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Fed Pract
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gaming
gambling
compulsive behaviors
ammunition
assault rifle
black jack
Boko Haram
bondage
child abuse
cocaine
Daech
drug paraphernalia
explosion
gun
human trafficking
ISIL
ISIS
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Islamic state
mixed martial arts
MMA
molestation
national rifle association
NRA
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pedophilia
poker
porn
pornography
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recreational drug
sex slave rings
slot machine
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Texas hold 'em
UFC
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bunges
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butt
butt fuck
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buttfucked
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cock sucker
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.

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American Hunger Games: Food Insecurity Among the Military and Veterans

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American Hunger Games: Food Insecurity Among the Military and Veterans

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius1

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1

References
  1. Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.

  2. National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm 

  3. Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html

  4. US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security

  5. Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans

  6. Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/

  7. Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584

  8. Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/

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Correspondence: Cynthia Geppert (fedprac@mdedge.com) 

Fed Pract. 2025;42(10). Published online October 15. doi:10.12788/fp.0647

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The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius1

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1

The requisites of government are that there be sufficiency of food, sufficiency of military equipment, and the confidence of the people in their ruler.

Analects by Confucius1

From ancient festivals to modern holidays, autumn has long been associated with the gathering of the harvest. Friends and families come together around tables laden with delicious food to enjoy the pleasures of peace and plenty. During these celebrations, we must never forget that without the strength of the nation’s military and the service of its veterans, this freedom and abundance would not be possible. Our debt of gratitude to the current and former members of the armed services makes the fact that a substantial minority experiences food insecurity not only a human tragedy, but a travesty of the nation’s promise to support those who wear or have worn the uniform.

The National Defense Authorization Act for Fiscal Year 2020 charged the Secretary of Defense to investigate food insecurity among active-duty service members and their dependents.2 The RAND Corporation conducted the assessment and, based on the results of its analysis, made recommendations to reduce hunger among armed forces members and their families.3

The RAND study found that 10% of active-duty military met US Department of Agriculture (USDA) criteria for very low food security; another 15% were classified as having low food security. The USDA defines food insecurity with hunger as “reports of multiple indications of disrupted eating patterns and reduced food intake.” USDA defines low food security as “reports of reduced quality, variety, or desirability of diet. Little or no indication of reduced food intake.”4

As someone who grew up on an Army base with the commissary a short trip from military housing, I was unpleasantly surprised that food insecurity was more common among in-service members living on post. I was even more dismayed to read that a variety of factors constrained 14% of active-duty military experiencing food insecurity to seek public assistance to feed themselves and their families. As with so many health care and social services, (eg, mental health care), those wearing the uniform were concerned that participating in a food assistance program would damage their career or stigmatize them. Others did not seek help, perhaps because they believed they were not eligible, and in many cases were correct: they did not qualify for food banks or food stamps due to receiving other benefits. A variety of factors contribute to periods of food insecurity among military families, including remote or rural bases that lack access to grocery stores or jobs for partners or other family members, and low base military pay.5

Food insecurity is an even more serious concern among veterans who are frequently older and have more comorbidities, often leading to unemployment and homelessness. Feeding America, the nation’s largest organization of community food banks, estimates that 1 in 9 working-age veterans are food insecure.5 US Department of Veterans Affairs (VA) statistics indicate that veterans are 7% more likely to experience food insecurity than other sectors of the population.6 The Veterans Health Administration has recognized that food insecurity is directly related to medical problems already common among veterans, including diabetes, obesity, and depression. Women and minority veterans are the most at risk of food insecurity.7

Recognizing that many veterans are at risk of food insecurity, the US Department of Defense and VA have taken steps to try and reduce hunger among those who serve. In response to the shocking statistic that food insecurity was found in 27% of Iraq and Afghanistan veterans, the VA and Rockefeller Foundation are partnering on the Food as Medicine initiative to improve veteran nutrition as a means of improving nutrition-related health consequences of food insecurity.8

Like many federal practitioners, I was unaware of the food insecurity assistance available to active-duty service members or veterans, or how to help individuals access it. In addition to the resources outlined in the Table, there are many community-based options open to anyone, including veterans and service members. 

I have written columns on many difficult issues in my years as the Editor-in-Chief of Federal Practitioner, but personally this is one of the most distressing editorials I have ever published. That individuals dedicated to defending our rights and protecting our safety should be compelled to go hungry or not know if they have enough money at the end of the month to buy food is manifestly unjust. It is challenging when faced with such a large-scale injustice to think we cannot make a difference, but that resignation or abdication only magnifies this inequity. I have a friend who kept giving back even after they retired from federal service: they volunteered at a community garden and brought produce to the local food bank and helped distribute it. That may seem too much for those still working yet almost anyone can pick up a few items on their weekly shopping trip and donate them to a food drive. 

As we approach Veterans Day, let’s not just express our gratitude to our military and veterans in words but in deeds like feeding the hungry and urging elected representatives to fulfill their commitment to ensure that service members and veterans and their families do not experience food insecurity. Confucian wisdom written in a very distant time and vastly dissimilar context still rings true: there are direct and critical links between food and trust and between hunger and the military.1

References
  1. Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.

  2. National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm 

  3. Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html

  4. US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security

  5. Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans

  6. Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/

  7. Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584

  8. Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/

References
  1. Dawson MM. The Wisdom of Confucius: A Collection of the Ethical Sayings of Confucius and of his disciples. International Pocket Library; 1932.

  2. National Defense Authorization Act for Fiscal Year 2020. 116th Cong (2019), Public Law 116-92. U.S. Government Printing Office. https://www.govinfo.gov/content/pkg/PLAW-116publ92/html/PLAW-116publ92.htm 

  3. Asch BJ, Rennane S, Trail TE, et al. Food insecurity among members of the armed forces and their dependents. RAND Corporation. January 3, 2023. Accessed September 22, 2025. https://www.rand.org/pubs/research_reports/RRA1230-1.html

  4. US Department of Agriculture Economic Research Service. Food Security in the U.S.—Definitions of Food Security. US Department of Agriculture Economic Research Service. January 10, 2025. https://www.ers.usda.gov/topics/food-nutrition-assistance/food-security-in-the-us/definitions-of-food-security

  5. Active military and veteran food insecurity. Feeding America. Accessed September 22, 2025. https://www.feedingamerica.org/hunger-in-america/food-insecurity-in-veterans

  6. Pradun S. Find access to stop food insecurity in your community. VA News. September 19, 2025. Accessed September 22, 2025. https://news.va.gov/142733/find-access-stop-food-insecurity-your-community/

  7. Cohen AJ, Dosa DM, Rudolph JL, et al. Risk factors for veteran food insecurity: findings from a National US Department of Veterans Affairs Food Insecurity Screener. Public Health Nutr. 2022;25:819-828. doi:10.1017/S1368980021004584

  8. Chen C. VA and Rockefeller Foundation collaborate to access food for Veterans. VA News. September 5, 2023. Accessed September 22, 2025. https://news.va.gov/123228/va-rockefeller-foundation-expand-access-to-food/

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Updates in Multiple Sclerosis Imaging

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 (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax 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 Vax,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 Vax. 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.

References
  1. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032

  2. Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y

  3. Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1

  4. Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883

  5. Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007

  6. Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182

  7. Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906

  8. Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0

  9. Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423

  10. Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016

  11. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568

  12. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277

  13. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468

  14. Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255

  15. Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y

  16. Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148

  17. Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876

  18. Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x

  19. Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278

  20. Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013

  21. Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z

  22. Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198

  23. Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338

  24. Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845

  25. Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660

  26. Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777

  27. Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750

  28. Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847

  29. Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  30. Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  31. Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677

  32. Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.

  33. Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024

  34. Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144

  35. Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6

  36. Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630

  37. Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273

  38. Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8

  39. Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259

  40. Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270

  41. Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121

  42. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166

  43. Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4

  44. Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405

  45. Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z

  46. Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383

  47. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y

  48. Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028

  49. Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836

  50. Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304

  51. Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5

  52. Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480

  53. Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511

  54. Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173

  55. Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738

  56. Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645

  57. Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290

  58. Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006

  59. Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707

  60. Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422

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Acknowledgments

The authors thank the organizers of the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting for the opportunity to present this topic to attendees.

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aVanderbilt University Medical Center, Nashville, Tennessee 

bMultiple Sclerosis Center of Excellence-East, Washington, DC 

cUniversity of Maryland School of Medicine, Baltimore

dTennessee Valley Health Care System, Nashville  

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The authors report no actual or potential conflicts of interest in regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. 

Ethics and consent

This project was determined to be exempt from review by the Nashville VA Medical Center Institutional Review Board.

Funding

Support includes the Veterans Health Administration (I01CX002160-01A1: AT, FB) and National MS Society (RG-1901-33190: AT, ZR, CC, FB).

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Correspondence: Francesca Bagnato (francesca.bagnato@va.gov) Fed Pract. 2025;42(10). Published online October 15. doi:10.12788/fp.0620

Acknowledgments

The authors thank the organizers of the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting for the opportunity to present this topic to attendees.

Author affiliations

aVanderbilt University Medical Center, Nashville, Tennessee 

bMultiple Sclerosis Center of Excellence-East, Washington, DC 

cUniversity of Maryland School of Medicine, Baltimore

dTennessee Valley Health Care System, Nashville  

Author disclosures

The authors report no actual or potential conflicts of interest in regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. 

Ethics and consent

This project was determined to be exempt from review by the Nashville VA Medical Center Institutional Review Board.

Funding

Support includes the Veterans Health Administration (I01CX002160-01A1: AT, FB) and National MS Society (RG-1901-33190: AT, ZR, CC, FB).

Author and Disclosure Information

Correspondence: Francesca Bagnato (francesca.bagnato@va.gov) Fed Pract. 2025;42(10). Published online October 15. doi:10.12788/fp.0620

Acknowledgments

The authors thank the organizers of the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting for the opportunity to present this topic to attendees.

Author affiliations

aVanderbilt University Medical Center, Nashville, Tennessee 

bMultiple Sclerosis Center of Excellence-East, Washington, DC 

cUniversity of Maryland School of Medicine, Baltimore

dTennessee Valley Health Care System, Nashville  

Author disclosures

The authors report no actual or potential conflicts of interest in regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. 

Ethics and consent

This project was determined to be exempt from review by the Nashville VA Medical Center Institutional Review Board.

Funding

Support includes the Veterans Health Administration (I01CX002160-01A1: AT, FB) and National MS Society (RG-1901-33190: AT, ZR, CC, FB).

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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 (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax 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 Vax,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 Vax. 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 (Vax), which is a direct measure of axonal integrity with lower values indicating lower axonal content and higher tissue destruction (Figure 2D). Vax 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 Vax,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 Vax. 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.

References
  1. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032

  2. Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y

  3. Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1

  4. Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883

  5. Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007

  6. Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182

  7. Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906

  8. Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0

  9. Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423

  10. Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016

  11. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568

  12. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277

  13. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468

  14. Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255

  15. Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y

  16. Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148

  17. Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876

  18. Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x

  19. Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278

  20. Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013

  21. Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z

  22. Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198

  23. Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338

  24. Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845

  25. Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660

  26. Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777

  27. Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750

  28. Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847

  29. Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  30. Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  31. Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677

  32. Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.

  33. Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024

  34. Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144

  35. Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6

  36. Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630

  37. Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273

  38. Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8

  39. Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259

  40. Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270

  41. Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121

  42. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166

  43. Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4

  44. Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405

  45. Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z

  46. Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383

  47. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y

  48. Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028

  49. Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836

  50. Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304

  51. Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5

  52. Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480

  53. Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511

  54. Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173

  55. Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738

  56. Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645

  57. Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290

  58. Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006

  59. Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707

  60. Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422

References
  1. McDonald WI, Compston A, Edan G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121-127. doi:10.1002/ana.1032

  2. Wattjes MP, Steenwijk MD, Stangel M. MRI in the diagnosis and monitoring of multiple sclerosis: an update. Clin Neuroradiol. 2015;25:157-165. doi:10.1007/s00062-015-0430-y

  3. Gauthier SA, Mandel M, Guttmann CR, et al. Predicting short-term disability in multiple sclerosis. Neurology. 2007;68:2059-2065.doi:10.1212/01.wnl.0000264890.97479.b1

  4. Rudick RA, Lee JC, Simon J, Fisher E. Significance of T2 lesions in multiple sclerosis: a 13-year longitudinal study. Ann Neurol. 2006;60:236-242. doi:10.1002/ana.20883

  5. Nabizadeh F, Zafari R, Mohamadi M, et al. MRI features and disability in multiple sclerosis: a systematic review and meta-analysis. J Neuroradiol. 2024;51:24-37. doi:10.1016/j.neurad.2023.11.007

  6. Bagnato F, Jeffries N, Richert ND, et al. Evolution of T1 black holes in patients with multiple sclerosis imaged monthly for 4 years. Brain. 2003;126:1782-1789. doi:10.1093/brain/awg182

  7. Jacobsen C, Hagemeier J, Myhr KM, et al. Brain atrophy and disability progression in multiple sclerosis patients: a 10-year follow-up study. J Neurol Neurosurg Psychiatry. 2014;85:1109-1115. doi:10.1136/jnnp-2013-306906

  8. Rovaris M, Gass A, Bammer R, et al. Diffusion MRI in multiple sclerosis. Neurology. 2005;65:1526-1532. doi:10.1212/01.wnl.0000184471.83948.e0

  9. Fisniku LK, Chard DT, Jackson JS, et al. Gray matter atrophy is related to long-term disability in multiple sclerosis. Ann Neurol. 2008;64:247-254. doi:10.1002/ana.21423

  10. Lublin FD, Häring DA, Ganjgahi H, et al. How patients with multiple sclerosis acquire disability. Brain. 2022;145:3147-3161. doi:10.1093/brain/awac016

  11. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77:1132-1140. doi:10.1001/jamaneurol.2020.1568

  12. Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376:221-234. doi:10.1056/NEJMoa1601277

  13. Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376:209-220. doi:10.1056/NEJMoa1606468

  14. Prineas JW, Kwon EE, Cho ES, et al. Immunopathology of secondary-progressive multiple sclerosis. Ann Neurol. 2001;50:646-657. doi:10.1002/ana.1255

  15. Kuhlmann T, Ludwin S, Prat A, Antel J, Brück W, Lassmann H. An updated histological classification system for multiple sclerosis lesions. Acta Neuropathol. 2017;133:13-24. doi:10.1007/s00401-016-1653-y

  16. Pitt D, Boster A, Pei W, et al. Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging. Arch Neurol. 2010;67:812-818. doi:10.1001/archneurol.2010.148

  17. Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Mult Scler. 2009;15:180-188. doi:10.1177/1352458508096876

  18. Lassmann H, Brück W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 2007;17:210-218. doi:10.1111/j.1750-3639.2007.00064.x

  19. Bagnato F, Hametner S, Yao B, et al. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134:3602-3615. doi:10.1093/brain/awr278

  20. Bagnato F, Sati P, Hemond CC, et al. Imaging chronic active lesions in multiple sclerosis: a consensus statement. Brain. 2024;147:2913-2933. doi:10.1093/brain/awae013

  21. Dal-Bianco A, Grabner G, Kronnerwetter C, et al. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017;133:25-42. doi:10.1007/s00401-016-1636-z

  22. Absinta M, Sati P, Schindler M, et al. Persistent 7-tesla phase rim predicts poor outcome in new multiple sclerosis patient lesions. J Clin Invest. 2016;126:2597-2609. doi:10.1172/JCI86198

  23. Gillen KM, Mubarak M, Park C, et al. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021;8:877-886. doi:10.1002/acn3.51338

  24. Ng Kee Kwong KC, Mollison D, Meijboom R, et al. The prevalence of paramagnetic rim lesions in multiple sclerosis: a systematic review and meta-analysis. PLoS One. 2021;16:e0256845. doi:10.1371/journal.pone.0256845

  25. Absinta M, Sati P, Fechner A, et al. Identification of chronic active multiple sclerosis lesions on 3T MRI. AJNR Am J Neuroradiol. 2018;39:1233-1238. doi:10.3174/ajnr.A5660

  26. Hemond CC, Reich DS, Dundamadappa SK. Paramagnetic rim lesions in multiple sclerosis: comparison of visualization at 1.5-T and 3-T MRI. AJR Am J Roentgenol. 2022;219:120-131. doi:10.2214/AJR.21.26777

  27. Altokhis AI, Hibbert AM, Allen CM, et al. Longitudinal clinical study of patients with iron rim lesions in multiple sclerosis. Mult Scler. 2022;28:2202-2211. doi:10.1177/13524585221114750

  28. Choi S, Lake S, Harrison DM. Evaluation of the blood-brain barrier, demyelination, and neurodegeneration in paramagnetic rim lesions in multiple sclerosis on 7 tesla MRI. J Magn Reson Imaging. 2024;59:941-951. doi:10.1002/jmri.28847

  29. Kazimuddin HF, Wang J, Hernandez B, et al. Paramagnetic rim lesions and their relationship with neurodegeneration and clinical disability at the time of multiple sclerosis diagnosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  30. Rohm Z, Koch C, Kazimuddin H, et al. Longitudinal characterization of paramagnetic rim lesions in early multiple sclerosis. Poster presented at: 2024 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum; February 26-March 2; West Palm Beach, FL.

  31. Meaton I, Altokhis A, Allen CM, et al. Paramagnetic rims are a promising diagnostic imaging biomarker in multiple sclerosis. Mult Scler. 2022;28:2212-2220. doi:10.1177/13524585221118677

  32. Fog T. On the vessel-plaque relationships in the brain in multiple sclerosis. Acta Neurol Scand Suppl. 1964;40:9-15.

  33. Ineichen BV, Okar SV, Proulx ST, et al. Perivascular spaces and their role in neuroinflammation. Neuron. 2022;110:3566-3581. doi:10.1016/j.neuron.2022.10.024

  34. Tallantyre EC, Morgan PS, Dixon JE, et al. A comparison of 3T and 7T in the detection of small parenchymal veins within MS lesions. Invest Radiol. 2009;44:491-494. doi:10.1097/RLI.0b013e3181b4c144

  35. Kilsdonk ID, Lopez-Soriano A, Kuijer JP, et al. Morphological features of MS lesions on FLAIR* at 7 T and their relation to patient characteristics. J Neurol. 2014;261:1356-1364. doi:10.1007/s00415-014-7351-6

  36. Tallantyre EC, Dixon JE, Donaldson I, et al. Ultra-high-field imaging distinguishes MS lesions from asymptomatic white matter lesions. Neurology. 2011;76:534-539. doi:10.1212/WNL.0b013e31820b7630

  37. Solomon AJ, Schindler MK, Howard DB, et al. “Central vessel sign” on 3T FLAIR* MRI for the differentiation of multiple sclerosis from migraine. Ann Clin Transl Neurol. 2015;3:82-87. doi:10.1002/acn3.273

  38. Sinnecker T, Dörr J, Pfueller CF, et al. Distinct lesion morphology at 7-T MRI differentiates neuromyelitis optica from multiple sclerosis. Neurology. 2012;79:708-714. doi:10.1212/WNL.0b013e3182648bc8

  39. Kister I, Herbert J, Zhou Y, Ge Y. Ultrahigh-field MR (7 T) imaging of brain lesions in neuromyelitis optica. Mult Scler Int. 2013;2013:398259. doi:10.1155/2013/398259

  40. Wuerfel J, Sinnecker T, Ringelstein EB, et al. Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis. Mult Scler. 2012;18:1592-1599. doi:10.1177/1352458512441270

  41. Massacesi L. Perivenular distribution of white matter lesions evaluated by MRI can differentiate MS lesions from inflammatory small vessel diseases. Eur J Neurol. 2016;23:86. doi:10.1212/WNL.86.16_supplement.P6.121

  42. Sati P, Oh J, Constable RT, et al. The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative. Nat Rev Neurol. 2016;12:714-722. doi:10.1038/nrneurol.2016.166

  43. Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24:850-865. doi:10.1016/S1474-4422(25)00270-4

  44. Mistry N, Dixon J, Tallantyre E, et al. Central veins in brain lesions visualized with high-field magnetic resonance imaging: a pathologically specific diagnostic biomarker for inflammatory demyelination in the brain. JAMA Neurol. 2013;70:623-628. doi:10.1001/jamaneurol.2013.1405

  45. Campion T, Smith RJP, Altmann DR, et al. FLAIR* to visualize veins in white matter lesions: a new tool for the diagnosis of multiple sclerosis? Eur Radiol. 2017;27:4257-4263. doi:10.1007/s00330-017-4822-z

  46. Solomon AJ, Watts R, Ontaneda D, et al. Diagnostic performance of central vein sign for multiple sclerosis with a simplified three-lesion algorithm. Mult Scler. 2018;24:750-757. doi:10.1177/1352458517726383

  47. Cercignani M, Bozzali M, Iannucci G, Comi G, Filippi M. Intra-voxel and inter-voxel coherence in patients with multiple sclerosis assessed using diffusion tensor MRI. J Neurol. 2002;249:875-883. doi:10.1007/s00415-002-0752-y

  48. Song SK, Yoshino J, Le TQ, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-140. doi:10.1016/j.neuroimage.2005.01.028

  49. Bagnato F, Franco G, Li H, et al. Probing axons using multi-compartmental diffusion in multiple sclerosis. Ann Clin Transl Neurol. 2019;6:1595-1605. doi:10.1002/acn3.50836

  50. Filippi M, Cercignani M, Inglese M, et al. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56:304-311. doi:10.1212/wnl.56.3.304

  51. Bagnato F. Clinical application of magnetization transfer imaging. In: Advanced Neuro MR Techniques and Applications. Elsevier; 2022:403-417. doi:10.1016/B978-0-12-822479-3.00041-5

  52. Zheng Y, Lee JC, Rudick R, Fisher E. Long-term magnetization transfer ratio evolution in multiple sclerosis white matter lesions. J Neuroimaging. 2018;28:191-198. doi:10.1111/jon.12480

  53. Bagnato F, Hametner S, Franco G, et al. Selective inversion recovery quantitative magnetization transfer brain MRI at 7T: clinical and postmortem validation in multiple sclerosis. J Neuroimaging. 2018;28:380-388. doi:10.1111/jon.12511

  54. Clarke MA, Cheek R, Hernandez B, et al. Paramagnetic rim lesions and the central vein sign: characterizing multiple sclerosis imaging markers. J Neuroimaging. 2024;34:86-94. doi:10.1111/jon.13173

  55. Clarke MA, Lakhani DA, Wen S, et al. Perilesional neurodegenerative injury in multiple sclerosis: relation to focal lesions and impact on disability. Mult Scler Relat Disord. 2021;49:102738. doi:10.1016/j.msard.2021.102738

  56. Laule C, Moore GRW. Myelin water imaging to detect demyelination and remyelination and its validation in pathology. Brain Pathol. 2018;28:750-764. doi:10.1111/bpa.12645

  57. Coelho S, Baete SH, Lemberskiy G, et al. Reproducibility of the standard model of diffusion in white matter on clinical MRI systems. Neuroimage. 2022;257:119290. doi:10.1016/j.neuroimage.2022.119290

  58. Novikov DS, Veraart J, Jelescu IO, et al. Rotationally-invariant mapping of scalar and orientational metrics of neuronal microstructure with diffusion MRI. Neuroimage. 2018;174:518-538. doi:10.1016/j.neuroimage.2018.03.006

  59. Langkammer C, Liu T, Khalil M, et al. Quantitative susceptibility mapping in multiple sclerosis. Radiology. 2013;267:551-559. doi:10.1148/radiol.12120707

  60. Collorone S, Coll L, Lorenzi M, et al. Artificial intelligence applied to MRI data to tackle key challenges in multiple sclerosis. Mult Scler. 2024;30:767-784. doi:10.1177/13524585241249422

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Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System

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Impact of Retroactive Application of Updated Surveillance Guidelines on Endoscopy Center Capacity at a Large VA Health Care System

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 



This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

References
  1. Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014

  2. Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360

  3. Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809

  4. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238

  5. Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082

  6. Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033

  7. Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1

  8. Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020

  9. Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027

  10. Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230

  11. Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.

  12. Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x

  13. Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130

  14. Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460

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Correspondence: Ravy Vajravelu (ravy.vajravelu@pitt.edu) Fed Pract. 2025;42(10). Published online October 17. doi:10.12788/fp.0628

Author affiliations

aUniversity of Pittsburgh School of Medicine, Pennsylvania

bVeterans Affairs Pittsburgh Healthcare System, Pennsylvania

cCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

Author disclosures

All authors except Dr. Sun are employees of the US Department of Veterans Affairs. The authors report no other actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

This project was conducted to fulfill a facility mandate to increase endoscopy capacity. Approval for publication of clinical operations activity was obtained from the Veterans Affairs Pittsburgh Healthcare System facility director.

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Correspondence: Ravy Vajravelu (ravy.vajravelu@pitt.edu) Fed Pract. 2025;42(10). Published online October 17. doi:10.12788/fp.0628

Author affiliations

aUniversity of Pittsburgh School of Medicine, Pennsylvania

bVeterans Affairs Pittsburgh Healthcare System, Pennsylvania

cCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

Author disclosures

All authors except Dr. Sun are employees of the US Department of Veterans Affairs. The authors report no other actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

This project was conducted to fulfill a facility mandate to increase endoscopy capacity. Approval for publication of clinical operations activity was obtained from the Veterans Affairs Pittsburgh Healthcare System facility director.

Author and Disclosure Information

Correspondence: Ravy Vajravelu (ravy.vajravelu@pitt.edu) Fed Pract. 2025;42(10). Published online October 17. doi:10.12788/fp.0628

Author affiliations

aUniversity of Pittsburgh School of Medicine, Pennsylvania

bVeterans Affairs Pittsburgh Healthcare System, Pennsylvania

cCorporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania

Author disclosures

All authors except Dr. Sun are employees of the US Department of Veterans Affairs. The authors report no other actual or potential conflicts of interest with regard to this article.

Disclaimer

The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

This project was conducted to fulfill a facility mandate to increase endoscopy capacity. Approval for publication of clinical operations activity was obtained from the Veterans Affairs Pittsburgh Healthcare System facility director.

Article PDF
Article PDF

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 



This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

In 2020, the US Multi-Society Task Force (USMSTF) on Colorectal Cancer (CRC) increased the recommended colon polyp surveillance interval for 1 to 2 subcentimeter tubular adenomas from 5 to 10 years to 7 to 10 years.1 This change was prompted by emerging research indicating that rates of CRC and advanced neoplasia among patients with a history of only 1 to 2 subcentimeter tubular adenomas are lower than initially estimated.2,3 This extension provides an opportunity to increase endoscopy capacity and improve access to colonoscopies by retroactively applying the 2020 guidelines to surveillance interval recommendations made before their introduction. For example, based on the updated guidelines, patients previously recommended to undergo colon polyp surveillance colonoscopy 5 years after an index colonoscopy could extend their surveillance interval by 2 to 5 years. Increasing endoscopic capacity could address the growing demand for colonoscopies from new screening guidelines that reduced the age of initial CRC screening from 50 years to 45 years and the backlog of procedures due to COVID-19 restrictions.4

As part of a project to increase endoscopic capacity at the US Department of Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS), this study assessed the potential impact of retroactively applying the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity. These results may be informative for other VA and private-sector health care systems seeking to identify strategies to improve endoscopy capacity.

Methods

VAPHS is an integrated health care system in the Veterans Health Administration (VHA) serving 85,000 patients across 8 health care institutions in Pennsylvania, Ohio, and West Virginia. VAPHS manages colorectal screening recommendations for patients receiving medical care in the health care system regardless of whether their prior colonoscopy was performed at VAPHS or external facilities. The VA maintains a national CRC screening and surveillance electronic medical record reminder that prompts health care practitioners to order colon polyp surveillance based on interval recommendations from the index colonoscopy. This study reviewed all patients from the VAPHS panel with a reminder to undergo colonoscopy for screening for CRC or surveillance of colon polyps within 12 months from September 1, 2022.

Among patients with a reminder, 3 investigators reviewed index colonoscopy and pathology reports to identify CRC risk category, colonoscopy indication, procedural quality, and recommended repeat colonoscopy interval. Per the USMSTF guidelines, patients with incomplete colonoscopy or pathology records, high-risk indications (ie, personal history of inflammatory bowel disease, personal history of CRC, or family history of CRC), or inadequate bowel preparation (Boston Bowel Preparation Score < 6) were excluded. Additionally, patients who had CRC screening or surveillance discontinued due to age or comorbidities, had completed a subsequent follow-up colonoscopy, or were deceased at the time of review were excluded.

Retroactive Interval Reclassification

Among eligible patients, this study compared the repeat colonoscopy interval recommended by the prior endoscopist with those from the 2020 USMSTF guidelines. In cases where the interval was documented as a range of years, the lower end was considered the recommendation. Similarly, the lower end of the range from the 2020 USMSTF guidelines was used for the reclassified surveillance interval. Years extended per patient were quantified relative to September 1, 2023 (ie, 1 year after the review date). For example, if the index colonoscopy was completed on September 1, 2016, the initial surveillance recommendation was 5 years, and the reclassified recommendation was 7 years, the interval extension beyond September 1, 2023, was 0 years.

Furthermore, because index surveillance recommendations are not always guideline concordant, the years extended per patient were calculated by harmonizing the index endoscopist’s recommendations with the guidelines at the time of the index colonoscopy.5 For example, if the index colonoscopy was completed on September 1, 2018, and the endoscopist recommended a 5-year follow-up for a patient with average risk for CRC, adequate bowel preparation, and no colorectal polyps, that patient is eligible to extend their colonoscopy to September 1, 2028, based on guideline recommendations at the time of index endoscopy recommending that the next colonoscopy occur in 10 years. In this analysis the 2012 USMSTF guidelines were applied to all index colonoscopies completed in 2021 or earlier to allow time for adoption of the 2020 guidelines. 



This project fulfilled a facility mandate to increase capacity to conduct endoscopic procedures. Institutional review board approval was not required by VAPHS policy relating to clinical operations projects. Approval for publication of clinical operations activity was obtained from the VAPHS facility director.

Results

Within 1 year of the September 1, 2022, review date, 637 patients receiving care at VAPHS had clinical reminders for an upcoming colonoscopy. Of these, 54 (8.4%) were already up to date or were deceased at the time of review. Of the 583 eligible patients, 96% were male, the median age was 74 years, the median index colonoscopy year was 2016, and 178 (30.5%) had an average-risk CRC screening indication at the index colonoscopy (Table).

Of the 583 patients due for colonoscopy, 331 (56.7%) had both colonoscopy and pathology reports available. The majority of those with incomplete records had the index colonoscopy completed outside VAPHS. Among these patients, 222 (67.0%) had adequate bowel preparation. Of those with adequate bowel preparation, 43 were not eligible for interval extension because of high-risk conditions and 13 were not eligible because there was no index surveillance interval recommendation from the index endoscopist. Of the patients due for colonoscopy, 166 (28.4%) were potentially eligible for surveillance interval extension (Figure).  

Sixty-five (39.2%) of the 166 patients had 1 to 2 subcentimeter tubular adenomas on their index colonoscopy. Sixty-two patients were eligible for interval extension to 7 years, but this only resulted in ≥ 1 year of extension beyond the review date for 36 (6% of all 583 patients due for colonoscopy). The 36 patients were extended 63 years. By harmonizing the index endoscopists’ surveillance interval recommendation with the guideline at the time of the index colonoscopy, 29 additional patients could have their colonoscopy extended by ≥ 1 year. Harmonization extended colonoscopy intervals by 93 years. Retroactively applying the 2020 USMSTF polyp surveillance guidelines and harmonizing recommendations to guidelines extended the time of index colonoscopy by 153 years.

Discussion

With retroactive application of the 2020 USMSTF polyp surveillance guidelines, 6% of patients due for an upcoming colonoscopy could extend their follow-up by ≥ 1 year by extending the surveillance interval for 1 to 2 subcentimeter tubular adenomas to 7 years. An additional 5% of patients could extend their interval by harmonizing the index endoscopist’s interval recommendation with polyp surveillance guidelines at the time of the index colonoscopy. These findings are consistent with the results of 2 studies that demonstrated that about 14% of patients due for colonoscopy could have their interval extended.6,7 The current study enhances those insights by separating the contribution of 2020 USMSTF polyp surveillance guidelines from the contribution of harmonizing surveillance intervals with guidelines for other polyp histologies. This study found that there is an opportunity to improve endoscopic capacity by harmonizing recommendations with guidelines. This complements a 2023 study showing that even when knowledgeable about guidelines, clinicians do not necessarily follow recommendations.8 While this and previous research have identified that 11% to 14% of patients are eligible for extension, these individuals would also have to be willing to have their polyp surveillance intervals extended for there to be a real-world impact on endoscopic capacity. A 2024 study found that only 19% to 37% of patients with 1 to 2 small tubular adenomas were willing to have polyps surveillance interval extension.9 This suggests the actual effect on capacity may be even lower than reported.

Limitations

The overall impact of the 2020 USMSTF polyp surveillance guidelines on endoscopic capacity was blunted by the high prevalence of incomplete index colonoscopy records among the study population. Without data on bowel preparation quality or procedure indications, this study could not assess whether 43% of patients were eligible for surveillance interval extension. Most index colonoscopies with incomplete documentation were completed at community-care gastroenterology facilities. This high rate of incomplete documentation is likely generalizable to other VA health care systems—especially in the era of the Veterans Access, Choice, and Accountability Act of 2014, which increased veteran access to non-VA community care.10 Veterans due for colon polyp surveillance colonoscopies are more likely to have had their prior colonoscopy in community care compared with prior eras.11 Furthermore, because the VHA is among the most established integrated health care systems offering primary and subspecialty care in the US, private sector health care systems may have even greater rates of care fragmentation for longitudinal CRC screening and colon polyp surveillance, as these systems have only begun to regionally integrate recently.12,13

Another limitation is that nearly one-third of the individuals with documentation had inadequate bowel preparation for surveillance recommendations. This results in shorter surveillance follow-up colonoscopies and increases downstream demand for future colonoscopies. The low yield of extending colon polyp surveillance interval in this study emphasizes that improved efforts to obtain colonoscopy and pathology reports from community care, right-sizing the colon polyp surveillance intervals recommended by endoscopists, and improving quality of bowel preparation could have downstream health care system benefits in the future. These efforts could increase colonoscopy capacity at VA health care systems, thereby shortening colonoscopy wait times, decreasing fragmentation of care, and increasing the number of veterans who receive high-quality colonoscopies at VA health care systems.14

Conclusions

Eleven percent of patients in this study due for a colonoscopy could extend their follow-up by ≥ 1 year. About half of these extensions were directly due to the 2020 USMSTF polyp surveillance interval extension for 1 to 2 subcentimeter tubular adenomas. The rest resulted from harmonizing recommendations with guidelines at the time of the procedure. To determine whether retroactively applying polyp surveillance guidelines to follow-up interval recommendations will result in improved endoscopic capacity, health care system administrators should consider the degree of CRC screening care fragmentation in their patient population. Greater long-term gains in endoscopic capacity may be achieved by proactively supporting endoscopists in making guideline-concordant screening recommendations at the time of colonoscopy.

References
  1. Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014

  2. Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360

  3. Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809

  4. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238

  5. Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082

  6. Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033

  7. Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1

  8. Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020

  9. Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027

  10. Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230

  11. Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.

  12. Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x

  13. Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130

  14. Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460

References
  1. Gupta S, Lieberman D, Anderson JC, et al. Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastrointest Endosc. 2020;91:463-485. doi:10.1016/j.gie.2020.01.014

  2. Dubé C, Yakubu M, McCurdy BR, et al. Risk of advanced adenoma, colorectal cancer, and colorectal cancer mortality in people with low-risk adenomas at baseline colonoscopy: a systematic review and meta-analysis. Am J Gastroenterol. 2017;112:1790-1801. doi:10.1038/ajg.2017.360

  3. Click B, Pinsky PF, Hickey T, Doroudi M, Shoen RE. Association of colonoscopy adenoma findings with long-term colorectal cancer incidence. JAMA. 2018;319:2021-2031. doi:10.1001/jama.2018.5809

  4. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA. 2021;325:1965-1977. doi:10.1001/jama.2021.6238

  5. Djinbachian R, Dubé AJ, Durand M, et al. Adherence to post-polypectomy surveillance guidelines: a systematic review and meta-analysis. Endoscopy. 2019;51:673-683. doi:10.1055/a-0865-2082

  6. Gawron AJ, Kaltenbach T, Dominitz JA. The impact of the coronavirus disease-19 pandemic on access to endoscopy procedures in the VA healthcare system. Gastroenterology. 2020;159:1216-1220.e1. doi:10.1053/j.gastro.2020.07.033

  7. Xiao AH, Chang SY, Stevoff CG, Komanduri S, Pandolfino JE, Keswani RN. Adoption of multi-society guidelines facilitates value-based reduction in screening and surveillance colonoscopy volume during COVID-19 pandemic. Dig Dis Sci. 2021;66:2578-2584. doi:10.1007/s10620-020-06539-1

  8. Dong J, Wang LF, Ardolino E, Feuerstein JD. Real-world compliance with the 2020 U.S. Multi-Society Task Force on Colorectal Cancer polypectomy surveillance guidelines: an observational study. Gastrointest Endosc. 2023;97:350-356.e3. doi:10.1016/j.gie.2022.08.020

  9. Lee JK, Koripella PC, Jensen CD, et al. Randomized trial of patient outreach approaches to de-implement outdated colonoscopy surveillance intervals. Clin Gastroenterol Hepatol. 2024;22:1315-1322.e7. doi:10.1016/j.cgh.2023.12.027

  10. Veterans Access, Choice, and Accountability Act of 2014, HR 3230, 113th Cong (2014). Accessed September 8, 2025. https://www.congress.gov/bill/113th-congress/house-bill/3230

  11. Dueker JM, Khalid A. Performance of the Veterans Choice Program for improving access to colonoscopy at a tertiary VA facility. Fed Pract. 2020;37:224-228.

  12. Oliver A. The Veterans Health Administration: an American success story? Milbank Q. 2007;85:5-35. doi:10.1111/j.1468-0009.2007.00475.x

  13. Furukawa MF, Machta RM, Barrett KA, et al. Landscape of health systems in the United States. Med Care Res Rev. 2020;77:357-366. doi:10.1177/1077558718823130

  14. Petros V, Tsambikos E, Madhoun M, Tierney WM. Impact of community referral on colonoscopy quality metrics in a Veterans Affairs Medical Center. Clin Transl Gastroenterol. 2022;13:e00460. doi:10.14309/ctg.0000000000000460

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A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation

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A Case Report of Unanticipated Difficult Intubation Due to Posterior Tracheal Angulation

Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

References
  1. Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797 

  2. Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8 

  3. Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100

  4. Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824

  5. Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386

  6. Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x

  7. De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2

  8. Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x

  9. Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6

  10. Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005

  11. Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9

  12. Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239

  13. Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06

  14. Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

This manuscript adheres to CARE guidelines. A waiver of patient consent was obtained from the Human Research Protection Program at the Veterans Affairs Puget Sound Health Care System. No potentially identifying information was included in the manuscript.

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Correspondence: Vivek Arora (varora2@uw.edu) Fed Pract. 2025;42(10). Published online October 15. doi:10.12788/fp.0633

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bVeterans Affairs Puget Sound Health Care System, Seattle, Washington

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The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.

Ethics and consent

This manuscript adheres to CARE guidelines. A waiver of patient consent was obtained from the Human Research Protection Program at the Veterans Affairs Puget Sound Health Care System. No potentially identifying information was included in the manuscript.

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Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

Tracheal deviation mostly occurs from mechanical compression of the trachea, and can be caused by a variety of clinical conditions, including trauma,¹ pharyngeal abscess,² neck hematoma,³ thyroid enlargement,4 and kyphoscoliosis.5 These conditions often result in lateral tracheal deviation, which can be associated with tracheal compression and reduction in tracheal caliber.

Anterior-posterior (A-P) tracheal deviation has rarely been reported. Kyphoscoliosis, scarring after a tracheostomy, or innominate vein compression are probable causes of A-P tracheal deviation and can be associated with tracheal narrowing and vascular fistula formation. This report describes a case of difficult endotracheal tube (ETT) advancement secondary to unexpected acute posterior tracheal deviation encountered during cardiopulmonary resuscitation (CPR). A waiver of patient consent was obtained from the Human Research Protection Program at the US Department of Veterans Affairs (VA) Puget Sound Health Care System.

Case Presentation

A 50-year-old male with a history of chronic cerebral venous sinus thrombosis and taking enoxaparin, presented to the emergency department for recurrent headaches. He experienced sudden cardiac arrest, and CPR in the form of chest compression and bag mask ventilation was immediately initiated. With the patient's head in an extended position and using a video laryngoscope, a Cormack–Lehane grade 1 view of the glottic opening was obtained and the trachea was intubated with an 8 mm (internal diameter) polyvinyl chloride ETT. Tracheal intubation was confirmed by utilizing continuous EtCO2 monitoring. The ETT was secured at 22 cm measured at the teeth.

After about 40 minutes of CPR, spontaneous circulation restarted and a portable A-P chest X-ray with the head in a neutral position indicated the ETT tip was at the level of the first rib (Figure 1). This finding, along with a persistent air leak, prompted blind advancement of the ETT to 26 cm at the teeth, but resistance to advancement was noted. A subsequent chest computed tomography (CT) with the head in a neutral position revealed the ETT remained inappropriately positioned with the tip measured 8.2 cm above the carina (Figure 2A). Concurrently, a sagittal CT view demonstrated significant posterior deviation of the mid and lower trachea. This deviation was determined to be the most likely cause of the difficulty encountered in advancing the ETT. No masses or lesions contributing to the acute tracheal angulation could be identified. Comparing CT imaging from 2 months prior, the trachea was of normal caliber and ordinarily aligned with the vertebral column (Figure 2B).

With the patient in Fowler position with the head midline, a flexible fiber-optic bronchoscopy was performed. Acute, almost 90-degree tracheal angulation was encountered and navigated by retroflexion of the flexible bronchoscope. Once the posterior tracheal wall was encountered, retroflexion was relaxed and the carina was visualized. The bronchoscope tip was placed near the carina, and the ETT was advanced over the fiber-optic bronchoscope to terminate 3 cm above the carina. A subsequent chest X-ray confirmed appropriate ETT position (Figure 3).

Discussion

Tracheal deviation in the A-P dimension resulting in difficult tracheal intubation has rarely been reported. Previous reports have described anatomical lesions contributing to similar tracheal deviation, such as retro-tracheal thyroid tissue, pronounced cervical lordosis, and severe kyphoscoliosis with destructive cervical fusion.5-8 In a study of the anatomical correlation of double lumen tube placement while using positron emission tomography CT, Cameron et al evaluated the size and angulation of the glottis and proximal trachea using calibrated CT measurements and an online digital protractor and note nearly perfect alignment of the pharynx and glottis.9 However, the trachea turned posteriorly relative to the glottis, resulting in an overall posterior angle of the proximal trachea compared to the glottis of 30.4 to 50.1 degrees, with no sex differences. The need to maneuver similar proximal tracheal angulation during endotracheal intubation has been reported as a cause of difficult intubation.10

In this case, the posterior angulation was not encountered in the proximal trachea but rather in the more distal trachea. The extreme A-P tracheal deviation was not associated with any identifiable masses or lesions. A CT performed 2 months prior demonstrated normal tracheal anatomy, and there was no interval history of neck trauma or tracheal obstruction suggestive of a likely cause for this deviation. This change in the patient’s tracheal anatomy was only discovered after CPR had been performed and as part of the workup for cardiac arrest. Iatrogenic injuries are known to occur during CPR. Common CPR-related airway injuries include tracheal mucosal injury from traumatic intubation and bony injuries to the chest wall from compressions.11 Laryngeal cartilage damage from intubation may also occur, but tracheal displacement following CPR has not been previously reported.11

This case of tracheal deviation is unlikely to be related to patient positioning, as the A-P deviation persisted in 3 separate head and neck alignments. First, during indirect laryngoscopy, performed in a standard sniffing position. Second, during the CT, performed in the supine position, with no head support. The acute A-P deviation seen in Figure 2 was clearly noted in this position. Lastly, flexible fiber-optic bronchoscopy was performed in a semiupright position with the head supported on a pillow. A-P deviation was encountered and navigated in this position during flexible fiber-optic guided ETT repositioning. 

Using magnetic resonance imaging, alterations in the alignment of pharyngeal and tracheal axes have been described with changes in neck positioning; however, tracheal deviation has not been described with changes in head and neck alignment.12 Although the clinical presentation in this case was consistent with prior reports, we were unable to identify any previously reported anatomic cause for the tracheal deviation.5,6,8 Initial glottic visualization with a video laryngoscope was unremarkable, but resistance to sufficient ETT advancement past the vocal cords and a persistent air leak due to cuff herniation through the glottic opening was noticeable. The ETT was maneuvered to an appropriate position in the trachea using a flexible fiber-optic bronchoscope. The acute angulation of the trachea that was appreciated on bronchoscopy did not result in kinking of the ETT both initially and after in-situ thermosoftening of the polyvinyl chloride tube.13 Previously reported instances of A-P tracheal deviation have outlined the necessity of using alternative techniques to establish a patent airway, including the use of a laryngeal mask airway and a cuffless ETT with saline-soaked gauze packing.5,8 In 1 reported case, awake fiber-optic intubation was performed when difficult tracheal intubation was anticipated due to known A-P tracheal deviation.6

Failure of ETT advancement can be due to obstruction from the arytenoids and at the level of the vocal cords.14 When the ETT has been visualized to have traversed the vocal cords, tracheal A-P deviation should be considered as a cause of difficult ETT advancement. If an adequate endotracheal airway cannot be established, prompt consideration should be given to placement of a supraglottic airway. Early fiber-optic bronchoscopy should be used to establish the diagnosis and assist with proper ETT positioning.

Conclusions

This case illustrates the rare occurrence of A-P tracheal deviation leading to difficult intubation during CPR. The findings underscore the importance of considering A-P deviation as a potential cause of airway complications in emergency settings, especially in patients with previously normal tracheal anatomy. The successful use of flexible fiber-optic bronchoscopy in this case provides a valuable technique for addressing acute tracheal angulation. This report contributes to the limited literature on A-P tracheal deviation and serves as a reminder for clinicians to maintain a high index of suspicion for unusual airway challenges during critical interventions.

References
  1. Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797 

  2. Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8 

  3. Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100

  4. Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824

  5. Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386

  6. Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x

  7. De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2

  8. Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x

  9. Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6

  10. Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005

  11. Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9

  12. Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239

  13. Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06

  14. Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017

References
  1. Creasy JD, Chiles C, Routh WD, et al. Overview of traumatic injury of the thoracic aorta. Radiogr Rev Publ Radiol Soc N Am Inc. 1997;17:27-45. doi:10.1148/radiographics.17.1.9017797 

  2. Yee AM, Christensen DN, Waterbrook AL, et al. Parapharyngeal abscess with tracheal deviation. Intern Emerg Med. 2017;12:1077-1078.doi:10.1007/s11739-017-1634-8 

  3. Querney J, Singh SI, Sebbag I. Tracheal deviation with phrenic nerve palsy after brachial plexus block. Anaesth Rep. 2021;9:41-43. doi:10.1002/anr3.12100

  4. Geissler B, Wagner T, Dorn R, et al. Extensive sterile abscess in an invasive fibrous thyroiditis (Riedel’s thyroiditis) caused by an occlusive vasculitis. J Endocrinol Invest. 2001;24:111-115. doi:10.1007/BF03343824

  5. Kim HJ, Choi YS, Park SH, et al. Difficult endotracheal intubation secondary to tracheal deviation and stenosis in a patient with severe kyphoscoliosis: a case report. Korean J Anesthesiol. 2016;69:386-389. doi:10.4097/kjae.2016.69.4.386

  6. Crabb IJ. Anterior deviation of the trachea. Anaesthesia. 2001;56:284-286.doi:10.1046/j.1365-2044.2001.01918-17.x

  7. De Cassai A, Boscolo A, Rose K, et al. Predictive parameters of difficult intubation in thyroid surgery: a meta-analysis. Minerva Anestesiol. 2020;86:317-326. doi:10.23736/S0375-9393.19.14127-2

  8. Davies R. Difficult tracheal intubation secondary to a tracheal diverticulum and a 90 degree deviation in the trachea. Anaesthesia. 2000;55:923-925. doi:10.1046/j.1365-2044.2000.01664-18.x

  9. Cameron RB, Peacock WJ, Chang XG, et al. Double lumen endobronchial tube intubation: lessons learned from anatomy. BMC Anesthesiol. 2024;24:150. doi:10.1186/s12871-024-02517-6

  10. Walls RM, Samuels-Kalow M, Perkins A. A new maneuver for endotracheal tube insertion during difficult GlideScope intubation. J Emerg Med. 2010;39:86-88. doi:10.1016/j.jemermed.2009.11.005

  11. Buschmann CT, Tsokos M. Frequent and rare complications of resuscitation attempts. Intensive Care Med. 2009;35:397-404. doi:10.1007/s00134-008-1255-9

  12. Greenland KB, Edwards MJ, Hutton NJ, et al. Changes in airway configuration with different head and neck positions using magnetic resonance imaging of normal airways: a new concept with possible clinical applications. Br J Anaesth. 2010;105:683-690. doi:10.1093/bja/aeq239

  13. Takasugi Y, Futagawa K, Umeda T, et al. Thermophysical Properties of Thermosoftening Nasotracheal Tubes. Anesth Prog. 2018;65:100-105. doi:10.2344/anpr-65-02-06

  14. Phelan MP. Use of the endotracheal bougie introducer for difficult intubations. Am J Emerg Med. 2004;22:479-482. doi:10.1016/j.ajem.2004.07.017

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Physicians Face Medicare Telehealth Woes Amid Federal Government Shutdown

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Physicians Face Medicare Telehealth Woes Amid Federal Government Shutdown

The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

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The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

The ongoing US government partial shutdown has unintended consequences for seniors and their doctors as most telehealth appointments are now no longer being covered by Medicare.

That's because without a budget deal, federal lawmakers did not renew some pandemic-era telehealth flexibilities allowing Medicare beneficiaries to have medical appointments with doctors over audio or video at home.

This policy was first put into place under the first Trump Administration in 2020 during the COVID-19 pandemic. Previously, Medicare covered very limited telehealth services for rural patients.

For the past 5 years, lawmakers have always managed to renew the telehealth flexibilities in every government funding bill before the expiration date. This year, however, they expired for the first time on October 1.

Federal lawmakers remain at odds on the 2026 federal funding bill, meaning the shutdown could last into more days and even weeks.

But with Congress in a standoff, clinicians and patients outside Washington, DC, are already grappling with the consequences of the funding impasse.

Clinicians, Patients Already Feeling Effects

For the South Dakota-based Sanford Health System, which is the largest rural health system in the country, the past week without the Medicare telehealth waivers being in place has caused a lot of anxiety and uncertainty for both patients and clinicians.

Dave Newman, an endocrinologist and chief medical officer of virtual care at Sanford, said the health system decided to keep providing Medicare telehealth appointments to patients for now.

"We're maintaining telehealth access because we know that's the best thing for our patients. We've got full confidence that reimbursement will follow, but patients can't wait for Congress to act at this point," Newman told Medscape Medical News. "They still need access to their specialists. They still need access to their primary care providers, and this is one of the only ways that a lot of our patients get access. For them, it's either virtual care or no care at all."

Newman said as the shutdown continues, Sanford may reconsidered whether it can keep providing these appointments without reimbursement.

Some health systems have stopped providing an Medicare telehealth appointments, said Alexis Apple, director of federal affairs at the American Telemedicine Association. That means patients must appear in person for their doctor's appointment or cancel.

NYU Langone Health system's website currently has a banner that reads: "Due to the federal government shutdown, Medicare and Medicaid patients are unable to schedule new telehealth/video visits. If you already have a visit scheduled, it will continue as planned. If not, contact your doctor's office to schedule an in-person appointment.

"It's creating lots of confusion in the industry from patients, providers, hospital systems. You know, what do we do next? How do we grapple with this shutdown?" said Apple. "Patients have been able to receive care within their homes over the past 5 years, and now, all of a sudden, they've been stripped of that access."

Medicare patients who continue telehealth after October 1 may find out they're on the hook for the bill, if Congress doesn't act, said Apple.

Some physicians worry that commercial insurance payers may follow suit and no longer cover virtual appointments. Medicare, which is the largest health care payer in the country, is often seen as the standard for what services should be covered.

Patients and doctors have come to rely on telehealth as an integral part of health care, said Richard Chou, an anesthesiologist at the US Department of Veterans Affairs (VA) in Sacramento, California.

"You're seeing that postpandemic, telehealth is kind of a new way of doing things. It's part of the day for us as doctors," said Chou. He said tha tmany of his VA patients do their preliminary surgery appointments via telehealth before coming into the facility.

"Telehealth is that bridge to making sure patients get the care they need, and when these patients don't get that preliminary care they need, this builds up and builds up," said Chou. "And next thing you know, you have people flooding the emergency rooms, and we can't have that."

Will Telehealth Reimbursement See a Permanent Fix?

With Congressional budget negotiations at an impasse, it remains unclear when the shutdown will end.

Health care spending disagreements weigh heavily in negotiations. Democrats are currently unwilling to give the votes to pass the 60-vote threshold in the Senate unless Republicans agree to extend Affordable Care Act subsidies that expire at the end of the year. Democrats also want to reverse the Medicaid cuts that were part of the large Republican domestic tax and spending bill passed by Congress earlier this year.

When lawmakers do reach an agreement and reopen the government, it's likely telehealth flexibilities will be included in any package but for how long remains in question.

A newly introduced bipartisan bill would permanently allow Medicare patients to access telehealth appointments in their homes. But the legislation has been estimated to be very costly.

Federal data does show that telehealth appointments have been popular with Medicare recipients and increased over time since telehealth became more accessible.

"I used to say that virtual care was the future of medicine, and now it's just kind of the present of medicine. It used to be like a cool technology that we used to advertise, now it's just the standard of care," said Newman. "We think that permanent coverage would mean stability for both patients and providers."

Victoria Knight is a freelance reporter based in Washington, DC.

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

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Time to Reconsider Tramadol for Chronic Pain?

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Time to Reconsider Tramadol for Chronic Pain?

Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.

In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.

"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.

"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.

However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.

The study was published on October 7 in BMJ Evidence-Based Medicine.

Popularity Outpacing Proof

Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.

Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.

Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.

Small Benefit, Big Risk

The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.

"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.

The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.

Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.

Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.

The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.

Reevaluating Tramadol's Role

Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.

Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.

"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.

While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.

"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."

She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.

Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.

"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.

In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.

Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.

"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."

Written by Carla Cantor.

The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.

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

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Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.

In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.

"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.

"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.

However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.

The study was published on October 7 in BMJ Evidence-Based Medicine.

Popularity Outpacing Proof

Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.

Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.

Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.

Small Benefit, Big Risk

The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.

"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.

The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.

Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.

Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.

The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.

Reevaluating Tramadol's Role

Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.

Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.

"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.

While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.

"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."

She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.

Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.

"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.

In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.

Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.

"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."

Written by Carla Cantor.

The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.

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

Tramadol, a commonly prescribed opioid often viewed as a safer option for chronic pain, provided limited pain relief while increasing the risk for serious adverse effects, results of a new analysis showed.

In a systematic review and meta-analysis, investigators found that tramadol offered clinically insignificant pain relief, while doubling the likelihood of serious adverse events, most commonly cardiac complications.

"Given the limited analgesic benefits and increased risk of harm, tramadol use for chronic pain should be reconsidered," Jehad Ahmad Barakji, MD, of the Centre for Clinical Intervention Research at Rigshospitalet in Copenhagen, Denmark, told Medscape Medical News.

"Across different chronic pain conditions, tramadol's pain-relieving effect appears modest, and while some patients may experience relief, most will not gain substantial benefit," he added.

However, the researchers cautioned that the certainty of the evidence was low-to-moderate and that the quality of the underlying trials varied substantially.

The study was published on October 7 in BMJ Evidence-Based Medicine.

Popularity Outpacing Proof

Tramadol, a dual-action opioid that modulates serotonin and norepinephrine pathways, has long been promoted as a middle-ground analgesic - less addictive than morphine but stronger than nonopioid medications. It is approved for moderate-to-severe pain, including postoperative and chronic conditions.

Prescriptions have risen sharply worldwide, fueled by perceptions of safety and a belief that tramadol carries a lower risk for dependence. A recent global analysis estimated that nearly 18% of adults have used tramadol in their lifetime, and > 80% of those users combined it with at least 1 other substance.

Despite its widespread use, evidence supporting tramadol's long-term effectiveness and safety in chronic pain has been limited and inconsistent. Previous research has largely focused on short-term or condition-specific outcomes, such as osteoarthritis or neuropathic pain, leaving uncertainty about the drug's overall risk-benefit profile.

Small Benefit, Big Risk

The current study is the first comprehensive systematic review to evaluate tramadol alone for chronic pain using both meta-analysis and trail sequential analysis, provided a broader view of efficacy and safety across pain types.

"We sought to fill this gap by evaluating the totality of evidence to guide clinical practice," Barakji said.

The analysis included 19 randomized, placebo-controlled trials with 6569 adults. The average participant age was 56 years, and study durations ranged from 4 to 16 weeks. Pain intensity was typically assessed with the 0-10 numeric rating scale (NRS), while function and quality of life were measured with validated patient-reported tools.

Across the pooled analysis, participants receiving tramadol experienced an average pain reduction of 0.9 points on the NRS compared with placebo - a difference below the 1-point threshold considered clinically meaningful. About 7% more patients in the tramadol groups achieved noticeable pain relief, but investigators said the benefit was modest and uncertain.

Serious adverse events were twice as common among tramadol users, most often involving cardiac complications such as chest pain, coronary artery disease, or heart failure. Nonserious adverse effects, including nausea, dizziness, constipation, and drowsiness, were frequent and contributed to higher discontinuation rates among tramadol recipients.

The researchers acknowledged that most included trials were at a high risk for bias due to incomplete outcome reporting, small sample sizes, and inconsistent assessment methods, factors that may have exaggerated benefits and underestimated harms.

Reevaluating Tramadol's Role

Commenting on the research, Jessica Otte, MD, clinical associate professor in the Department of Family Medicine at The University of British Columbia, Vancouver, British Columbia, Canada, said the new review stands out for examining tramadol's use across a range of chronic pain conditions, an area where clinicians often struggle to help patients achieve meaningful and sustained relief.

Otte, who has studied the drug's safety and effectiveness through The University of British Columbia's Therapeutics Initiative, said the Danish team's analysis expands on earlier research that largely focused on single pain conditions. The findings, she said, add weight to growing evidence that challenges tramadol's perceived advantages over other analgesics.

"This review doesn't change the narrative but strengthens it: Tramdol's reputation as a safer or uniquely effective opioid is increasingly difficult to defend," she told Medscape Medical News.

While she believes the study makes an important contribution, Otte said the results should be interpreted with caution because of gaps in the underlying evidence. The Danish authors noted similar concerns, and Otte agreed that many of the included trials had methodological shortcomings.

"A lot of the studies had biases that made use less certain about what was reported," she said. "Many outcomes that matter to patients - like quality of life, functional improvement, or withdrawal - were either inconsistently measured or not reported at all."

She added that patients assigned to tramadol were more likely to discontinue early, both overall and because of adverse effects, raising concern about tolerability and attrition bias.

Also commenting, Houman Danesh, MD, professor and medical director of pain management at the Icahn School of Medicine at Mount Sinai in New York City, said the review provides moderate-certainty evidence that tramadol increases the risk for serious adverse events; but its broad approach - evaluating efficacy and safety across multiple chronic pain conditions - could be a confounding factor.

"Tramadol may benefit some conditions more than others," he noted, which could alter the overall risk-benefit profile.

In his clinical experience, Danesh said severe complications such as cardiac events are uncommon. He explained that heart rhythm disturbances occasionally associated with tramadol generally arise when patients are taking other medications that affect cardiac conduction.

Danesh emphasized that clinicians should weigh the study alongside other research and their own experience when deciding whether to prescribe the drug.

"It's important to take this study into consideration," he said, "but there are multiple studies that support the use of tramadol, and we have to look at the totality of the evidence."

Written by Carla Cantor.

The authors declared no competing interests and received no specific grant from any funding agency. Otte and Danesh reported no relevant financial relationships.

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

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mRNA Cancer Vaccines: Pipeline Insights for Clinicians

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Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

  • Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
  • Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
  • Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

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Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

  • Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
  • Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
  • Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.

In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.

Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.

Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.

“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”

Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”

 

Challenges With mRNA Vaccines

Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.

Global Research Status

According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.

Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.

Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.

 

Leading Studies

Lepique highlighted the most advanced studies to date:

  • Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
  • Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
  • Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.

Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.

Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.

 

Advantages of mRNA Technology

Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.

“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.

It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.

Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.

 

Outlook and Limitations

Lima noted that although the projected efficacy is promising, definitive results are still pending.

“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.

According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.

“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.

Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.

Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”

This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.

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US Health Official Calls for Separating Measles Combination Shots, Pulls Broad COVID Vaccine Support

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(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.

The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.

The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.

In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.

Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.

The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.

 

MERCK, EXPERTS DEFEND MMR SHOT

Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot. 

According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.

“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.

Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.

“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”

GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.

The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security. 

“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.

Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.

Merck also makes the measles-mumps-rubella-varicella shot.

CDC CHANGES COVID VIEWS      

The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.

The immunization schedules will be updated on the CDC website by Tuesday, the agency said.

The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence. 

The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.

The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.

The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.

The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.

(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)

A version of this article appeared on Medscape.com.

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(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.

The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.

The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.

In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.

Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.

The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.

 

MERCK, EXPERTS DEFEND MMR SHOT

Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot. 

According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.

“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.

Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.

“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”

GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.

The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security. 

“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.

Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.

Merck also makes the measles-mumps-rubella-varicella shot.

CDC CHANGES COVID VIEWS      

The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.

The immunization schedules will be updated on the CDC website by Tuesday, the agency said.

The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence. 

The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.

The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.

The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.

The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.

(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)

A version of this article appeared on Medscape.com.

(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.

The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.

The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.

In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.

Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.

The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.

 

MERCK, EXPERTS DEFEND MMR SHOT

Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot. 

According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.

“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.

Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.

“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”

GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.

The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security. 

“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.

Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.

Merck also makes the measles-mumps-rubella-varicella shot.

CDC CHANGES COVID VIEWS      

The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.

The immunization schedules will be updated on the CDC website by Tuesday, the agency said.

The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence. 

The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.

The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.

The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.

The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.

(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)

A version of this article appeared on Medscape.com.

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Hepatitis D Virus Classified as Carcinogenic: Implications

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The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

  • Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
  • Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

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The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

  • Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
  • Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).

Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.

About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.

 

Virus Biology

HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.

HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.

 

Cancer Risk

HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.

The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.

Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.

 

Treatment Options

Randomized controlled trials have demonstrated antiviral efficacy for:

  • Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
  • Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.

Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.

Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.

 

Guideline Updates

The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.

IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.

 

HBV Vaccination

HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.

Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.

Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.

Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.

STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.

Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.

This story was translated from Univadis Germany.

A version of this article appeared on Medscape.com.

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