also means people will come into care later in the course of their difficulties. Health professionals will be dealing with worse problems."

Foundations Take Emergency Measures

Even if private dollars can't replace what's been lost, philanthropic and medical foundations are stepping up.

We're seeing a lot of foundations and funders that are shifting their funding," said Alyson Niemann, CEO of Mindful Philanthropy, an organization that works with > 1000 private funders to marshal resources for mental health. This year, in response to federal cuts, "many increased funding to health and well-being, doubling or even tripling it," Niemann noted.

"They're making a great deal of effort to respond with emergency funds, really getting in the trenches and being good partners to their grantees," she said. "We've seen them asking deliberate questions, thinking about where their funding can have the most impact."

The American Psychological Foundation (APF), a longtime supporter of research and innovation, is addressing the current crisis with 2 initiatives, Michelle Quist Ryder, PhD, the organization's CEO, explained in an email. The first is APF Director Action, which funds innovative interventions at the community level. The second, Direct Action Crisis Funding Grants, will help continue research that is at risk of stalling because of budget cuts.

"Studies that are 'paused' or lose funding often cannot simply pick back up where they left off. Having to halt progress on a project can invalidate the work already completed," Ryder wrote. "These Direct Action Crisis Grants help bridge funding gaps and keep research viable."

At the same time, collaboration between foundations is becoming more widespread as they seek to maximize their impact. Philanthropic organizations are sharing ideas and best practices as well as pooling fundings.

"The goal of philanthropy is to help people," Harkavy-Friedman said. "There's strength in numbers and more dollars in numbers."

Some See Hope in Raised Voices

Despite the emergency scrambling, many of those in the trenches remain surprisingly optimistic. Some point out that the current turmoil has put a helpful spotlight on behavioral health care. Practitioners, meanwhile, have an essential role to play.

"There's a reason that things were the way they were: People advocated for many years to get where we've gotten," Harkavy-Friedman said, citing veterans' mental health care, the national violent death reporting system, and 988 as examples. "We have to raise our voices louder -- professionals in particular, because they know the impact a person in the general public many not fully grasp."

As a growing numbers of health professionals call attention to the damage wrought by deep cuts in the federal budget, foundation executives see an opportunity.

"In the mental health field, there's a deficit in the narrative, where there's a lot of focus on crisis. What we're hoping to do is shift the narrative toward 'How do we flourish together?'" Niemann said. "Sometimes deficits are where the most incredible innovations appear."

Debbie Koenig is a health writer whose work has been published by WebMD, The New York Times, and The Washington Post.

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

For Kelly, a retired Navy operations specialist, coping with depression and anxiety hindered her ability to enjoy everyday life. Then she elected to enter therapy, a decision she calls “transformative.”

“When I started doing therapy, it was like releasing the toxins, releasing the buildup of the fear or the rage or the overwhelming feelings of shame,” she says. “We can’t just hold on to it. Just telling the truth, it helps me every single day. It is so worth it.”

Kurt, an Army veteran, tried to power through his anxiety, depression, and survivor guilt. He didn’t have much faith in mental health therapy, thinking no one could relate to him. He was surprised, though, once he started treatment, how much his life improved. He now encourages other veterans to face their own mental health challenges, be it through virtual/mental health apps or in-person care.

“From getting help, every day of my life is better,” he says, “and I couldn’t be more grateful for it.”

Stories from Kelly and Kurt are 2 of 7 the US Department of Veterans Affairs (VA) highlighted during National Recovery Month, outlining how their lives were forever changed with the support of mental health care.

But for every Kelly and Kurt, there are thousands of individuals reluctant to seek mental health care. A analysis of 2019-2020 data from the National Health and Resilience in Veterans Study found that 924 (26%) of 4069 veterans met criteria for ≥ 1 psychological disorders, but only 12% reported engagement in mental health care. The researchers considered the role of protective psychosocial characteristics, such as grit (ie, “trait perseverance that extends to one’s decision or commitment to address mental health needs on one’s own; dispositional optimism; and purpose in life”). Veterans who reported mental dysfunction but scored highly on grit were less likely to be engaged in treatment. This pattern suggests higher levels of grit may reduce the likelihood of seeking treatment, “even in the presence of clinically meaningful distress.”

A 2004 study found only 23% to 40% of service members who screened positive for a mental disorder sought care. They often believed they would be seen as weak, or their unit leadership might treat them differently, and unit members would have less confidence in them. 

Given that military members and veterans are at increased risk of posttraumatic stress disorder (PTSD) in addition to mood, anxiety, and substance use disorders, any alternatives that increase their access to support and services are crucial. For those who aren’t disposed to office visits and group therapy, the answer may lie in mobile apps. 

In a recent randomized controlled trial, 201 veterans who screened positive for PTSD and alcohol use disorder were divided into 2 groups: a mobile mindfulness-based intervention group enhanced with brief alcohol intervention content (Mind Guide), and an active stress management program group. Mind Guide engagement was excellent, according to the study, with averages of > 31 logins and 5 hours of app use. At 16 weeks, the Mind Guide group showed significant reductions in PTSD symptoms (no differences emerged for alcohol use frequency). Mind Guide may be a valuable adjunct to more intensive in-person PTSD treatment by facilitating interest in services, integration into care, and/or sustainment of posttreatment improvements. The VA currently offers 16 apps, including MHA for Veterans, an app designed for patients to complete mental health assessments after their clinician assigned them. Other apps address a variety of issues, such as anger management, insomnia, chronic pain, and PTSD. 

Two apps were created with an eye toward specific communities. One, Veterans Wellness Path, was designed for American Indians and Alaska Natives with input from those veterans, their family members, and health care practitioners. It supports the transition from military service to home and encourages balance and connection with self, family, community, and environment. Similarly, WellWithin Coach was designed by the VA National Center for PTSD with input from women veterans and subject matter experts in women’s mental health.

Whatever form it takes—in-person or virtual—finding support that works can make all the difference for veterans. Kelly founded and serves as the executive director of Acta Non Verba: Youth Urban Farm Project, an organization that brings together > 3000 low-income youth and families annually to learn about urban farming, aiming to fill a gap in an area known as a food desert: “We do have the power and the right to wake up the next day and try to do something different,” she said.

For Kelly, a retired Navy operations specialist, coping with depression and anxiety hindered her ability to enjoy everyday life. Then she elected to enter therapy, a decision she calls “transformative.”

“When I started doing therapy, it was like releasing the toxins, releasing the buildup of the fear or the rage or the overwhelming feelings of shame,” she says. “We can’t just hold on to it. Just telling the truth, it helps me every single day. It is so worth it.”

Kurt, an Army veteran, tried to power through his anxiety, depression, and survivor guilt. He didn’t have much faith in mental health therapy, thinking no one could relate to him. He was surprised, though, once he started treatment, how much his life improved. He now encourages other veterans to face their own mental health challenges, be it through virtual/mental health apps or in-person care.

“From getting help, every day of my life is better,” he says, “and I couldn’t be more grateful for it.”

Stories from Kelly and Kurt are 2 of 7 the US Department of Veterans Affairs (VA) highlighted during National Recovery Month, outlining how their lives were forever changed with the support of mental health care.

But for every Kelly and Kurt, there are thousands of individuals reluctant to seek mental health care. A analysis of 2019-2020 data from the National Health and Resilience in Veterans Study found that 924 (26%) of 4069 veterans met criteria for ≥ 1 psychological disorders, but only 12% reported engagement in mental health care. The researchers considered the role of protective psychosocial characteristics, such as grit (ie, “trait perseverance that extends to one’s decision or commitment to address mental health needs on one’s own; dispositional optimism; and purpose in life”). Veterans who reported mental dysfunction but scored highly on grit were less likely to be engaged in treatment. This pattern suggests higher levels of grit may reduce the likelihood of seeking treatment, “even in the presence of clinically meaningful distress.”

A 2004 study found only 23% to 40% of service members who screened positive for a mental disorder sought care. They often believed they would be seen as weak, or their unit leadership might treat them differently, and unit members would have less confidence in them. 

Given that military members and veterans are at increased risk of posttraumatic stress disorder (PTSD) in addition to mood, anxiety, and substance use disorders, any alternatives that increase their access to support and services are crucial. For those who aren’t disposed to office visits and group therapy, the answer may lie in mobile apps. 

In a recent randomized controlled trial, 201 veterans who screened positive for PTSD and alcohol use disorder were divided into 2 groups: a mobile mindfulness-based intervention group enhanced with brief alcohol intervention content (Mind Guide), and an active stress management program group. Mind Guide engagement was excellent, according to the study, with averages of > 31 logins and 5 hours of app use. At 16 weeks, the Mind Guide group showed significant reductions in PTSD symptoms (no differences emerged for alcohol use frequency). Mind Guide may be a valuable adjunct to more intensive in-person PTSD treatment by facilitating interest in services, integration into care, and/or sustainment of posttreatment improvements. The VA currently offers 16 apps, including MHA for Veterans, an app designed for patients to complete mental health assessments after their clinician assigned them. Other apps address a variety of issues, such as anger management, insomnia, chronic pain, and PTSD. 

Two apps were created with an eye toward specific communities. One, Veterans Wellness Path, was designed for American Indians and Alaska Natives with input from those veterans, their family members, and health care practitioners. It supports the transition from military service to home and encourages balance and connection with self, family, community, and environment. Similarly, WellWithin Coach was designed by the VA National Center for PTSD with input from women veterans and subject matter experts in women’s mental health.

Whatever form it takes—in-person or virtual—finding support that works can make all the difference for veterans. Kelly founded and serves as the executive director of Acta Non Verba: Youth Urban Farm Project, an organization that brings together > 3000 low-income youth and families annually to learn about urban farming, aiming to fill a gap in an area known as a food desert: “We do have the power and the right to wake up the next day and try to do something different,” she said.

For Kelly, a retired Navy operations specialist, coping with depression and anxiety hindered her ability to enjoy everyday life. Then she elected to enter therapy, a decision she calls “transformative.”

“When I started doing therapy, it was like releasing the toxins, releasing the buildup of the fear or the rage or the overwhelming feelings of shame,” she says. “We can’t just hold on to it. Just telling the truth, it helps me every single day. It is so worth it.”

Kurt, an Army veteran, tried to power through his anxiety, depression, and survivor guilt. He didn’t have much faith in mental health therapy, thinking no one could relate to him. He was surprised, though, once he started treatment, how much his life improved. He now encourages other veterans to face their own mental health challenges, be it through virtual/mental health apps or in-person care.

“From getting help, every day of my life is better,” he says, “and I couldn’t be more grateful for it.”

Stories from Kelly and Kurt are 2 of 7 the US Department of Veterans Affairs (VA) highlighted during National Recovery Month, outlining how their lives were forever changed with the support of mental health care.

But for every Kelly and Kurt, there are thousands of individuals reluctant to seek mental health care. A analysis of 2019-2020 data from the National Health and Resilience in Veterans Study found that 924 (26%) of 4069 veterans met criteria for ≥ 1 psychological disorders, but only 12% reported engagement in mental health care. The researchers considered the role of protective psychosocial characteristics, such as grit (ie, “trait perseverance that extends to one’s decision or commitment to address mental health needs on one’s own; dispositional optimism; and purpose in life”). Veterans who reported mental dysfunction but scored highly on grit were less likely to be engaged in treatment. This pattern suggests higher levels of grit may reduce the likelihood of seeking treatment, “even in the presence of clinically meaningful distress.”

A 2004 study found only 23% to 40% of service members who screened positive for a mental disorder sought care. They often believed they would be seen as weak, or their unit leadership might treat them differently, and unit members would have less confidence in them. 

Given that military members and veterans are at increased risk of posttraumatic stress disorder (PTSD) in addition to mood, anxiety, and substance use disorders, any alternatives that increase their access to support and services are crucial. For those who aren’t disposed to office visits and group therapy, the answer may lie in mobile apps. 

In a recent randomized controlled trial, 201 veterans who screened positive for PTSD and alcohol use disorder were divided into 2 groups: a mobile mindfulness-based intervention group enhanced with brief alcohol intervention content (Mind Guide), and an active stress management program group. Mind Guide engagement was excellent, according to the study, with averages of > 31 logins and 5 hours of app use. At 16 weeks, the Mind Guide group showed significant reductions in PTSD symptoms (no differences emerged for alcohol use frequency). Mind Guide may be a valuable adjunct to more intensive in-person PTSD treatment by facilitating interest in services, integration into care, and/or sustainment of posttreatment improvements. The VA currently offers 16 apps, including MHA for Veterans, an app designed for patients to complete mental health assessments after their clinician assigned them. Other apps address a variety of issues, such as anger management, insomnia, chronic pain, and PTSD. 

Two apps were created with an eye toward specific communities. One, Veterans Wellness Path, was designed for American Indians and Alaska Natives with input from those veterans, their family members, and health care practitioners. It supports the transition from military service to home and encourages balance and connection with self, family, community, and environment. Similarly, WellWithin Coach was designed by the VA National Center for PTSD with input from women veterans and subject matter experts in women’s mental health.

Whatever form it takes—in-person or virtual—finding support that works can make all the difference for veterans. Kelly founded and serves as the executive director of Acta Non Verba: Youth Urban Farm Project, an organization that brings together > 3000 low-income youth and families annually to learn about urban farming, aiming to fill a gap in an area known as a food desert: “We do have the power and the right to wake up the next day and try to do something different,” she said.

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no disclosures.

 

A version of this article appeared on Medscape.com.

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no disclosures.

 

A version of this article appeared on Medscape.com.

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no disclosures.

 

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.

Veterans at risk of suicide may not share their suicidal ideation with their psychotherapists or may choose not to disclose enough detail to illustrate the depths of those thoughts due to feelings of shame or embarrassment, according to a newly published study. These individuals may view suicidal thoughts as a sign of weakness, fear involuntary hospitalization or prescriptions, or belong to marginalized groups who do not feel comfortable (or safe) to reveal their thoughts or intentions. This can make it difficult for mental health professionals to identify the exact details of a patient’s mindset and provide appropriate care. 

A veteran’s first—and sometimes only—stop may be their primary care practitioner (PCPs) rather than a mental health professional. A review of 40 studies found that although 45% of individuals who died by suicide had contact with PCPs within 1 month of their death, only 19% had contact with mental health services. Studies have also found that veterans disclose suicidal ideation during primary care visits closest to the actual suicide less than half the time.

Patients may have an appointment for medical, but not psychological reasons. In a study conducted at Portland Veterans Affairs Medical Center (VAMC), researchers reviewed the medical records of 112 veterans who died by suicide and had contact with a VAMC within 1 year prior to death. Of those last contacts, 32% were patient-initiated for new or exacerbated medical concerns, and 68% were follow-ups. 

In that study, health care professionals (HCPs) noted that 41 patients (37%) were experiencing emotional distress at the last contact, but 13 of 18 patients (72%) who were assessed for suicidal ideation at their last contact denied such thoughts. The study says this finding “highlights the complexity of addressing suicidal ideation and associated risk factors in health care settings.” Additionally, a number of veterans who died by suicide either did not have suicidal thoughts  at the time of their last contact with HCPs or denied such thoughts even when questioned. 

In 2018, the Veterans Health Administration (VHA) implemented the Suicide Risk Identification Strategy (Risk ID), an evidence-informed assessment that includes initial screening and subsequent evaluation. Veterans receiving VHA care are screened annually for suicidal ideation and behaviors. Most screening takes place in primary care and mental health specialty settings, but timely screening may not be enough to assess who is at risk if the patients aren’t being forthcoming about their thoughts and plans.

A recent cross-sectional national survey examined the frequency of self-reported “inaccurate disclosure” of suicidal ideation during initial screening and subsequent evaluation among 734 VHA patients screened in primary care.

Using the Risk ID process with the Columbia Suicide Severity Rating Scale Screener (C-SSRS), the study asked respondents about their previous suicide screening in 2021. Of the 734 respondents, 306 screened positive and 428 screened negative. One survey item asked about the extent to which veterans had accurately responded to the HCP when asked about suicidal thoughts, while another asked how likely they would discuss when they felt suicidal with their PCP.

The study found that inaccurate disclosure is not uncommon: When asked about suicidal thoughts, about one-fifth of screen-negative participants and two-fifths of screen-positive participants said they responded, “less than very accurately.”

In the screen-positive group, women and those who reported more barriers to care were less likely to discuss feeling suicidal. Veterans who had lower ratings of satisfaction with the screening process, patient-staff communication, and the therapeutic relationship reported being less likely to discuss times they were suicidal. Notably, among C-SSRS-negative patients, Black, American Indian/Alaska Native, Hispanic, Asian, and multiracial veterans were more likely than White veterans to inaccurately report suicidal thoughts. 

This is consistent with studies on medical mistrust and other research suggesting that veterans who have experienced identity-based discrimination may be less inclined to discuss suicidal thoughts with VHA HCPs. A large 2023 study surveyed veterans about why they might hold back such information. One Gulf War-era veteran, a Black woman, had encountered discrimination when filing her VA benefits claim, leading her to feel like the care system was not interested in helping her.

“It’s one of the main reasons why when I do go in, they don’t get an honest response,” she wrote in her survey response. “I feel that you’re not for me, you’re not trying to help me, you don’t wanna help me, and why even go through it, go through the motions it seems. So, I can come in feeling suicidal and I leave out feeling suicidal then.” 

Veterans typically welcome screening for suicidal risk. In a 2023 study, > 90% of veterans reported that it is appropriate to be asked about thoughts of suicide during primary care visits, and about one-half agreed that veterans should be asked about suicidal thoughts at every visit. 

For many, though, the level of trust they have with HCPs makes or breaks whether they discuss their suicidal ideation. Higher ratings of the therapeutic relationship with clinicians are associated with more frequent disclosure. However, the screen-positive group demonstrated higher rates of inaccurate disclosure than the screen-negative group. While this may seem counterintuitive, it is possible that screen-positive individuals did not fully disclose their thoughts on the initial screen, or did not fully disclose the severity of their thoughts during follow-up evaluations. Individuals who disclose suicidal thoughts during initial screening may be ambivalent about disclosure and/or become more concerned about consequences of disclosure as additional evaluation ensues. 

A 2013 study of 34 Operation Enduring Freedom/Operation Iraqi Freedom veterans found that veterans felt trying to suppress and avoid thoughts of suicide was “burdensome and exhausting.” Despite this, they often failed to disclose severe and pervasive suicidal thoughts when screened. Among the reasons was that they perceived the templated computer reminder process as “perfunctory and disrespectful.”

Research has found that HCPs who focuses on building relationships, demonstrates genuineness and empathy, and uses straightforward and understandable language promotes the trust that can result in more honest disclosure of suicidal thoughts. In the “inaccurate disclosure” study, some veterans reported they did not understand the screening questions, or the questions did not make sense to them. This aligns with prior research, which demonstrates that how HCPs and researchers conceptualize suicidal thoughts may not fit with patients’ experiences. A lack of shared terminology, they note, “may confound how we think about ‘under-disclosure,’ such that perhaps patients may not be trying to hide their thoughts so much as not finding screening questions applicable to their unique situations or experiences.”

Veterans at risk of suicide may not share their suicidal ideation with their psychotherapists or may choose not to disclose enough detail to illustrate the depths of those thoughts due to feelings of shame or embarrassment, according to a newly published study. These individuals may view suicidal thoughts as a sign of weakness, fear involuntary hospitalization or prescriptions, or belong to marginalized groups who do not feel comfortable (or safe) to reveal their thoughts or intentions. This can make it difficult for mental health professionals to identify the exact details of a patient’s mindset and provide appropriate care. 

A veteran’s first—and sometimes only—stop may be their primary care practitioner (PCPs) rather than a mental health professional. A review of 40 studies found that although 45% of individuals who died by suicide had contact with PCPs within 1 month of their death, only 19% had contact with mental health services. Studies have also found that veterans disclose suicidal ideation during primary care visits closest to the actual suicide less than half the time.

Patients may have an appointment for medical, but not psychological reasons. In a study conducted at Portland Veterans Affairs Medical Center (VAMC), researchers reviewed the medical records of 112 veterans who died by suicide and had contact with a VAMC within 1 year prior to death. Of those last contacts, 32% were patient-initiated for new or exacerbated medical concerns, and 68% were follow-ups. 

In that study, health care professionals (HCPs) noted that 41 patients (37%) were experiencing emotional distress at the last contact, but 13 of 18 patients (72%) who were assessed for suicidal ideation at their last contact denied such thoughts. The study says this finding “highlights the complexity of addressing suicidal ideation and associated risk factors in health care settings.” Additionally, a number of veterans who died by suicide either did not have suicidal thoughts  at the time of their last contact with HCPs or denied such thoughts even when questioned. 

In 2018, the Veterans Health Administration (VHA) implemented the Suicide Risk Identification Strategy (Risk ID), an evidence-informed assessment that includes initial screening and subsequent evaluation. Veterans receiving VHA care are screened annually for suicidal ideation and behaviors. Most screening takes place in primary care and mental health specialty settings, but timely screening may not be enough to assess who is at risk if the patients aren’t being forthcoming about their thoughts and plans.

A recent cross-sectional national survey examined the frequency of self-reported “inaccurate disclosure” of suicidal ideation during initial screening and subsequent evaluation among 734 VHA patients screened in primary care.

Using the Risk ID process with the Columbia Suicide Severity Rating Scale Screener (C-SSRS), the study asked respondents about their previous suicide screening in 2021. Of the 734 respondents, 306 screened positive and 428 screened negative. One survey item asked about the extent to which veterans had accurately responded to the HCP when asked about suicidal thoughts, while another asked how likely they would discuss when they felt suicidal with their PCP.

The study found that inaccurate disclosure is not uncommon: When asked about suicidal thoughts, about one-fifth of screen-negative participants and two-fifths of screen-positive participants said they responded, “less than very accurately.”

In the screen-positive group, women and those who reported more barriers to care were less likely to discuss feeling suicidal. Veterans who had lower ratings of satisfaction with the screening process, patient-staff communication, and the therapeutic relationship reported being less likely to discuss times they were suicidal. Notably, among C-SSRS-negative patients, Black, American Indian/Alaska Native, Hispanic, Asian, and multiracial veterans were more likely than White veterans to inaccurately report suicidal thoughts. 

This is consistent with studies on medical mistrust and other research suggesting that veterans who have experienced identity-based discrimination may be less inclined to discuss suicidal thoughts with VHA HCPs. A large 2023 study surveyed veterans about why they might hold back such information. One Gulf War-era veteran, a Black woman, had encountered discrimination when filing her VA benefits claim, leading her to feel like the care system was not interested in helping her.

“It’s one of the main reasons why when I do go in, they don’t get an honest response,” she wrote in her survey response. “I feel that you’re not for me, you’re not trying to help me, you don’t wanna help me, and why even go through it, go through the motions it seems. So, I can come in feeling suicidal and I leave out feeling suicidal then.” 

Veterans typically welcome screening for suicidal risk. In a 2023 study, > 90% of veterans reported that it is appropriate to be asked about thoughts of suicide during primary care visits, and about one-half agreed that veterans should be asked about suicidal thoughts at every visit. 

For many, though, the level of trust they have with HCPs makes or breaks whether they discuss their suicidal ideation. Higher ratings of the therapeutic relationship with clinicians are associated with more frequent disclosure. However, the screen-positive group demonstrated higher rates of inaccurate disclosure than the screen-negative group. While this may seem counterintuitive, it is possible that screen-positive individuals did not fully disclose their thoughts on the initial screen, or did not fully disclose the severity of their thoughts during follow-up evaluations. Individuals who disclose suicidal thoughts during initial screening may be ambivalent about disclosure and/or become more concerned about consequences of disclosure as additional evaluation ensues. 

A 2013 study of 34 Operation Enduring Freedom/Operation Iraqi Freedom veterans found that veterans felt trying to suppress and avoid thoughts of suicide was “burdensome and exhausting.” Despite this, they often failed to disclose severe and pervasive suicidal thoughts when screened. Among the reasons was that they perceived the templated computer reminder process as “perfunctory and disrespectful.”

Research has found that HCPs who focuses on building relationships, demonstrates genuineness and empathy, and uses straightforward and understandable language promotes the trust that can result in more honest disclosure of suicidal thoughts. In the “inaccurate disclosure” study, some veterans reported they did not understand the screening questions, or the questions did not make sense to them. This aligns with prior research, which demonstrates that how HCPs and researchers conceptualize suicidal thoughts may not fit with patients’ experiences. A lack of shared terminology, they note, “may confound how we think about ‘under-disclosure,’ such that perhaps patients may not be trying to hide their thoughts so much as not finding screening questions applicable to their unique situations or experiences.”

Veterans at risk of suicide may not share their suicidal ideation with their psychotherapists or may choose not to disclose enough detail to illustrate the depths of those thoughts due to feelings of shame or embarrassment, according to a newly published study. These individuals may view suicidal thoughts as a sign of weakness, fear involuntary hospitalization or prescriptions, or belong to marginalized groups who do not feel comfortable (or safe) to reveal their thoughts or intentions. This can make it difficult for mental health professionals to identify the exact details of a patient’s mindset and provide appropriate care. 

A veteran’s first—and sometimes only—stop may be their primary care practitioner (PCPs) rather than a mental health professional. A review of 40 studies found that although 45% of individuals who died by suicide had contact with PCPs within 1 month of their death, only 19% had contact with mental health services. Studies have also found that veterans disclose suicidal ideation during primary care visits closest to the actual suicide less than half the time.

Patients may have an appointment for medical, but not psychological reasons. In a study conducted at Portland Veterans Affairs Medical Center (VAMC), researchers reviewed the medical records of 112 veterans who died by suicide and had contact with a VAMC within 1 year prior to death. Of those last contacts, 32% were patient-initiated for new or exacerbated medical concerns, and 68% were follow-ups. 

In that study, health care professionals (HCPs) noted that 41 patients (37%) were experiencing emotional distress at the last contact, but 13 of 18 patients (72%) who were assessed for suicidal ideation at their last contact denied such thoughts. The study says this finding “highlights the complexity of addressing suicidal ideation and associated risk factors in health care settings.” Additionally, a number of veterans who died by suicide either did not have suicidal thoughts  at the time of their last contact with HCPs or denied such thoughts even when questioned. 

In 2018, the Veterans Health Administration (VHA) implemented the Suicide Risk Identification Strategy (Risk ID), an evidence-informed assessment that includes initial screening and subsequent evaluation. Veterans receiving VHA care are screened annually for suicidal ideation and behaviors. Most screening takes place in primary care and mental health specialty settings, but timely screening may not be enough to assess who is at risk if the patients aren’t being forthcoming about their thoughts and plans.

A recent cross-sectional national survey examined the frequency of self-reported “inaccurate disclosure” of suicidal ideation during initial screening and subsequent evaluation among 734 VHA patients screened in primary care.

Using the Risk ID process with the Columbia Suicide Severity Rating Scale Screener (C-SSRS), the study asked respondents about their previous suicide screening in 2021. Of the 734 respondents, 306 screened positive and 428 screened negative. One survey item asked about the extent to which veterans had accurately responded to the HCP when asked about suicidal thoughts, while another asked how likely they would discuss when they felt suicidal with their PCP.

The study found that inaccurate disclosure is not uncommon: When asked about suicidal thoughts, about one-fifth of screen-negative participants and two-fifths of screen-positive participants said they responded, “less than very accurately.”

In the screen-positive group, women and those who reported more barriers to care were less likely to discuss feeling suicidal. Veterans who had lower ratings of satisfaction with the screening process, patient-staff communication, and the therapeutic relationship reported being less likely to discuss times they were suicidal. Notably, among C-SSRS-negative patients, Black, American Indian/Alaska Native, Hispanic, Asian, and multiracial veterans were more likely than White veterans to inaccurately report suicidal thoughts. 

This is consistent with studies on medical mistrust and other research suggesting that veterans who have experienced identity-based discrimination may be less inclined to discuss suicidal thoughts with VHA HCPs. A large 2023 study surveyed veterans about why they might hold back such information. One Gulf War-era veteran, a Black woman, had encountered discrimination when filing her VA benefits claim, leading her to feel like the care system was not interested in helping her.

“It’s one of the main reasons why when I do go in, they don’t get an honest response,” she wrote in her survey response. “I feel that you’re not for me, you’re not trying to help me, you don’t wanna help me, and why even go through it, go through the motions it seems. So, I can come in feeling suicidal and I leave out feeling suicidal then.” 

Veterans typically welcome screening for suicidal risk. In a 2023 study, > 90% of veterans reported that it is appropriate to be asked about thoughts of suicide during primary care visits, and about one-half agreed that veterans should be asked about suicidal thoughts at every visit. 

For many, though, the level of trust they have with HCPs makes or breaks whether they discuss their suicidal ideation. Higher ratings of the therapeutic relationship with clinicians are associated with more frequent disclosure. However, the screen-positive group demonstrated higher rates of inaccurate disclosure than the screen-negative group. While this may seem counterintuitive, it is possible that screen-positive individuals did not fully disclose their thoughts on the initial screen, or did not fully disclose the severity of their thoughts during follow-up evaluations. Individuals who disclose suicidal thoughts during initial screening may be ambivalent about disclosure and/or become more concerned about consequences of disclosure as additional evaluation ensues. 

A 2013 study of 34 Operation Enduring Freedom/Operation Iraqi Freedom veterans found that veterans felt trying to suppress and avoid thoughts of suicide was “burdensome and exhausting.” Despite this, they often failed to disclose severe and pervasive suicidal thoughts when screened. Among the reasons was that they perceived the templated computer reminder process as “perfunctory and disrespectful.”

Research has found that HCPs who focuses on building relationships, demonstrates genuineness and empathy, and uses straightforward and understandable language promotes the trust that can result in more honest disclosure of suicidal thoughts. In the “inaccurate disclosure” study, some veterans reported they did not understand the screening questions, or the questions did not make sense to them. This aligns with prior research, which demonstrates that how HCPs and researchers conceptualize suicidal thoughts may not fit with patients’ experiences. A lack of shared terminology, they note, “may confound how we think about ‘under-disclosure,’ such that perhaps patients may not be trying to hide their thoughts so much as not finding screening questions applicable to their unique situations or experiences.”

Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).¹

MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.

MRI Biomarkers in MS

T2-lesions, Chronic Black Holes, and Brain Atrophy

Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.

Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.² T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.³ T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.⁴ A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.⁵

 

Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.⁶ cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.^5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.⁸

Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.⁹

Paramagnetic Rim Lesions

Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.¹⁰ PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.^10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.^12,13 The prevention of PIRA is therefore an unmet treatment need.

Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.¹⁴ The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.¹⁵ CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.^16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.¹⁹ These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.²⁰

PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.^21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.²⁴ Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.^25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.

The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.^27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.^21,22,30

PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.³¹ Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses. 

Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.

Central Vein Sign

A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.³² Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.³³

CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.³⁴ With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.³⁵

MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.³⁵ The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,³⁶ migraines,³⁷ neuromyelitis optica spectrum disorders,^38,39 Susac syndrome,⁴⁰ and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).⁴¹

With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.⁴²

A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.⁴³ Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,⁴⁴ 60% cut off,⁴⁵ and Select 3* or Select 6* methods.⁴⁶ The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.

The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.

Quantitative MRI Techniques

In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.⁴⁷ Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.⁴⁸ A higher value of any of these metrics is associated with a higher degree of tissue injury.

Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.⁴⁸ Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.⁴⁹ SMT generates the apparent axonal volume fraction (V_ax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). V_ax was previously validated in MS as a measure of axonal integrity.⁴⁹

In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).^50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.⁵²Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.⁵² Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.⁵³

Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.⁵⁴ These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,⁵² PSR,⁵³ and V_ax,⁴⁹ investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.⁵⁵

Anticipated Innovations and Challenges

In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.⁵⁶ Another example is multicompartment diffusion imaging, such as standard model imaging,⁵⁷ and neurite orientation dispersion and density imaging,⁵⁸ which considers water as an additional compartment compared with the SMT derived V_ax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.⁵⁹

Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.⁶⁰

Conclusions

MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.

Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).¹

MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.

MRI Biomarkers in MS

T2-lesions, Chronic Black Holes, and Brain Atrophy

Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.

Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.² T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.³ T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.⁴ A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.⁵

 

Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.⁶ cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.^5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.⁸

Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.⁹

Paramagnetic Rim Lesions

Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.¹⁰ PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.^10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.^12,13 The prevention of PIRA is therefore an unmet treatment need.

Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.¹⁴ The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.¹⁵ CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.^16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.¹⁹ These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.²⁰

PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.^21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.²⁴ Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.^25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.

The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.^27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.^21,22,30

PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.³¹ Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses. 

Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.

Central Vein Sign

A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.³² Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.³³

CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.³⁴ With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.³⁵

MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.³⁵ The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,³⁶ migraines,³⁷ neuromyelitis optica spectrum disorders,^38,39 Susac syndrome,⁴⁰ and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).⁴¹

With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.⁴²

A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.⁴³ Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,⁴⁴ 60% cut off,⁴⁵ and Select 3* or Select 6* methods.⁴⁶ The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.

The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.

Quantitative MRI Techniques

In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.⁴⁷ Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.⁴⁸ A higher value of any of these metrics is associated with a higher degree of tissue injury.

Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.⁴⁸ Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.⁴⁹ SMT generates the apparent axonal volume fraction (V_ax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). V_ax was previously validated in MS as a measure of axonal integrity.⁴⁹

In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).^50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.⁵²Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.⁵² Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.⁵³

Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.⁵⁴ These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,⁵² PSR,⁵³ and V_ax,⁴⁹ investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.⁵⁵

Anticipated Innovations and Challenges

In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.⁵⁶ Another example is multicompartment diffusion imaging, such as standard model imaging,⁵⁷ and neurite orientation dispersion and density imaging,⁵⁸ which considers water as an additional compartment compared with the SMT derived V_ax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.⁵⁹

Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.⁶⁰

Conclusions

MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.

Multiple sclerosis (MS) is a complex, chronic immune-mediated disease of the central nervous system characterized by focal inflammation, demyelination, and neurodegeneration. Magnetic resonance imaging (MRI), first incorporated into the McDonald Criteria for the diagnosis of MS in 2001, is an integral tool in the diagnosis, prognosis, and therapeutic monitoring of people with MS (PwMS).¹

MRI research in MS is rapidly expanding and offers insights into the pathophysiology of MS with important implications for the routine clinical care of PwMS. At the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting, the US Department of Veterans Affairs (VA) MS Centers of Excellence hosted an educational symposium highlighting MRI biomarkers in MS, including T2-lesions, chronic black holes (cBHs), brain atrophy, paramagnetic rim lesions (PRLs), and the central vein sign (CVS). The symposium also provided a brief overview of quantitative MRI techniques used to characterize MS lesion severity and research applications of these techniques. This clinical review summarizes the main points of that symposium with the goal of introducing key concepts to federal health care practitioners caring for PwMS.

MRI Biomarkers in MS

T2-lesions, Chronic Black Holes, and Brain Atrophy

Focal immune-mediated inflammation and demyelination in MS may be detected by MRI as hyperintense foci on T2-weighted (T2-w) imaging (eg, T2-w turbo spin echo or T2-w fluid attenuated inversion recovery sequences). These T2-lesions, critical for diagnosing MS, are typically ovoid and occur in the periventricular, juxtacortical, infratentorial spinal cord white matter (Figure 1A). T2-lesion number and volume show some association with disability and optic nerve.

Wattjes et al highlight 2 cases to demonstrate this point: a man aged 52 years with MS for 23 years and a woman aged 50 years with MS for 11 years. Despite having MS for a much shorter duration, the woman had worse disability due to a higher lesion number and volume.² T2-lesion volume also impacts disability progression in PwMS. Gauthier et al compared the probability of progression in 3 women, all of whom were aged 39 years and had MS for 6 years. The profile with highest probability of disability progression had the highest quartile of T2-lesion volume.³ T2-lesion volume over 2 years correlates with worse scores on disability metrics such as the MS functional composite, paced auditory serial addition task, and brain volume.⁴ A 2024 systematic review and meta-analysis demonstrated that T2-lesion volume is significantly correlated with clinical disability in PwMS.⁵

 

Select T2-lesions are also hypointense on T1-w spin echo images and are known as cBHs (Figure 1B). Histologically, T2-lesions with cBHs have more severe architectural disruption than those without cBHs.⁶ cBH number and volume are significantly correlated with disability, regardless of the degree of hypointensity on T1-w imaging.^5,7 A 10-year longitudinal study demonstrated that cBHs were associated with disease progression after 5 years while T2-lesion volume was not, indicating that cBHs may be a more accurate predictor of disability.⁸

Brain atrophy, another imaging biomarker of MS, affects both the cerebral white and gray matter. White matter fraction (the volume of white matter relative to the intracranial compartment volume) and gray matter fraction (the volume of gray matter relative to the intracranial compartment) are significantly lower among PwMS compared with healthy controls. In addition, gray matter fraction is lower among patients with primary and secondary progressive MS compared with those with relapsing-remitting MS, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS). Gray matter fraction is also correlated with several motor and cognitive disability indices.⁹

Paramagnetic Rim Lesions

Neurologic worsening in PwMS occurs by 2 distinct mechanisms: relapse-associated worsening, a stepwise worsening of symptoms due to incomplete recovery following a relapse; and progression independent of relapse activity (PIRA), which is an irreversible neurologic deterioration in the absence of clinical or radiological relapses.¹⁰ PIRA is associated with neurodegeneration and predominates in both primary and secondary progressive MS. However, recent data demonstrated that PIRA may contribute to as much as 50% of disability worsening in relapsing MS and occurs early in the RMS disease course.^10,11 Current high-efficacy disease modifying therapy, such as ocrelizumab, are extraordinarily successful at preventing focal inflammation and relapses but are less effective for preventing the slow march of disability progression characterizing PIRA.^12,13 The prevention of PIRA is therefore an unmet treatment need.

Chronic active lesions (CALs) are an important driver of PIRA. When an acute gadolinium-enhancing lesion develops in PwMS, there are 3 possible fates of this lesion. The lesion may become chronically inactive, remyelinate, or transition to CALs.¹⁴ The histopathologic signature of CALs is compartmentalized, low-grade inflammation behind an intact blood-brain barrier with evidence of both active and chronic components.¹⁵ CALs may be found not only in cerebral white matter but also in the cerebral cortex and spinal cord.^16,17 Combined MRI and histopathological studies have shown that iron-laden microglia/macrophages can be detected by susceptibility-based MRI as a rim of paramagnetic signal surrounding select T2-lesions.¹⁹ These PRLs represent an in vivo imaging biomarker of CAL (Figure 1C). According to the North American Imaging in MS Cooperative (NAIMS) consensus criteria, a PRL must surround at least two-thirds of the outer edge of a T2-lesion, be visible in ≥ 2 consecutive MRI slices, and cannot be contrast enhancing.²⁰

PRLs can be visualized on multiple susceptibility-based imaging methods, including multiecho derived R2*/T2*, phase maps, susceptibility-weighted imaging, and quantitative susceptibility mapping.^21-23 Retrospective analyses have shown no significant differences in sensitivity across these imaging modalities.²⁴ Although first visualized with 7T MRI, PRLs may also be detected by 1.5T and 3T MRI with comparable sensitivities.^25-27 However, there remains a significant knowledge gap regarding the accuracy of each imaging modality. Systematic, prospectively designed studies are needed to ascertain the comparative value of each method.

The presence of PRL is a poor prognostic indicator. PwMS without PRLs have higher levels of disability, are more likely to progress, and demonstrate greater gray matter atrophy and cognitive dysfunction when compared with PwMS with PRLs.^27-29 Lesions with PRL tend to slowly expand, exhibit greater demyelination, and have diminished white matter integrity.^21,22,30

PRLs may also be used as a diagnostic tool. PRLs are highly specific for MS/CIS with a 99.7% specificity and 98.4% positive predictive value, although the sensitivity is limited to 24%.³¹ Taken together, these data indicate that the presence of a PRL substantially increases the likelihood of an MS/CIS diagnosis, whereas the absence of a PRL does not exclude these diagnoses. 

Several unanswered questions remain: Why do select acute MS lesions transition to CALs? How may investigators utilize PRLs as outcome measures in future clinical trials? How should PRLs be incorporated into the routine care of PwMS? As the role of this imaging biomarker is clarified both in the research and clinical settings, clinicians caring for PwMS can expect to increasingly encounter the topic of PRLs in the near future.

Central Vein Sign

A CVS is defined by the presence of a central vessel within a demyelinating plaque (Figure 1D). As early as the 1820s, MS plaques on gross pathology were noted to follow the course of a vessel. Early histological studies reported that up to 91% of MS plaques had a central vessel present.³² Lesion formation is dependent on the movement of lymphocytes and other inflammatory cells from the systemic circulation across the blood brain barrier into the perivascular space, a privileged site where immune cells interact with antigen presenting cells to launch an inflammatory cascade and eventual demyelinating lesion.³³

CVS can be visualized on 1.5T, 3T and 7T MRI. However, 7T MRI is superior to 3T in the detection of CVS, with 85% of MS lesions having CVS visible compared with 45% on 3T.³⁴ With advances in 7T MRI, fluid attenuated inversion recovery and T2* susceptibility, weighted sequences can be overlaid, allowing simultaneous visualization of the vessel and the demyelinating lesion. With higher density of parenchymal veins in the periventricular regions, the CVS is most seen in lesions of this territory but can also be present in juxtacortical, thalamic and infratentorial lesions with decreasing prevalence as these approach the cortex.³⁵

MS lesions are more likely to have CVS than T2 hyperintense white matter lesions of other causes, with a large study reporting 78% of MS lesions were CVS positive. Further, CVS positive lesions can be found across all MS phenotypes including relapsing remitting, primary progressive, and secondary progressive.³⁵ The CVS is also specific to MS lesions and is an effective tool for differentiating MS lesions from other common causes of T2 hyperintense lesions including chronic ischemic white matter disease,³⁶ migraines,³⁷ neuromyelitis optica spectrum disorders,^38,39 Susac syndrome,⁴⁰ and systemic autoimmune diseases (Behcet disease, systemic lupus erythematosus, and antiphospholipid syndrome).⁴¹

With CVS emerging as a promising radiographic biomarker for MS, NAIMS issued a consensus statement on necessary properties of a CVS. These criteria included appearance of a thin hypointense line or small dot, visualized in ≥ 2 perpendicular planes, with diameter < 2 mm, and running partially or entirely through the center of the lesion. They also clarified that lesions < 3 mm, confluent lesions, lesions with multiple vessels present or poorly visualized lesions were excluded.⁴²

A shared CVS definition was a necessary step toward routine use of CVS as a radiographic biomarker and its incorporation in the 2024 revised McDonald criteria.⁴³ Remaining limitations including 7T MRI is primarily available in research settings and the lack of consensus on a diagnostic threshold. There have been many proposed methods, including a 40% cut off,⁴⁴ 60% cut off,⁴⁵ and Select 3* or Select 6* methods.⁴⁶ The goal of each method is to optimize sensitivity and specificity while not compromising efficiency of MRI review for both neurologists and radiologists.

The CVS has significant potential as a radiographic biomarker for MS and may allow the early stages of MS to be differentiated from other common causes of white matter lesions on MRI. However, it remains unclear whether CVS holds prognostic value for patients, if CVS is suggestive of differing underlying pathology, or if the presence of a CVS is dynamic over time. Progress in these areas is anticipated as CVS is incorporated into routine clinical practice.

Quantitative MRI Techniques

In the research setting, several imaging modalities can be used to quantify the degree of microstructural injury in PwMS. The goal of these methods is to identify and quantify myelin and axonal damage, the major drivers of neurodegeneration. Among these methods, diffusion-based imaging is a measure of the amount of diffusion or fluid mobility across the tissues of the brain.⁴⁷ Diffusion-weighted imaging (DWI) yields several parametric maps including axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (Figure 2 A, B, and C). These parametric maps provide information on different directions of water molecules’ movements. Myelin surrounds the axons preventing water molecules diffusion perpendicular to axons (RD) while axonal content prevents water diffusion horizontal to the axons (AD).Thus, AD is considered more specific to axonal injury, whereas RD is specific to myelin content.⁴⁸ A higher value of any of these metrics is associated with a higher degree of tissue injury.

Although sensitive to axonal and myelin injury, AD and RD computed from single b-shell DWI experience several limitations including being affected by nonpathologic factors such as fiber orientation, distribution, and crossing, and by various nonmyelin specific pathologies including fluid accumulation during inflammation, myelin sheath thickness, and axonal intactness.⁴⁸ Several multi b-shell methods have been developed to overcome diffusion imaging limitations. For example, work at the Nashville VA MS Center of Excellence has focused on the use of the multicompartment diffusion MRI with spherical mean technique (SMT). This method removes the orientation dependency of the diffusion MRI signal, increasing the signal-to-noise ratio and reducing biases from fiber undulation, crossing, and dispersion.⁴⁹ SMT generates the apparent axonal volume fraction (V_ax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). V_ax was previously validated in MS as a measure of axonal integrity.⁴⁹

In terms of myelin, several other specific measures have been developed. Magnetization transfer ratio (MTR) is another measure of tissue integrity that has been validated as a measure of tissue injury in MS (Figure 2E).^50,51 Zheng et al found that the percentage of lesions with low MTR was significantly higher among patients whose disease disability progressed compared with patients who did not.⁵²Selective inversion recovery with quantitative magnetization transfer (SIR-qMT) was developed to account for the limitations of MTR, including its sensitivity to edema and axonal density.⁵² Germane to myelin measurements, SIR-qMT generates the macromolecular to free size ratio (PSR). PSR represents the ratio of protons bound to macromolecules (myelin) to free protons (Figure 2F). PSR is considered a marker of myelin integrity, with lower values correlating with disability severity and indicating higher tissue damage and lower myelin content. Previous studies from the Nashville VA MS Center of Excellence validated the use of SIR-qMT among patients with MS, CIS, RIS, and healthy controls.⁵³

Quantitative MRI has several research applications in the field of MS. We demonstrated that PRL harbor a higher degree of myelin injury indicated by PSR compared with rimless lesions.⁵⁴ These MRI techniques are also helpful to investigate tissues surrounding the lesions, called normal appearing white matter (NAWM). Using quantitative MRI techniques such as MTR,⁵² PSR,⁵³ and V_ax,⁴⁹ investigators have demonstrated that NAWM is injured in PwMS, and proximal NAWM may have higher degree of tissue damage compared with distant NAWM.⁵⁵

Anticipated Innovations and Challenges

In the field of quantitative MRI, several new techniques are being adopted. Researchers are developing techniques such as myelin water fraction which evaluates the interaction between water and protons to measure myelin content. This is considered an advancement as it takes into account edema resulting from MS injury.⁵⁶ Another example is multicompartment diffusion imaging, such as standard model imaging,⁵⁷ and neurite orientation dispersion and density imaging,⁵⁸ which considers water as an additional compartment compared with the SMT derived V_ax. For PRL identification, more advanced methodologic techniques are developing such quantitative susceptibility mapping (QSM), which can detect iron deposits that surround the lesions with relatively high sensitivity and specificity of identifying PRL.⁵⁹

Despite these innovations, several challenges remain before possible incorporation into the clinical setting. These limitations include longer scan time, familiarity of clinicians in using these maps, higher financial cost, and the necessity of advanced imaging processing skills. Artificial intelligence is a promising tool that may overcome these challenges through creating automated processing pipelines and developing synthetic maps without the need for additional acquisition.⁶⁰

Conclusions

MRI is the most important tool for diagnosing and treating PwMS. Imaging biomarkers such as T2-lesions, cBHs, brain atrophy, PRLs, and CVS provide insight into the disease’s pathogenesis and are invaluable for the accurate diagnosis and prognostication of MS. Quantitative MRI techniques, while not available in the clinical setting, are important tools for translational research that may help direct the development of future therapeutics. In the near future, clinicians caring for PwMS should expect to encounter these imaging biomarkers more frequently in the clinical setting, especially with the inclusion of PRLs and CVS in the next iteration of the McDonald diagnostic criteria.

AGA leaders came from across the country to Washington, D.C., on Sept. 25 with a major goal in mind: to advocate for gastroenterology with their lawmakers during our annual Advocacy Day. For our leaders, showing up on behalf of their patients is a privilege and an opportunity to represent the specialty with individuals who have a role in dictating health care policy.

In total, 124 members, patient advocates, and AGA staffers met with lawmakers and attended 130 meetings – 70 unique House districts and 60 unique Senate districts – with Republican and Democratic staff.

Our advocacy contingent represented the diversity of the country with 30 states represented from coast-to-coast. No matter the home state, everyone was united in the calls to Congress: to reform prior authorization, increase digestive disease funding, and secure a permanent solution for Medicare physician reimbursement.

As in past years, patient advocates participated alongside GI clinicians and researchers.

Their participation underscored the importance of including diverse voices. As patients with chronic health conditions, they were able to convey how their experiences navigating insurance barriers or managing delays to care as prescribed by their health care provider impacted their well-being and quality of life.

Throughout the day, patient advocates and GIs alike were encouraged by their meetings with congressional staffers. Conversations were constructive, engaging, and meaningful as everyone collaborated on common ground: seeking solutions to ensure GI patients have timely access to care that they need.

Many AGA leaders appreciated the value of being able to unite with colleagues to advocate and share their firsthand experiences in the lab or clinic in meetings with House and Senate staffers.

While Advocacy Day lasts a single day, its value hasn’t diminished. Thanks to the engagement and participation of the more than 100 AGA leaders and patient advocates, we can continue to build positive relationships with influential policymakers and make strides to improve and protect access to GI patient care.

AGA leaders came from across the country to Washington, D.C., on Sept. 25 with a major goal in mind: to advocate for gastroenterology with their lawmakers during our annual Advocacy Day. For our leaders, showing up on behalf of their patients is a privilege and an opportunity to represent the specialty with individuals who have a role in dictating health care policy.

In total, 124 members, patient advocates, and AGA staffers met with lawmakers and attended 130 meetings – 70 unique House districts and 60 unique Senate districts – with Republican and Democratic staff.

Our advocacy contingent represented the diversity of the country with 30 states represented from coast-to-coast. No matter the home state, everyone was united in the calls to Congress: to reform prior authorization, increase digestive disease funding, and secure a permanent solution for Medicare physician reimbursement.

As in past years, patient advocates participated alongside GI clinicians and researchers.

Their participation underscored the importance of including diverse voices. As patients with chronic health conditions, they were able to convey how their experiences navigating insurance barriers or managing delays to care as prescribed by their health care provider impacted their well-being and quality of life.

Throughout the day, patient advocates and GIs alike were encouraged by their meetings with congressional staffers. Conversations were constructive, engaging, and meaningful as everyone collaborated on common ground: seeking solutions to ensure GI patients have timely access to care that they need.

Many AGA leaders appreciated the value of being able to unite with colleagues to advocate and share their firsthand experiences in the lab or clinic in meetings with House and Senate staffers.

While Advocacy Day lasts a single day, its value hasn’t diminished. Thanks to the engagement and participation of the more than 100 AGA leaders and patient advocates, we can continue to build positive relationships with influential policymakers and make strides to improve and protect access to GI patient care.

AGA leaders came from across the country to Washington, D.C., on Sept. 25 with a major goal in mind: to advocate for gastroenterology with their lawmakers during our annual Advocacy Day. For our leaders, showing up on behalf of their patients is a privilege and an opportunity to represent the specialty with individuals who have a role in dictating health care policy.

In total, 124 members, patient advocates, and AGA staffers met with lawmakers and attended 130 meetings – 70 unique House districts and 60 unique Senate districts – with Republican and Democratic staff.

Our advocacy contingent represented the diversity of the country with 30 states represented from coast-to-coast. No matter the home state, everyone was united in the calls to Congress: to reform prior authorization, increase digestive disease funding, and secure a permanent solution for Medicare physician reimbursement.

As in past years, patient advocates participated alongside GI clinicians and researchers.

Their participation underscored the importance of including diverse voices. As patients with chronic health conditions, they were able to convey how their experiences navigating insurance barriers or managing delays to care as prescribed by their health care provider impacted their well-being and quality of life.

Throughout the day, patient advocates and GIs alike were encouraged by their meetings with congressional staffers. Conversations were constructive, engaging, and meaningful as everyone collaborated on common ground: seeking solutions to ensure GI patients have timely access to care that they need.

Many AGA leaders appreciated the value of being able to unite with colleagues to advocate and share their firsthand experiences in the lab or clinic in meetings with House and Senate staffers.

While Advocacy Day lasts a single day, its value hasn’t diminished. Thanks to the engagement and participation of the more than 100 AGA leaders and patient advocates, we can continue to build positive relationships with influential policymakers and make strides to improve and protect access to GI patient care.

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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