People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Healthcare costs for patients undergoing common surgical procedures are significantly higher when the surgery is performed by a male surgeon rather than a female surgeon, data suggested.

A retrospective, population-based cohort study that included more than 1 million adults undergoing any of 25 common surgical procedures found that total healthcare costs assessed at 1 year following surgery were more than $6000 higher when the surgery was performed by a male surgeon. Costs were also higher at 30 and 90 days for patients treated by male surgeons.

“As a male surgeon, I think our results should cause me and my colleagues to pause and consider why this may be,” said lead author Christopher J. D. Wallis, MD, PhD, assistant professor of surgery at the University of Toronto.

“None of us believe that the presence of a Y chromosome in surgeons means there are worse outcomes, it’s just that generally speaking, men and women, as we have known for decades, practice medicine a little differently. Things like communication style, time they spend with their patients, and even things like guideline adherence are different, and understanding how those differences translate into patient outcomes is the goal of this whole body of work,” said Wallis.

The study was published online November 29 in JAMA Surgery.

Explanation Is Elusive

In earlier work, Dr. Wallis and his team reported that patients treated by female surgeons had a small but statistically significant decrease in 30-day mortality, were less likely to be readmitted to the hospital, and had fewer complications than those treated by male surgeons. In another study, they found worse outcomes among female patients treated by male surgeons.

In the current study, the researchers examined the association between surgeon sex and healthcare costs among patients undergoing various surgical procedures, including coronary artery bypass grafting, appendectomy, hysterectomy, anterior spinal decompression, and knee replacement. They included all adult patients who underwent these procedures at hospitals in Ontario, Canada, between January 2007 and December 2019 in their analysis.

The study sample included 1,165,711 patients. Of this group, 151,054 patients were treated by a female surgeon, and 1,014,657 were treated by a male surgeon.

After adjusting for patient-, surgeon-, anesthesiologist-, and hospital-related factors, they found that 1-year total healthcare costs were $24,882 for patients treated by male surgeons vs $18,517 for patients treated by female surgeons. Healthcare costs were also higher at 30 days (adjusted absolute difference, $3115) and at 90 days (adjusted absolute difference, $4228).

“This translates into a 9%-10% higher risk of costs with male surgeons compared with women surgeons at these time points,” said Dr. Wallis.

“This study cannot provide a specific answer as to why these differences are occurring,” Dr. Wallis said.

“We are currently undertaking more research to better understand the reasons. Our previous studies have shown that patients treated by male physicians have higher rates of death, readmission, and complications. Managing these adverse postoperative events is costly and likely contributes to these differences. Given the size of our study and similar training pathways, we do not think there are technical differences between male and female surgeons. Rather, we are hypothesizing that there may be differences in how physicians practice, make decisions, and consult with patients,” he said.

Ultimately, Dr. Wallis said he would like his research to prompt “a moment of introspection” among his surgical colleagues.

“Hopefully, these data will provide the impetus for further efforts to make surgery, and medicine in general, a field that is welcoming to women,” he said.

Potential Confounding Factors

This study expands the evidence suggesting significant practice differences between male and female surgeons, Ursula Adams, MD, a resident; Caprice C. Greenberg, MD, MPH, chair; and Jared Gallaher, MD, MPH, adjunct assistant professor, all from the Department of Surgery at the University of North Carolina in Chapel Hill, wrote in an accompanying editorial.

They cautioned, however, that “there are many potential confounding factors and possible explanatory mechanisms associated with surgeon sex that make it challenging to untangle influences on costs. Sex may be an easily captured data point, but is understanding the mechanism by which it affects cost the right next step? Surgeons control how and where they practice; they do not have control over their own demographics.”

The editorialists added that while recruiting and retaining women in surgery is important, it is not a solution to controlling costs.

“We must provide surgeons with better data to understand how practice approach and decisions affect cost and support for practice improvement. Only with these insights will we ensure patients of male surgeons receive care that is just as cost-effective as that provided by female surgeons, while also helping to bend the cost curve and improve the quality of surgical care,” they concluded.

‘Admirable’ Data Use

Commenting on the findings, Oluwadamilola “Lola” Fayanju, MD, chief of breast surgery at Penn Medicine in Philadelphia, said, “It is interesting that the study was performed in Canada with its different healthcare system.” Dr. Fayanju did not participate in the study.

“They used administrative data from a national database, and it is admirable that they were able to do that. These data allow us to make large-scale geographical assessments, although they are subject to errors and unmeasured confounders,” said Dr. Fayanju.

Women surgeons may do things that result in better outcomes, she suggested. “In this study, the women were younger and so perhaps were more up to date. They might have optimized management of their patients in the pre-op phase, including better patient selection, which led to better costs. Or in the post-op phase, they might have made themselves readily accessible. For instance, I remove all barriers about getting in touch with me, and I tell my students to make sure the patient can reach you easily,” said Dr. Fayanju.

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care, and the Data Sciences Institute at the University of Toronto. Dr. Wallis, Dr. Adams, Dr. Greenberg, Dr. Gallaher, and Dr. Fayanju reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.

METHODOLOGY:

• Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
• Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
• For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
• Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.

TAKEAWAY:

• Individuals with hypochondriasis had an 84% higher risk for all-cause mortality during the study period than those without it (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
• The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
• The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
• When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.

IN PRACTICE:

“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.

SOURCE:

David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.

LIMITATIONS:

Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.

DISCLOSURES:

The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.

A version of this article appeared on Medscape.com.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Maintaining remission in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis who have kept their autoantibodies in check after at least 2 years on rituximab therapy has proved challenging, but a team of nephrologists in Boston have reported that a longer-term strategy that uses a rise in B-cell levels as a threshold for rituximab infusions may be the better of two strategies at reducing relapse risks. 

“The bottom line is with the B-cell strategy, which is that rituximab was redosed when the B cells recovered or started to recover, we only have a 6% rate in relapses by 3 years,” senior study author John L. Niles, MD, assistant professor of medicine at the Harvard Medical School and director of the Vasculitis and Glomerulonephritis Center at Massachusetts General Hospital in Boston, Massachusetts, told Medscape Medical News.

Massachusetts General Hospital

“Whereas in the other strategy, we were waiting for a serologic relapse and hoping we could prevent clinical relapses, but we still have about 30% rate of relapse by 3 years.”

Dr. Niles and his associates reported their findings from the MAINTANCVAS study (for MAINTenance of ANCA VASculitis) December 11, 2023, in Annals of the Rheumatic Diseases. Their single-center study compared two different treatment strategies in patients with ANCA-associated vasculitis in remission after completing at least 2 years of fixed-schedule rituximab therapy: an approach that reinfused rituximab upon B-cell repopulation, called the B-cell arm and a strategy that reinfused rituximab when serologic levels of ANCA increased significantly, which they called the ANCA arm. A total of 115 patients were randomly assigned to either arm.
 

Study Results

Median follow-up was 4.1 years from study entry. Throughout the study, 5 of 58 patients in the B-cell arm and 14 of 57 in the ANCA arm had relapses. According to Kaplan-Meier analysis, at 3 years after study entry, 4.1% of patients in the B-cell arm had a relapse vs 20.5% of patients in the ANCA arm. At 5 years, the respective relapse rates were 11.3% and 27.7%. Overall, four major relapses occurred in the B-cell arm and seven in the ANCA arm.

The COVID-19 pandemic caused the researchers to halt the study before it was fully enrolled, Dr. Niles said. The study also attributed high rates of serious adverse events (SAEs) in the B-cell arm to cases of COVID-19 in that study population. The overall number of SAEs was identical in both arms: 22 (P = .95). But the B-cell arm had six cases of COVID-19 vs one in the ANCA arm, including two deaths because of COVID-19.

The study findings provided insight into how to best individualize treatment in patients with ANCA-associated vasculitis, Dr. Niles said. “We will typically start with the B-cell strategy after 2 years, but to the extent that people have infections or hypogammaglobulinemia, we’ll start stretching a little longer on the B cells, and if the level is too high in terms of infection, we’ll stop and switch to the ANCA strategy,” he said.

He added, “Relapsers get a more strict B-cell strategy, and people with infections get much longer intervals or even switch entirely to the ANCA strategy.”

Because the study ended before it was fully enrolled, it was underpowered for subgroup analyses, Dr. Niles noted. One such potential subgroup was relapsing patients with interstitial lung disease as the primary clinical finding. “The interstitial lung disease doesn’t seem to respond as well to therapy as the other classic features of ANCA disease,” Dr. Niles said. “It’s the one part that’s the most problematic for the long run. It behaves differently, and there’s going to need to be more research on ILD. Fortunately, it’s a fairly small percentage of the total group, but it’s the most difficult part of this disease.”
 

Findings in Context

This study brings clarity on how to best manage patients with ANCA-associated vasculitis, Robert Hylland, MD, an assistant clinical professor of rheumatology at Michigan State University College of Osteopathic Medicine, told this news organization.

“Most of us have tried to discern from the literature that exists how to manage [ANCA-associated vasculitis]. There have been a number of different approaches, and they have changed over the course of time,” Dr. Hylland said. “But now this article helps us to understand how to proceed with this disease after we have induced remission. The ability to determine the validity of serology vs B-cell depletion was brought out very nicely in this article.”

Michigan State University College of Osteopathic Medicine

The size of the study population was a strength of the study, Dr. Hylland said. 

He credited the study authors for providing insight into using positive myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA readings to guide treatment for relapses. The study defined a serologic ANCA flare in the ANCA arm as a fivefold increase in MPO and a fourfold rise in PR3.

“Many of us wouldn’t have recognized that a less than fivefold increase, for example, in the MPO could be watched for a while, where most of us would have been treating that serologic flare,” Hylland said.

The study also highlighted the difficulty of evaluating a patient who has neither a positive ANCA nor a significant increase in their B-cell counts and yet still has clinical signs and symptoms of a relapse, such as with granulomatosis with polyangiitis, also known as Wegener’s granulomatosis.

“A lot of physicians tend to feel a little more relaxed when they see their patient is serologically doing well and yet, when they come in, some of the subtle symptoms of Wegener’s could be ignored if you don’t recognize that there’s a considerable number who will come to you with having had treatment and still have negative serology,” Hylland said.

The study had no specific outside funding source. Dr. Niles and Dr. Hylland report no relevant financial relationships. Two co-authors report financial relationships with pharmaceutical companies.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

Neuroinflammation expert Jarred Younger, PhD, disputes a recent study commentary calling for clinicians to stop prescribing low-dose naltrexone for people with fibromyalgia.

Naltrexone is a nonselective µ-opioid receptor antagonist approved by the US Food and Drug Administration (FDA) at doses of 50-100 mg/day to treat opioid and alcohol dependence. Lower doses, typically 1-5 mg, can produce an analgesic effect via antagonism of receptors on microglial cells that lead to neuroinflammation. The low-dose version, available at compounding pharmacies, is not FDA-approved, but for many years it has been used off-label to treat fibromyalgia and related conditions.

Results from earlier small clinical trials have conflicted, but two conducted by Dr. Younger using doses of 4.5 mg/day showed benefit in reducing pain and other fibromyalgia symptoms. However, a new study from Denmark on 6 mg low-dose naltrexone versus placebo among 99 women with fibromyalgia demonstrated no significant difference in the primary outcome of change in pain intensity from baseline to 12 weeks.

On the other hand, there was a significant improvement in memory, and there were no differences in adverse events or safety, the authors reported in The Lancet Rheumatology.

Nonetheless, an accompanying commentary called the study a “resoundingly negative trial” and advised that while off-label use of low-dose naltrexone could continue for patients already taking it, clinicians should not initiate it for patients who have not previously used it, pending additional data.

Dr. Younger, director of the Neuroinflammation, Pain and Fatigue Laboratory at the University of Alabama, Birmingham, was speaking on December 13, 2023, at a National Institutes of Health meeting about myalgic encephalomyelitis/chronic fatigue syndrome about the potential use of low-dose naltrexone for that patient population. He had checked the literature in preparation for his talk and saw the new study, which had just been published December 5, 2023. 

During his talk, Dr. Younger said, “It looks like the study was very well done, and all the decisions made sense to me, so I don’t doubt the quality of their data or the statistics.”

But as for the commentary, he said, “I strongly disagree, and I believe the physicians at this conference strongly disagree with that as well. I know plenty of physicians who would say that is not good advice because this drug is so helpful for so many people.”

Indeed, Anthony L. Komaroff, MD, who heard Dr. Younger’s talk but hadn’t seen the new study, told this news organization that he is a “fan” of low-dose naltrexone based on his own experience with one patient who had a “clearly beneficial response” and that of other clinicians he’s spoken with about it. “My colleagues say it doesn’t work for everyone because the disease is so heterogeneous ... but it definitely works for some patients.”

Dr. Younger noted that the proportion of people in the Danish study who reported a clinically significant, that is 30% reduction, in pain scores was 45% versus 28% with placebo, not far from the 50% he found in his studies. “If they’d had 40 to 60 more people, they would have had statistically significant difference,” Dr. Younger said.

Indeed, the authors themselves pointed this out in their discussion, noting, “Our study was not powered to detect a significant difference regarding responder indices ... Subgroups of patients with fibromyalgia might respond differently to low-dose naltrexone treatment, and we intend to conduct a responder analysis based on levels of inflammatory biomarkers and specific biomarkers of glial activation, hypothesising that an inflammatory subgroup might benefit from the treatment. Results will be published in subsequent papers.”

The commentary authors responded to that, saying that they “appreciate” the intention to conduct that subgroup analysis, but that it is “probable that the current sample size will preclude robust statistical comparisons but could be a step to generate hypotheses.”

Those authors noted that a systematic review has described both pro-inflammatory (tumor necrosis factor, interleukin [IL]-6, and IL-8) and anti-inflammatory (IL-10) cytokines as peripheral inflammatory biomarkers in patients with fibromyalgia. “The specific peripheral biomarkers of glial activation are yet to be identified. The neuroinflammation hypothesis of fibromyalgia could be supported if a reduction of central nervous system inflammation would predict improvement of fibromyalgia symptoms. Subsequent work in this area is eagerly awaited.”

In the meantime, Dr. Younger said, “I do not think this should stop us from looking at low-dose naltrexone [or that] we shouldn’t try it. I’ve talked to over a thousand people over the last 10 years. It would be a very bad thing to give up on low-dose naltrexone now.”

Dr. Younger’s work is funded by the National Institutes of Health, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Komaroff has no disclosures.

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Happy New Year, everyone. It’s hard to believe, but we are nearing the mid-point of our five-year term on the GI & Hepatology News (GIHN) board of editors. Our central goal over the past two-and-a-half years has been to curate thought-provoking content for GIHN that helps to inform clinical practice and keeps you up-to-date on emerging scientific innovations and policy changes impacting patients with digestive and liver diseases.

As we usher in 2024, we want to hear from you—our readers—to ensure we are appropriately tailoring our coverage to your needs. Your feedback is critical to ensuring the continued success of the newspaper as your go-to source for cutting edge news relevant to our field.

To start, we welcome your thoughts on the following questions:

• What do you want to see more of in the newspaper (e.g., a particular column, topic)?
• How can we continue to serve you best as a reader? 

Please email your feedback to us at [email protected]. Your input is greatly appreciated by both the board and our larger editorial team and will help inform future coverage.

In this month’s issue of GIHN, we update you on the proceedings of AGA’s 2023 Innovation Conference, highlight a new Clinical Practice Guideline focused on the role of biomarkers in Crohn’s disease management, and summarize key AGA journal content.

The AGA Government Affairs Committee also details 2024 updates to Medicare payment rules, including a new add-on code for complex care, increased facility payment for POEM procedures, and continuation of expanded telehealth coverage through the end of 2024.

GIHN associate editor Dr. Avi Ketwaroo introduces this month’s Perspectives column focused on the impact of substance use (specifically alcohol and marijuana) on liver transplant candidacy.

In our January Member Spotlight, we feature Dr. Sonali Paul, a hepatologist and co-founder of Rainbows in Gastro. She shares her passion for promoting health equity in sexual and gender minority populations.

We hope you enjoy this, and all the exciting content included in our January issue.

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Happy New Year, everyone. It’s hard to believe, but we are nearing the mid-point of our five-year term on the GI & Hepatology News (GIHN) board of editors. Our central goal over the past two-and-a-half years has been to curate thought-provoking content for GIHN that helps to inform clinical practice and keeps you up-to-date on emerging scientific innovations and policy changes impacting patients with digestive and liver diseases.

As we usher in 2024, we want to hear from you—our readers—to ensure we are appropriately tailoring our coverage to your needs. Your feedback is critical to ensuring the continued success of the newspaper as your go-to source for cutting edge news relevant to our field.

To start, we welcome your thoughts on the following questions:

• What do you want to see more of in the newspaper (e.g., a particular column, topic)?
• How can we continue to serve you best as a reader? 

Please email your feedback to us at [email protected]. Your input is greatly appreciated by both the board and our larger editorial team and will help inform future coverage.

In this month’s issue of GIHN, we update you on the proceedings of AGA’s 2023 Innovation Conference, highlight a new Clinical Practice Guideline focused on the role of biomarkers in Crohn’s disease management, and summarize key AGA journal content.

The AGA Government Affairs Committee also details 2024 updates to Medicare payment rules, including a new add-on code for complex care, increased facility payment for POEM procedures, and continuation of expanded telehealth coverage through the end of 2024.

GIHN associate editor Dr. Avi Ketwaroo introduces this month’s Perspectives column focused on the impact of substance use (specifically alcohol and marijuana) on liver transplant candidacy.

In our January Member Spotlight, we feature Dr. Sonali Paul, a hepatologist and co-founder of Rainbows in Gastro. She shares her passion for promoting health equity in sexual and gender minority populations.

We hope you enjoy this, and all the exciting content included in our January issue.

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Happy New Year, everyone. It’s hard to believe, but we are nearing the mid-point of our five-year term on the GI & Hepatology News (GIHN) board of editors. Our central goal over the past two-and-a-half years has been to curate thought-provoking content for GIHN that helps to inform clinical practice and keeps you up-to-date on emerging scientific innovations and policy changes impacting patients with digestive and liver diseases.

As we usher in 2024, we want to hear from you—our readers—to ensure we are appropriately tailoring our coverage to your needs. Your feedback is critical to ensuring the continued success of the newspaper as your go-to source for cutting edge news relevant to our field.

To start, we welcome your thoughts on the following questions:

• What do you want to see more of in the newspaper (e.g., a particular column, topic)?
• How can we continue to serve you best as a reader? 

Please email your feedback to us at [email protected]. Your input is greatly appreciated by both the board and our larger editorial team and will help inform future coverage.

In this month’s issue of GIHN, we update you on the proceedings of AGA’s 2023 Innovation Conference, highlight a new Clinical Practice Guideline focused on the role of biomarkers in Crohn’s disease management, and summarize key AGA journal content.

The AGA Government Affairs Committee also details 2024 updates to Medicare payment rules, including a new add-on code for complex care, increased facility payment for POEM procedures, and continuation of expanded telehealth coverage through the end of 2024.

GIHN associate editor Dr. Avi Ketwaroo introduces this month’s Perspectives column focused on the impact of substance use (specifically alcohol and marijuana) on liver transplant candidacy.

In our January Member Spotlight, we feature Dr. Sonali Paul, a hepatologist and co-founder of Rainbows in Gastro. She shares her passion for promoting health equity in sexual and gender minority populations.

We hope you enjoy this, and all the exciting content included in our January issue.

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.

Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.

University of Chicago

“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.

In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.

Dr. Paul has worked to establish policies such as documenting preferred gender identity of patients in electronic medical records and using pronoun cards on ID badges to make LGBTQI+ patients more comfortable. Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.

In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.

Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?

Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.

Q: What are your hopes and aspirations for the field of GI moving forward?

Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.

For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?

Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?

Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.

I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.

Q: What do you think about the new weight loss drugs?

Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.

Q: Is there any type of research you’re doing in this area right now?

Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.

LIGHTNING ROUND

What is your favorite junk food? 
Doritos

What is your favorite holiday?
Thanksgiving

Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri 

What is your favorite movie genre?
Comedy

Are you an introvert or extrovert? 
Somewhere in the middle.

Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.

Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.

University of Chicago

“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.

In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.

Dr. Paul has worked to establish policies such as documenting preferred gender identity of patients in electronic medical records and using pronoun cards on ID badges to make LGBTQI+ patients more comfortable. Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.

In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.

Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?

Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.

Q: What are your hopes and aspirations for the field of GI moving forward?

Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.

For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?

Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?

Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.

I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.

Q: What do you think about the new weight loss drugs?

Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.

Q: Is there any type of research you’re doing in this area right now?

Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.

LIGHTNING ROUND

What is your favorite junk food? 
Doritos

What is your favorite holiday?
Thanksgiving

Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri 

What is your favorite movie genre?
Comedy

Are you an introvert or extrovert? 
Somewhere in the middle.

Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.

Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.

University of Chicago

“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.

In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.

Dr. Paul has worked to establish policies such as documenting preferred gender identity of patients in electronic medical records and using pronoun cards on ID badges to make LGBTQI+ patients more comfortable. Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.

In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.

Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?

Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.

Q: What are your hopes and aspirations for the field of GI moving forward?

Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.

For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?

Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?

Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.

I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.

Q: What do you think about the new weight loss drugs?

Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.

Q: Is there any type of research you’re doing in this area right now?

Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.

Q: Describe how you would spend a free Saturday afternoon.

Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.

LIGHTNING ROUND

What is your favorite junk food? 
Doritos

What is your favorite holiday?
Thanksgiving

Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri 

What is your favorite movie genre?
Comedy

Are you an introvert or extrovert? 
Somewhere in the middle.