Feature

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Katie Sullivan, DNP, FNP-C, is publicizing her own challenge with updating an insulin pump as part of an effort to bring an end to the biannual seasonal clock changes in the United States.

On March 10, 2024, Sullivan, who works in the Endocrinology Clinic, Michigan State University, East Lansing, Michigan, mistakenly reversed the AM and PM settings while adjusting her own insulin pump. Sullivan, who has type 1 diabetes, noticed several hours later that her blood glucose levels had become higher than usual and was surprised to see her pump showed sleep mode during the day.

She was able to address this glitch before going to sleep and thus “escaped a potential occurrence of nocturnal hypoglycemia,” Sullivan and her colleague, Saleh Aldasouqi, MD, wrote in a September commentary in the journal Clinical Diabetes.

The risk of daylight saving time (DST) changes for people with insulin pumps is well known. Aldasouqi himself raised it in a 2014 article in the Journal of Diabetes Science and Technology.

Medtronic Inc., the leading maker of insulin pumps, told this news organization in an email that it intends for future devices to automate DST changes. The company did not provide any further details on when such changes would happen.

For now, Medtronic and other makers of insulin pumps join in twice-a-year efforts to remind people they need to update their devices to adjust for DST changes. They will need to gear up these outreach campaigns, which include social media posts, again ahead of the end of DST on November 3, when clocks shift back an hour. Diabetes clinics and hospitals also send notes to patients.

Even so, people will fail to make this change or to do it correctly.

“Despite our efforts to educate our patients about DST glitches, we have detected incorrect time settings in some of our patients’ insulin pumps after the DST changes in the fall and spring and occasional cases of incorrect insulin dosing, resulting in hyperglycemia or hypoglycemia,” Sullivan and Aldasouqi wrote in their article.

The US Food and Drug Administration (FDA) database of injuries and mishaps with devices contains many reports about patients not adjusting their insulin pumps for DST.

Known as Manufacturer and User Facility Device Experience (MAUDE), this database does not provide identifying details about the patients. Instead, the reports contain only a few lines describing what happened. In many cases, people were able to easily resolve their temporary glycemic issues and then set their devices to the correct time.

But some of the MAUDE reports tell of more severe consequences, with people ending up in emergency rooms because they did not adjust their insulin pumps for DST.

Among these is a report about a November 2022 incident, where a patient suffered due to what appeared to be inaccurate continuous glucose monitor readings, combined with the effects of an insulin pump that had not been updated for a DST change.

Although that patient’s mother was available to assist and the patient consumed three dextrose candies, the patient still reportedly lost consciousness and experienced tremors. That led to hospitalization, where the patient was treated with intravenous saline, intravenous insulin, saline fluids, and insulin fluids. The patient left the hospital with “the issue resolved and no permanent damage” but then switched to another method of insulin therapy, the MAUDE report said.

It’s unclear how often DST changes lead to problems with insulin pumps, reflecting difficulties in tracking flaws and glitches in medical devices, Madris Kinard, the chief executive officer and founder of Device Events, told this news organization.

The FDA relies heavily on passive surveillance, gathering MAUDE reports submitted by companies, clinicians, and patients. That means many cases likely are missed, said Kinard who earlier worked as an analyst at the FDA, updating processes and systems to help identify risky devices.

For example, Sullivan told this news organization she had not filed a report for her incident with the insulin pump.
 

Permanent Standard Time?

Many clinicians, including Aldasouqi and Sullivan, argue a better solution to these challenges would be to end DST.

In their Clinical Diabetes article, they also cited other health risks associated with clock changes such as fatigue, headache, and loss of attention and alertness that can result in injuries.

But a permanent time change is a “politically charged issue, and it continues to be debated nationally and at the state level,” they wrote.

At least 30 states also considered measures this year related to DST, according to the National Conference of State Legislatures. A pending Senate bill intended to make DST permanent has the support of 8 Democrats and 11 Republicans, including Sen. Tommy Tuberville (R-Ala).

“It’s amazing how many phone calls we get over this one topic. People across America agree that changing our clocks back and forth twice a year really makes no sense,” Tuberville said last year on the Senate floor. “People call and say they’re just sick of it.”

These federal and state efforts have stalled to date on the key question of whether to make either standard time or DST permanent, the National Conference of State Legislatures noted. A shift to permanent DST might have benefits for some agricultural and recreational industries, but many physicians say it would be bad for people’s health.

The American Academy of Sleep Medicine (AASM) argues strongly for moving to permanent standard time. In a position statement published in the Journal of Clinical Sleep Medicine, the group said the acute transitions from standard time to DST pose harms, citing research indicating increased risks for adverse cardiovascular events, mood disorders, and motor vehicle crashes.

The solution is to end shifts in time and opt for standard time, which best aligns with the human biological clock, AASM said.

AASM noted that there already was a failed experiment in the United States with a shift to permanent DST. Congress established this in response to the 1973 OPEC oil embargo, expecting that allowing more evening hours with light would lead to energy savings. That didn’t pay off in the expected reduction in energy and the policy was highly unpopular, especially in rural areas, AASM said.

“After a single winter, the policy was reversed by an overwhelming congressional majority,” wrote Muhammad Adeel Rishi, MD, and other authors of the statement. “The unpopularity of the act was likely because despite greater evening light, the policy resulted in a greater proportion of days that required waking up on dark mornings, particularly in the winter.”

Karin G. Johnson, MD, professor of neurology at the UMass Chan School of Medicine, Worcester, Massachusetts, told this news organization that a shift to permanent DST would rob many people of the signals their bodies need for sleep.

“Sunrises and sunsets are later and that creates a desire for our body to stay up later and have more trouble getting up in the morning,” Johnson said. “You’re all but making it impossible for certain segments of the population to get enough sleep” with permanent DST.

Johnson, Sullivan, and Aldasouqi had no relevant financial disclosures.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Researchers may be on track to develop a much-needed tool for studying endometriosis: A noninvasive stool test that could replace the current gold standard of laparoscopy.

Their approach, which focuses on the link between the gut microbiome and endometriosis, also identified a bacterial metabolite they said might be developed as an oral medication for the condition, which affects at least 11% of women.

In previous research, Rama Kommagani, PhD, an associate professor in the Department of Pathology & Immunology at Baylor College of Medicine in Houston, Texas, worked with a mouse model in which endometrial tissue from donor rodents was injected into the peritoneal space of healthy rodents to induce the disorder.

Transfer of fecal microbiota from mice with endometriosis to those without the condition induced the trademark lesions, suggesting the microbiome influences the development of endometriosis. Treating the animals with the antibiotic metronidazole inhibited the progression of endometrial lesions.

Kommagani speculated the microbes release metabolites that stimulate the growth of the endometrial lesions. “Bad bacteria release metabolites, you know, which actually promote the disease,” Kommagani said. “But the good bacteria might release some protective metabolites such as short-chain fatty acids.”

In a new study, Kommagani and his colleagues sought to identify a unique profile of bacteria-derived metabolites that could reliably diagnose endometriosis. Using stool specimens from 18 women with the condition and 31 without the disease, his team conducted whole metabolic profiling of the gut microbiota.

After identifying hundreds of metabolites in the samples, further analysis revealed a subset of 12 metabolites that consistently differentiated women with and without endometriosis.

These findings led to more questions. “If a metabolite is lower in women with endometriosis, does it have any functional relevance?” Kommagani said.

One candidate was 4-hydroxyindole (4HI), which was found in lower levels in the stool of patients. This substance is a little-understood derivative of its parent compound, indole, which occurs naturally in plants and has a wide range of therapeutic uses.

Using a mouse model, Kommagani’s lab demonstrated that feeding mice 4HI before receiving an endometrial transplant prevented the development of lesions typical of endometriosis. Mice given 4HI after they had developed endometriosis showed regression of lesions and decreased response to painful stimuli.

“In a nutshell, we found a specific set of bacterial metabolites in stool, which could be used towards a noninvasive diagnostic test,” Kommagani said. “But we also found this distinct, specific metabolite that could be used as a therapeutic molecule.” 

Tatnai Burnett, MD, an assistant professor of obstetrics and gynecology at Mayo Clinic in Rochester, Minnesota, who is not associated with the study, said a noninvasive test would have several advantages over the current methods of diagnosing endometriosis. Clinicians could detect and treat women earlier in the course of their disease. Secondly, a test with sufficient negative predictive value would be helpful in deciding whether to initiate treatment with hormones or other oral medications or go straight to surgery. “I would choose not to do a surgery if I knew with enough certainty that I wasn’t going to find anything,” said Burnett.

Lastly, a test that was quantitative and showed a response to treatment could be used as a disease activity marker to monitor the course of someone’s treatment.

But Burnett said more data on the approach are necessary. “This is a fairly small study, as it goes, for developing a screening test,” he said. “We need to see what its positive predictive value, negative predictive value, sensitivity, and specificity are in a bigger group.”

The road to a cure is even longer than the path to developing a screening test. Kommagani’s lab is now conducting more studies in mice to elucidate the pharmacokinetics and toxicology of 4HI before human trials can be attempted.

And as Burnett pointed out, although mouse models are great for experimentation and generating hypotheses, “We’ve seen way too many times in the past where something’s really exciting in a mouse model or a rat model or a monkey model, and it just doesn’t pan out in humans.”

Kommagani received funding from National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grants (R01HD102680, R01HD104813) and a Research Scholar Grant from the American Cancer Society. Burnett reported no financial conflicts of interest.

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

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

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

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

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

Primary care physicians (PCPs) play a key role in treating young patients as they progress through the “atopic march” from atopic dermatitis through food allergy, asthma, and allergic rhinitis. They can also help prevent the process from starting.

“The PCP is usually the first clinician a family with concerns about atopic conditions sees, unless they first visit urgent care or an emergency department after an allergic reaction to food. Either way, families rely on their PCP for ongoing guidance,” said Terri F. Brown-Whitehorn, MD, attending physician in the Division of Allergy and Immunology at the Center for Pediatric Eosinophilic Disorders and the Integrative Health Program at Children’s Hospital of Philadelphia.

“The most important thing PCPs can do is know that the atopic march exists, how it progresses over time, and what signs and symptoms to look for,” she told this news organization.
 

The Atopic March

The atopic march describes the progression of allergic diseases in a child over time, with atopic dermatitis and food allergy in infancy tending to be followed by allergic rhinitis and asthma into later childhood and adulthood.

Although the pathophysiology of the inflammation that precedes atopic dermatitis is unclear, two main hypotheses have been proposed. The first suggests a primary immune dysfunction leads to immunoglobulin E (IgE) sensitization, allergic inflammation, and a secondary disturbance of the epithelial barrier; the second starts with a primary defect in the epithelial barrier that leads to secondary immunologic dysregulation and results in inflammation.

Genetics, infection, hygiene, extreme climate, food allergens, probiotics, aeroallergens, and tobacco smoke are thought to play roles in atopic dermatitis. An estimated 10%-12% of children and 1% of adults in the United States have been reported to have the condition, and the prevalence appears to be increasing. An estimated 85% of cases occur during the first year of life and 95% before the age of 5 years.

“Atopy often, though not always, runs in families, so PCPs should inquire about the history of atopic dermatitis, IgE-mediated food allergies, allergic rhinitis, and asthma in the patient’s siblings, parents, and grandparents,” Brown-Whitehorn said.
 

Key Educators

PCPs treat the full gamut of atopic conditions and are key educators on ways families can help mitigate their children’s atopic march or stop it before it begins, said Gerald Bell Lee, MD, an allergist and immunologist at Children’s Healthcare of Atlanta and an associate professor in the Division of Allergy and Immunology at Emory University School of Medicine, Atlanta.

“Most parents who bring their infants with eczema to the PCP assume their child ate something that caused their rash. But the relationship between atopic dermatitis, a type of eczema, and food allergy is more complicated,” he added.

Lee said PCPs should explain to their patients what atopic dermatitis is, how it starts and progresses, and how families can help prevent the condition by, for example, introducing allergenic foods to infants at around 4-6 months of age.
 

Atopic Dermatitis

PCPs should inform parents and other caregivers to wash their hands before moisturizing their child, take care not to contaminate the moisturizer, and bathe their child only when the child is dirty.

“Soap removes protective natural skin oils and increases moisture loss, and exposure to soap and bathing is a main contributor to eczema,” said Lee. “Dry skin loses its protective barrier, allowing outside agents to penetrate and be identified by the immune system.”

“According to one hypothesis, parents may eat food, not wash their hands afterwards, then moisturize their baby. This unhygienic practice spreads food proteins from the adult’s meal, and possibly from contaminants present in the moisturizer, all over the baby’s body,” he added.

Lee said he and his colleagues discourage overbathing babies to minimize the risk for skin injury that begins the atopic march: “New parents are inundated with infant skincare messaging and products. But we need to weigh societal pressures against practicality and ask, ‘Is the child’s skin actually dirty?’ ”

Atopic dermatitis tends to appear on the extensor surfaces, face, and scalp in infants and around arm and leg creases in toddlers and older children. Severe forms of the condition can be more widely distributed on the body, said Aarti P. Pandya, MD, medical director of the Food Allergy Center at Children’s Mercy Kansas City and clinical assistant professor of pediatrics at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
 

Avoid Triggers, Minimize Flares

Triggers of eczema are varied and common. To help minimize flares, PCPs can encourage caregivers to avoid products with fragrances or dyes, minimize the use of soaps, and completely rinse laundry detergent from clothing and household items. “Advise them to keep fingernails short and control dander, pollen, mold, household chemicals, and tobacco smoke, as well as the child’s stress and anxiety, which can also be a trigger,” Lee said.

“Skin infections from organisms such as staph, herpes, or coxsackie can also exacerbate symptoms,” Brown-Whitehorn added. “PCPs can educate caregivers to avoid all known triggers and give them an ‘action plan’ to carry out when skin flares.”
 

Food Allergies

Parents may be unaware food allergens can travel far beyond the plate, Lee said. Researchers vacuuming household bedding, carpets, furniture, and other surfaces have detected unnoticeably tiny quantities of allergenic food proteins in ordinary house dust. Touching this dust appears to provide the main exposure to those allergens.

“According to the dual exposure to allergen hypothesis, an infant’s tolerance to antigens occurs through high-dose exposure by mouth, and allergic sensitization occurs through low-dose exposure through the skin,” he said. “As young as four to six months of age, even before eating solid food, a child develops eczema, has a leaky skin barrier, comes in contact with food, and develops a food allergy.”

IgE-mediated food allergies can begin at any age. “Symptoms occur when a food is ingested and the patient develops symptoms including but not limited to urticaria, angioedema, pruritus, flushing, vomiting, diarrhea, coughing, wheezing, difficulty breathing, presyncope, or syncope,” Pandya noted.

In the case of eosinophilic esophagitis, which may also be part of the atopic march, infants and toddlers often have challenging-to-treat symptoms of reflux, while school-age children have reflux and abdominal pain, and adolescents and adults may experience difficulty swallowing and impactions of food or pills, Brown-Whitehorn said.

To differentiate between food allergy and contact dermatitis, Lee suggested providers ask, “ ’Is the rash hives? If yes, is the rash generalized or in a limited area?’ Then consider the statistical probabilities. Skin problems after milk, egg, wheat, soy, peanut, tree nut, fish, shellfish, or sesame are likely due to IgE-mediated food allergy, but after ketchup or strawberry are probably from skin contact.”
 

Allergic Rhinitis and Asthma

“For asthma, ask about frequency of night cough and symptoms with exercise, laughing, or crying. For allergic rhinitis, look for runny nose, itchy eyes, or sneezing,” Brown-Whitehorn said.

Testing and Monitoring

Assessing the extent of eczema with the Eczema Area and Severity Index or the SCORing Atopic Dermatitis index takes time but may be necessary to obtain insurance coverage for treatments such as biologics.

Avoid ordering IgE food panels, which can result in false positives that can lead to loss of tolerance and nutritional deficiencies; psychological harm from bullying, anxiety, and decreased quality of life; and higher food and healthcare costs, Pandya said.

Treatments
Caregivers may be wary about treatments, and all the three experts this news organization spoke with stressed the importance of educating caregivers about how treatments work and what to expect from them.

“Early and aggressive atopic dermatitis treatment could prevent sensitization to food or aeroallergens, which could help prevent additional atopic diseases, including those on the atopic march,” Pandya said. “Topical steroids are considered first line at any age. Topical phosphodiesterase inhibitors are approved at 3 months of age and above. Topical calcineurin inhibitors are approved at 2 years of age and above. Wet wrap therapy and bleach baths can be effective. Other options include biologic therapy, allergen immunotherapy, and UV therapy.”

“Epinephrine auto-injectors can counteract food reactions. For allergic rhinitis, non-sedating antihistamines, steroidal nasal sprays, and nasal antihistamines help. Asthma treatments include various inhaled medications,” Brown-Whitehorn added.
 

When to Refer to Specialists

Involving an allergist, dermatologist, pulmonologist, or ear nose throat specialist to the patient’s care team is advisable in more challenging cases.

If a child is younger than 3 months and has moderate to severe atopic dermatitis, an underlying immune defect may be to blame, so an allergy and immunology assessment is warranted, Brown-Whitehorn said. “An allergist can help any child who has recurrent coughing or wheezing avoid the emergency room or hospitalization.”

“In pediatrics, we always try to find the medication, regimen, and avoidance strategies that use the least treatment to provide the best care for each patient,” Brown-Whitehorn added. “Children eat, play, learn, and sleep, and every stage of the atopic march affects each of these activities. As clinicians, we need to be sure that we are helping children make the best of all these activities.”

Brown-Whitehorn reported financial relationships with DBV Technologies and Regeneron Pharmaceuticals. Lee reported financial relationships with Novartis. Pandya reported financial relationships with DBV Technologies, Thermo Fisher Scientific, and Sanofi.
 

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

Physicians shared their views on frequently discussed (and sometimes controversial) topics ranging from romances with patients to age-related competency tests in the latest report from Medscape Medical News.

The report captured data from over 1000 full- or part-time US physicians across more than 29 specialties who were surveyed over a 3-month period in 2024.

Responsibility toward their patients was a clear priority among the doctors surveyed.

While around 6 in 10 physicians said they would immediately discharge a patient who refused to follow their treatment recommendations, 8% said they would wait, and 31% indicated they would keep the patient.

Asked whether physicians should have to undergo competency testing at a certain age, 30% of respondents said yes vs 22% no, and 48% felt it depended on multiple factors.

Most doctors (91%) said they would not accept a gift of substantial monetary or sentimental value from a patient, adhering to the AMA Code of Medical Ethics.

Big gifts “may signal psychological issues, and it is not fair to patients who can’t afford big gifts, since they may encourage better care,” said Jason Doctor, PhD, a senior scholar at the USC Leonard D. Schaeffer Center for Health Policy & Economics in Los Angeles, California. “It also taints the doctor-patient relationship, which should not involve large gifts of expectations of reciprocity.”

The vast majority of doctors said a romantic relationship with a patient still in their care was unacceptable, although 1% felt it would be OK, and 9% said, “it depends.”

When asked if they might withhold information about a patient’s condition if disclosure could do more harm than good, the majority of doctors said no. But 38% said it depended on the situation.

“This is how the profession and public expectations are evolving from the old paternalistic approach,” said Peter Angood, MD, president and CEO of the American Association for Physician Leadership.

Meanwhile, most doctors (62%) said that an annual flu shot should be mandatory for physicians who see patients. And a substantial majority of doctors surveyed agreed that taking care of their physical and mental health amounts to an ethical duty.

Around three in four physicians surveyed said felt periodic bias training was necessary for doctors.

“We all need refreshers about our own bias and how to manage it,” one respondent said. But another physician said, “I think we all know what appropriate behavior is and don’t need to add yet another CME course, ugh.”

Roughly equal shares of doctors surveyed felt some obligation to take at least some Medicaid patients or felt no societal obligation. The remaining 18% were willing to treat Medicaid patients once states streamlined the rules and improved reimbursements.

And finally, nearly all the survey respondents said physicians should advise patients on the risks of marijuana, notwithstanding the number of states and localities that recently have legalized pot or cannabis products.
 

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

Depending on one’s perspective, “mast cell activation syndrome (MCAS)” is either a relatively rare, narrowly defined severe allergic condition or a vastly underrecognized underlying cause of multiple chronic inflammatory conditions that affect roughly 17% of the entire population. 

Inappropriate activation of mast cells — now termed mast cell activation disease (MCAD) — has long been known to underlie allergic symptoms and inflammation, and far less commonly, neoplasias such as mastocytosis. The concept of chronic, persistent MCAS associated with aberrant growth and dystrophism is more recent, emerging only in the last couple of decades as a separate entity under the MCAD heading. 

Observational studies and clinical experience have linked signs and symptoms of MCAS with other inflammatory chronic conditions such as hypermobile Ehlers-Danlos Syndrome (EDS), postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and recently, long COVID. However, those conditions themselves are diagnostically challenging, and as yet there is no proof of causation.

The idea that MCAS is the entity — or at least, a key one — at the center of “a confoundingly, extraordinarily heterogeneous chronic multisystem polymorbidity” was the theme of a recent 4-day meeting of a professional group informally dubbed “Masterminds.” Since their first meeting in 2018, the group has grown from about 35 to nearly 650 multidisciplinary professionals. 

Stephanie L. Grach, MD, assistant professor of medicine at the Mayo Clinic, Rochester, Minnesota, gave an introductory talk about the importance of changing “the medical paradigm around complex chronic illness.” Much of the rest of the meeting was devoted to sharing approaches for managing MCAS comorbidities, including dysautonomia, hypermobility, and associated craniocervical dysfunction, and various other multi-system conditions characterized by chronic pain and/or fatigue. Several talks covered the use of agents that block mast cell activity as potential treatment. 

In an interview, Grach said “the meeting was an exciting example of how not only research, but also medicine, is moving forward, and it’s really cool to see that people are independently coming to very similar conclusions about shared pathologies, and because of that, the importance of overlap amongst complex medical conditions that historically have really been poorly addressed.”

She added, “mast cell activation, or mast cell hyperactivity, is one part of the greater picture. What’s important about the mast cell component is that of the multiple different targetable pathologies, it’s one that currently has potential available therapies that can be explored, some of them relatively easily.”

But Christopher Chang, MD, PhD, chief of the Pediatric Allergy and Immunology program, Joe DiMaggio Children’s Hospital, Hollywood, Florida, sees it differently. In an interview, he noted that the reason for disagreement over what constitutes MCAS is that “it doesn’t have a lot of objective findings that we can identify. ... We know that mast cells are important immune cells, just like all immune cells are important. It seems like whenever someone has unexplained symptoms, people try to blame it on mast cells. But it’s very hard to prove that.” 
 

Two Definitions Characterize the Illness Differently

One proposed “consensus” MCAS definition was first published in 2011 by a group led by hematologist Peter Valent, MD, of the Medical University of Vienna in Austria. It has been revised since, and similar versions adopted by medical societies, including the American Academy of Allergy, Asthma & Immunology (AAAAI). The most recent versions propose three core MCAS criteria: 

• Typical clinical signs of severe, recurrent (episodic) systemic (at least two organ systems) MCA are present (often in the form of anaphylaxis).
• The involvement of mast cells (MCs) is documented by biochemical studies, preferably an increase in serum tryptase levels from the individual’s baseline to plus 20% + 2 ng/mL.
• Response of symptoms to therapy with MC-stabilizing agents, drugs directed against MC mediator production, or drugs blocking mediator release or effects of MC-derived mediators.

The following year, a separate publication authored by Gerhard J. Molderings, MD, University of Bonn in Germany, and colleagues proposed a much broader MCAS definition. Also revised since, the latest “consensus-2” was published in 2020. This definition consists of one major criterion: “A constellation of clinical complaints attributable to pathologically increased MC activity, ie, MC mediator release syndrome.” This “constellation” involves conditions of nearly every organ system that, taken together, are estimated to affect up to 17% of the entire population. These are just a few examples: 

• Constitutional: Chronic fatigue, flushing, or sweats
• Dermatologic: Rashes or lesions
• Ophthalmologic: dry eyes
• Oral: Burning or itching in mouth
• Pulmonary: Airway inflammation at any/all levels
• Cardiovascular: Blood pressure lability or codiagnosis of POTS is common
• Gastrointestinal: Reflux, dysphagia, or malabsorption
• Genitourinary: Endometriosis, dysmenorrhea, or dyspareunia
• Musculoskeletal/connective tissue: Fibromyalgia or diagnosis of hypermobile EDS is common
• Neurologic: Headaches or sensory neuropathies
• Psychiatric: Depression or anxiety
• Endocrinologic: Thyroid disease or dyslipidemia
• Hematologic: Polycythemia or anemia (after ruling out other causes)

The diagnosis is made by fulfilling that major criterion, plus at least one objective assessment of pathologically increased release of MC mediators, including infiltrates, abnormal MC morphology, or MC genetic changes shown to increase MC activity. Other alternatives include evidence of above-normal levels of MC mediators, including tryptase, histamine or its metabolites, heparin, or chromatin A, in whole blood, serum, plasma, or urine. Symptomatic response to MC activation inhibitors can also be used but isn’t required as it is in the other definition. 
 

Underdiagnosis vs Overdiagnosis

Lawrence B. Afrin, MD, senior consultant in hematology/oncology at the AIM Center for Personalized Medicine, Westchester, New York, and lead author of the 2020 update of the broader “consensus-2” criteria, said in an interview, “we now know MCAS exists, and it’s prevalent, even though, for understandable and forgivable reasons, we’ve been missing it all along. ... If you see a patient who has this chronic, multisystem unwellness with general themes of inflammation plus or minus allergic issues and you can’t find some other rational explanation that better accounts for what’s going on ... then it’s reasonable to think to include MCAS in the differential diagnosis. If the patient happens not to fit the diagnostic criteria being advanced by one group, that doesn’t necessarily rule out the possibility that this is still going on.”

Afrin, along with his coauthors, faulted the narrower “consensus-1” definition for lacking data to support the “20% + 2” criteria for requiring the difficult determination of a patient’s “baseline” and for requiring evidence of response to treatment prior to making the diagnosis. Not all patients will respond to a given histamine blocker, he noted. 

But Lawrence B. Schwartz, MD, PhD, an author on both the Valent and AAAAI criteria, disagreed, noting that the narrower criteria “appear to have a high degree of specificity and sensitivity when the reaction is systemic and involves hypotension. Less severe clinical events, particularly involving the gastrointestinal or central nervous systems, do not have precise clinical or biomarker criteria for identifying mast cell involvement.” 

Added Schwartz, who is professor of medicine and chair of the Division of Rheumatology, Allergy, and Immunology and program director of Allergy and Immunology, Virginia Commonwealth University (VCU), Richmond, “when mast cell activation events occur only in the skin, we refer to it as chronic urticaria and in the airways or conjunctiva of allergic individuals as allergic asthma, rhinitis, and/or conjunctivitis. The absence of specific criteria for mast cell activation in the GI [gastrointestinal] tract or CNS [central nervous system] neither rules in mast cell involvement nor does it rule out mast cell involvement. Thus, more research is needed to find better diagnostic criteria.”

Schwartz also pointed to a recent paper reporting the use of artificial intelligence models to “quantify diagnostic precision and specificity” of “alternative” MCAS definitions. The conclusion was a “lack of specificity is pronounced in relation to multiple control criteria, raising the concern that alternative criteria could disproportionately contribute to MCAS overdiagnosis, to the exclusion of more appropriate diagnoses.”

During the meeting, Afrin acknowledged that the broader view risks overdiagnosis of MCAS. However, he also referenced Occam’s razor, the principle that the simplest explanation is probably the best one. “Which scenario is more likely? Multiple diagnoses and problems that are all independent of each other vs one diagnosis that’s biologically capable of causing most or all of the findings, ie, the simplest solution even if it’s not the most immediately obvious solution?”

He said in an interview: “Do we have any proof that MCAS is what’s underlying hypermobile Ehlers-Danlos or POTS or chronic fatigue? No, we don’t have any proof, not because anybody has done studies that have shown there to be no connection but simply because we’re so early in our awareness that the disease even exists that the necessary studies haven’t even been done yet.”

At the meeting, Afrin introduced proposals to turn the “Masterminds” group into a formal professional society and to launch a journal. He also gave an update on progress in developing a symptom assessment tool both for clinical use and to enable clinical trials of new drugs to target mast cells or their mediators. The plan is to field test the tool in 2025 and publish those results in 2026. 

Grach, Afrin, and Chang had no disclosures. Schwartz discovered tryptase and invented the Thermo Fisher tryptase assay, for which his institution (VCU) receives royalties that are shared with him. He also invented monoclonal antibodies used for detecting mast cells or basophils, for which VCU receives royalties from several companies, including Millipore, Santa Cruz, BioLegend, and Hycult Biotech, that are also shared with him. He is a paid consultant for Blueprint Medicines, Celldex Therapeutics, Invea, Third Harmonic Bio, HYCOR Biomedical, Jasper, TerSera Therapeutics, and GLG. He also serves on an AstraZeneca data safety monitoring board for a clinical trial involving benralizumab treatment of hypereosinophilic syndrome and receives royalties from UpToDate (biomarkers for anaphylaxis) and Goldman-Cecil Medicine (anaphylaxis).

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

As at-home, do-it-yourself (DIY) brain stimulation devices like transcranial direct current stimulation (tDCS) gain popularity for common psychiatric conditions like depression, anxiety, and posttraumatic stress disorder (PTSD), questions arise about their safety and efficacy.

However, the US Food and Drug Administration (FDA) has yet to “fully” clear any of these devices and has only granted breakthrough device designation to a few. In addition, most of the portable products don’t market themselves as medical interventions, putting them into a regulatory “gray area” that has little oversight.

This has led to a free-for-all environment, allowing individuals to purchase these products online and self-administer “treatment” — often without the guidance or even knowledge of their healthcare providers.

So how effective and safe are these noninvasive brain stimulators, and what guidance, if any, should clinicians provide to patients who are or are contemplating using them at home; what does the research show, and what are the ethical considerations?
 

What the Research Shows

Data from studies examining unsupervised at-home and use under medical supervision are mixed. Results from a recent randomized trial of more than 200 participants showed no significant difference in safety or efficacy between adjunctive at-home tDCS and at-home sham tDCS for depressive symptoms.

“To be fair, they did not find any unexpected safety issues. What they did find was that there was no clear signal that it worked,” said Noah S. Philip, MD, professor of psychiatry and human behavior, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Philip, who is also lead for mental health research at Brown’s Center for Neurorestoration and Neurotechnology, Providence, Rhode Island, and was not involved in the study, noted that while other research papers have shown more promising results for depression and other conditions such as adult attention-deficit/hyperactivity disorder (ADHD) and pain, they often are not placebo controlled or include large numbers of patients.

Still, he added the growing use of these devices reflects the fact that standard treatment often doesn’t meet patients’ needs.

“Broadly speaking, part of the hope with brain stimulation is that instead of taking a pill, we’re trying to more directly affect the brain tissues involved — and therefore, avoid the issue of having systemic side effects that you get from the meds. There’s certainly a hunger” for better interventions, Philip said.

tDCS involves a low-intensity electrical current applied through electrodes on the scalp in order to influence brain activity. Generally speaking, it emits less energy than other types of noninvasive brain stimulation, such as transcranial magnetic stimulation. “The trade-off is that’s it also a little harder to find a clear signal about how it works,” Philip said.

As such, he added, it’s important for clinicians to familiarize themselves with these devices, to ask about patient use, and to set up structured assessments of efficacy and adverse events.

Results from a randomized trial published last year in The Lancet showed no significant benefit for in-office use of tDCS plus a selective serotonin reuptake inhibitor vs sham tDCS for major depression.

On the other hand, a randomized trial published earlier this year in Brain Stimulation showed that older adults who received active tDCS had greater reductions in depressive and anxiety symptoms than those in the sham group.

In addition, results from a small study of eight participants published last year in SAGE Open Medicine showed adjuvant tDCS helped patients with refractory PTSD. Finally, a randomized trial of 54 veterans from Philip’s own team showed tDCS plus virtual reality was effective for combat-related PTSD.

Although there have also been several studies showing possible benefit of tDCS for Alzheimer’s disease, Gayatri Devi, MD, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, noted in a Medscape Neurology Decision Point that “the problem with all these studies is that they’re all very small, and there [are] so many different variables in terms of how you interpret response.”
 

On-Demand Brain Stim

As for at-home use, there’s now a wide offering of these types of devices available online, allowing an individual to apply daily brain stimulation via headsets, dispensing with the need to consult a clinician. Most are battery-powered and emit a low-level current.

Philip noted that there are essentially two ways to obtain such devices. Some are readily available from online stores, while others require a prescription, which typically includes guidelines on how to use the device.

So far, none of these portable products have been fully cleared by the FDA — although the agency did grant Breakthrough Device designation to Sooma Medical for its device to treat depression in 2023 and to Flow Neuroscience in 2022.

In August 2023, Flow announced that its device is now being reviewed for full FDA clearance on the basis of trial results showing at-home tDCS was “twice as effective” as antidepressants. The company received regulatory approval in Europe in 2019.

Other research has shown “encouraging” results for these at-home devices for conditions such as adult ADHD and pain relief with remote supervision.

Philip noted that more high-quality randomized controlled trials are definitely needed, with “a number of companies probably getting close to releasing data sometime soon.”

Is it possible that a placebo effect is at work here? “Yes, partially,” said Philip. Users often become more mindful of managing their depression and other conditions, which leads to behavior change, he said.
 

A Quick Fix for a Broken System?

Joseph J. Fins, MD, The E. William Davis Jr, MD, professor of Medical Ethics and chief of the Division of Medical Ethics at Weill Cornell Medicine, New York City, also believes there could be a placebo effect at play.

“It’s important that we don’t ascribe efficacy to a device without being aware of the placebo effect,” he said. That’s why more and larger, placebo-controlled trials are needed, he added.

There’s a multitude of reasons why patients may turn to at-home devices on their own, including drug shortages and the inability to see a psychiatrist in a timely manner.

“I think it speaks to the isolation of these folks that leads to them doing this on their own. These devices become a technological quick fix for a system that’s desperately broken. There’s nothing wrong with being a consumer, but at a certain point they need to be a patient, and they need to have a clinician there to help them,” he said.

Fins said that he also worries about regulatory oversight because of the way the devices are classified. He likened them to supplements, which, because they don’t make certain claims, are not regulated with the same stringency as other products and fall into an area “in between regulatory spheres.”

“I think we’re trying to take old regulatory frameworks and jerry-rig it to accommodate new and evolving technologies. And I think we need to have serious study of how we protect patients as they become consumers — to make sure there’s enough safety and enough efficacy and that they don’t get ripped off out of desperation,” Fins said.

As for safety, at-home devices are unlikely to cause physical harm — at least when used as intended. “The riskier situations happen when people build their own, overuse it, or use it in combination with drugs or alcohol or other factors that can produce unpredictable results,” Philip said.

He added that DIY-built products carry a higher risk for burns or excessive energy output. A 2016 “open letter” from a group of neurologists, published in Annals of Neurology, warned about the dangers of DIY tDCS.

In addition, Philip noted that he has seen instances where patients become manic after using at-home tDCS, especially when trying to improve cognition.

“We have seen a number of peculiar side effects emerge in those situations. Typically, it’s anxiety, panic attacks, and sensitivity to bright lights, in addition to the emergence of mania, which would require major psychiatric intervention,” he said.

“So, it’s important that if folks do engage with these sorts of things, it’s with some degree of medical involvement,” Philip added.
 

Ethical Considerations

Roy Hamilton, MD, professor of neurology, psychiatry, and physical medicine & rehabilitation at the University of Pennsylvania, in Philadelphia, said that in the setting of proper training, proper clinician communication, and proper oversight, he doesn’t view at-home tDCS as ethically problematic.

“For individuals who have conditions that are clearly causing them remarkable detriment to quality of life or to their health, it seems like the risk-benefit ratio with respect to the likelihood of harm is quite good,” said Hamilton, who is also the director of the Penn Brain Science, Translation, Innovation, and Modulation Center.

In addition, tDCS and other transcranial electrical stimulation techniques seem to have a better safety profile than “many of the other things we send patients home with to treat their pain,” he said.

On the other hand, this risk calculus changes in a scenario where patients are neurologically intact, he said.

The brain, Hamilton noted, exhibits functional differences based on the region undergoing stimulation. This means users should follow a specific, prescribed method. However, he pointed out that those using commercially available devices often lack clear guidance on where to place the electrodes and what intensity to use.

“This raises concerns because the way you use the device is important,” he said.

Hamilton also highlighted important ethical considerations regarding enhanced cognition through technology or pharmaceutical interventions. The possibility of coercive use raises questions about equity and fairness, particularly if individuals feel pressured to use such devices to remain competitive in academic or professional settings.

This mirrors the current issues surrounding the use of stimulants among students, where those without ADHD may feel compelled to use these drugs to improve performance. In addition, there is the possibility that the capacity to access devices that enhance cognition could exacerbate existing inequalities.

“Any time you introduce a technological intervention, you have to worry about discriminative justice. That’s where only people who can afford such devices or have access to specialists who can give them such devices get to receive improvements in their cognition,” Hamilton said.

Neither the American Academy of Neurology nor the American Psychiatric Association has established practice guidelines for tDCS, either for use in clinical settings or for use at home. Hamilton believes this is due to the current lack of data, noting that organizations likely want to see more approvals and widespread use before creating guidelines.

Fins emphasized the need for organized medicine to sponsor research, noting that the use of these devices is becoming a public health issue. He expressed concern that some devices are marketed as nonmedical interventions, despite involving medical procedures like brain stimulation. He concluded that while scrutiny is necessary, the current landscape should be approached without judgment.

Fins reported no relevant financial relationships. Philip reported serving on a scientific advisory board for Pulvinar Neuro and past involvement in clinical trials related to these devices and their use as home. Hamilton reported he is on the board of trustees for the McKnight Brain Research Foundation, which is dedicated to advancing healthy cognitive aging.
 

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

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Physicians who treat patients are potentially exposed to two opposing psychological processes: A positive feeling related to the experience of helping someone in need and, on the other hand, the adverse experience of seeing someone’s suffering and being frustrated about their inability to help. The ability to share the feelings of others is often referred to as empathy, while the ability to care for and show interest in others is the key aspect of compassion. Empathy makes it possible to share the positive and negative feelings of others in the same way: We can therefore feel happy when we indirectly share others’ joy and sad when we indirectly share others’ suffering.

Empathy in healthcare professionals is associated with patient satisfaction, diagnostic accuracy, adherence to treatment recommendations, clinical outcomes, clinical expertise, and physician retention. However, evidence indicates a tendency for empathy to decline during physicians’ training and specialization.
 

Estimating Empathy

Empathy studies are primarily based on observational data that include physician self-assessment or patient-perceived empathy. External evaluation of empathy by the recipient or observer is not the dominant approach, and a systematic review of the topic showed that, in 331 of the 470 studies examined (70.4%), individuals self-reported their level of empathy. The self-assessment system, particularly for doctors, is more likely to measure the doctor’s attitudes about empathy than empathy itself. The lack of correlation between physician and patient empathy assessments made it clear that patients cannot be disregarded when assessing physician empathy.

Consultation and Relational Empathy (CARE) is the primary assessment tool available to patients to measure physician empathy. It is a reliable and consistent system, particularly in primary care scenarios.

The CARE measure captures even small nuances of patient interactions with the physician and has been confirmed as a valuable tool in assessing the relational components of empathy.
 

Doctor-Patient Relationship

Communication with the physician is generally considered an important element of chronic pain care because it affects patient engagement and decision-making. A collaborative approach involving the patient and clinician in clinical decisions was associated with adherence to pain treatment and improved outcomes among patients with chronic lower back pain. The study conducted in a primary care setting of 1352 participants showed findings regarding physician empathy that did not necessarily involve a therapeutic alliance with the patient based on collaborative communication or expectation of a therapeutic effect of pharmacotherapy. Physician empathy remained the strongest factor associated with patient satisfaction, even after considering various potential confounders, including communication with the physician. In addition, ongoing empathy, especially when reported by patients with a long-term relationship with the physician, supported the hypothesis of a possible lasting effect on patient satisfaction.

Treating Chronic Pain

Empathy is an aspect of the doctor-patient relationship that may be particularly important in patients with chronic pain. A cohort study of 1470 patients with chronic low back pain analyzed whether and how it correlated with chronic pain outcomes. Patients reported their physician’s empathy at the time of enrollment using the CARE measure, which included 10 items on physician’s empathy characteristics during meetings. Physicians whose scores were 30 or higher (ie, rated as good, very good, or excellent in most items) were classified as very empathetic physicians (VEPs), while those whose scores were 29 or lower (ie, rated as poor or passable in most items) were classified as slightly empathetic physicians (SEPs).

Pain intensity was measured with a numerical rating scale (0-10) for the typical pain level within 7 days before each encounter. The long-term stability of CARE scores was assessed in patients who maintained the same physician for more than 24 months. The study showed the following results:

• The CARE score was inversely associated with pain intensity (P < .001).
• Pain intensity was lower in patients in the VEP group than those in the SEP group (6.3 vs 6.7; P < .001).
• The likelihood of having a more empathetic physician generally increased with the decrease in the cut point of the CARE score for greater or less empathy of the physician.
• The extent of the physician’s empathy effects exceeded that reported for nonpharmacological treatments, current opioid use, and lumbar spine surgery.
• The effects of the interaction of empathy with time tended to favor the VEP group with regard to pain but were not statistically significant.

Empathy is an essential aspect of the patient-physician relationship (particularly in delivering care), and these findings demonstrate its relevance in pain therapy. Empathy has high therapeutic value, compared with many pain treatments that are often recommended in clinical practice.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.

Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. He spoke with this news organization about his efforts to shape AI into a tool with practical applications in gastroenterology, what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
 

How did you first become involved in studying AI applications for GI conditions?

My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.

Leisa Thompson

I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?

I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.

I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
 

How did your early research go about trying to solve that problem?

My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.

I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.

Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
 

How did you convert the promise of CNN into tangible results?

The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.

In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.

Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.

Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.

To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.

What took us 3 years in 2016 would take about 3 weeks today.
 

You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?

We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.

The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.

For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.

Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.

Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.

Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
 

Were there any surprises in your work?

I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.

AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.

With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
 

Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?

Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.

We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.

The inevitability of AI-powered transformations in gastroenterology care became apparent.

Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.

AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
 

What does adaptation look like for gastroenterologists over the next handful of years?

Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.

Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.

That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.

A version of this article appeared on Medscape.com.

Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.

Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. He spoke with this news organization about his efforts to shape AI into a tool with practical applications in gastroenterology, what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
 

How did you first become involved in studying AI applications for GI conditions?

My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.

Leisa Thompson

I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?

I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.

I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
 

How did your early research go about trying to solve that problem?

My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.

I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.

Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
 

How did you convert the promise of CNN into tangible results?

The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.

In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.

Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.

Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.

To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.

What took us 3 years in 2016 would take about 3 weeks today.
 

You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?

We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.

The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.

For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.

Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.

Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.

Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
 

Were there any surprises in your work?

I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.

AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.

With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
 

Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?

Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.

We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.

The inevitability of AI-powered transformations in gastroenterology care became apparent.

Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.

AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
 

What does adaptation look like for gastroenterologists over the next handful of years?

Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.

Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.

That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.

A version of this article appeared on Medscape.com.

Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.

Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. He spoke with this news organization about his efforts to shape AI into a tool with practical applications in gastroenterology, what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
 

How did you first become involved in studying AI applications for GI conditions?

My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.

Leisa Thompson

I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?

I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.

I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
 

How did your early research go about trying to solve that problem?

My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.

I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.

Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
 

How did you convert the promise of CNN into tangible results?

The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.

In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.

Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.

Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.

To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.

What took us 3 years in 2016 would take about 3 weeks today.
 

You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?

We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.

The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.

For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.

Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.

Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.

Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
 

Were there any surprises in your work?

I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.

AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.

With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
 

Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?

Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.

We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.

The inevitability of AI-powered transformations in gastroenterology care became apparent.

Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.

AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
 

What does adaptation look like for gastroenterologists over the next handful of years?

Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.

Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.

That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO — Chimeric antigen receptor (CAR) T-cell therapies offer the tantalizing prospect of dramatically altering the outcome of lung cancers, but there are many hurdles to treating patients with them, according to experts.

These hurdles include finding the right targets, minimizing the risks of the treatment, and reducing the enormous burdens getting these therapies places on patients.

“Precision immunotherapy,” or unleashing the immune system in a highly specific manner, “is obviously, in a way, a holy grail” in lung cancer, said Martin Forster, MD, PhD, who cochaired a session on the topic at the World Conference on Lung Cancer (WCLC) 2024.

He underlined, however, that “immunology is very complex, as is cancer biology,” and consequently, there are different avenues being explored, including CAR T-cell therapies, T-cell receptor therapies, and tumor-infiltrating lymphocytes, among others.

Antibody technology is also being harnessed to target chemotherapy, via antibody-drug conjugates, noted Forster, who is clinical lead of the early phase clinical trials programme at University College London in England.

Moreover, investigators are looking at combining various therapies, such as immune checkpoint inhibitors with T cell–engaging approaches.

He highlighted, however, that the ideal target for these approaches is something that is recognized by the immune system as being foreign, but is found within the cancer, “and you also want it ideally to be in all of the cancer cells.”

A good example is a clonal change, meaning an early evolutionary genetic alteration in the tumor that is present in all the cells, Forster said.
 

Identifying the Right Target

“One of the big challenges in all forms of targeted immunotherapy is around selecting the target and developing the right product for the right target,” Forster emphasized.

“This concept works really well in hematological malignancies” but is “proving to be more challenging to deliver within solid malignancies,” he added.

“The reason why so many lung tumors are resistant to immunotherapy is because they ‘re immunologically cold,” Roy Herbst, MD, PhD, Department of Medical Oncology, Yale Comprehensive Cancer Center, New Haven, Connecticut, said in an interview.

“There are no T cells in the tumor,” he explained, so it “doesn’t really matter how much you block checkpoint inhibitors, you still have to have a T cell in there in order to have effect.”

To overcome this problem CAR T-cell therapies are engineered to target a tumor, Herbst continued, but that “is a little hard in lung cancer because you need to have a unique antigen that’s on a lung tumor that’s not present on normal cells.”

Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia, Pennsylvania, agreed, saying that there is “a lot of excitement with CAR T-cell therapies, and the promise of cure,” but “the biology is not as simple as we think.”

“For example, it’s not as simple as CD20 or CD19 targeting,” she said in an interview. “Most of the antigens that are being targeted in the solid tumor world, unfortunately, are also expressed on normal tissue. So there is always this potential for toxicity.”
 

A Question of Time

Another aspect of CAR T-cell therapy that is proving difficult is its delivery.

Forster outlined that the process involves first leukapheresis, in which T cells are obtained from a blood draw. These are then genetically modified to express chimeric antigen receptors before being multiplied in the laboratory and introduced to the patient.

This process can take several weeks, during which patients may require bridging treatment, such as chemotherapy or radiotherapy, to keep their cancer under control. “Sometimes, patients with solid tumors who are in later lines of therapy may not have the luxury of time to be able to wait for all of these steps,” Aggarwal said.

There is also the question of whether a bespoke treatment can be scaled up so that it can be delivered to more patients in a more timely manner.

“There are certainly lessons to be learned from use of off-the-shelf CAR T-cell products” in hematologic malignancies, she noted, “but we’re just not there yet in lung cancer.”
 

Life-Threatening Toxicities

To improve the chances of engraftment when the CAR T cells are introduced, patients will require prior lymphodepletion with chemotherapy.

This, Forster said, is a “relatively intensive part of treatment.” However, “if you just give immune cells to somebody, when the host body is already full of immune cells,” the CAR T cells are unlikely to engraft, and “so you need to create space for those cells to develop.”

“What you want is not an immediate effect” but rather an immune “memory” that will give an ongoing benefit, he underscored.

Many patients will need to stay in the hospital one or more nights “because when you bring T cells to a tumor, you get cytokine release syndrome [CRS],” Herbst said. This can cause hypotension, fever, and chills, similar to a viral response.

“So patients can get sick,” which in turn requires treatment and follow-up. That puts a “big burden on the health system” and is a major issue, Herbst said.

Patients are also at a risk for “significant neurotoxicity,” said session cochair Amy Moore, PhD, vice president of Global Engagement and Patient Partnerships, LUNGevity Foundation, Chicago. This, alongside CRS, “can be life threatening for our patients.”

Lengthy hospital stays also have a psychosocial impact on the patient and their quality of life, she emphasized, especially when they are treated in a center far away from family and loved ones.

“We’ve also heard anecdotally some reports recently of secondary malignancies” with CAR T cell and other therapies, and that’s something that needs to be monitored as more patients go on these treatments, she said.
 

‘At What Cost’ to Patients?

The difficulties faced by patients in receiving CAR T-cell therapy go far beyond the practicalities of generating the cells or the risks associated with lymphodepletion, however.

“These therapies are extraordinarily expensive,” although that has to be weighed against the cost of years of ongoing treatment with immunotherapy, Moore said.

Moreover, as CAR T-cell therapies are a “last resort” option, patients have to “exhaust all other treatments” before being eligible, she continued. There’s significant prior authorization challenges, which means patients “have to go through many hurdles before they can qualify for treatment with these therapies.”

This typically involves having numerous laboratory tests, which can add up to out-of-pocket expenses for patients often reaching tens of thousands of dollars, Moore said.

Another issue is that they must be administered in certified treatment centers, and there are a limited number of those in the United States, she added.

This increases the risk of heightening disparities, as patients are “forced to travel, seek lodging, and have meal expenses,” and the costs “are not trivial,” Moore underlined. “It can rack up quickly and mount to $10,000 or more.”

For physicians, there are difficulties in terms of the logistics of following up with those patients who need to be treated at centers on the other side of the country, uncertainties around reimbursement, and restrictions in terms of staff time and resources, among others.

“I’m as excited as you are at the science,” but it is the implementation that is at issue, Moore said. In other words, there is the offer of a cure with CAR T-cell therapy, but “at what cost?”

“For patients, these considerations are real and they’re significant” and “we have to ensure that what we’re doing is in service of people with cancer,” she emphasized.

No funding was declared. Aggarwal declared relationships with Genentech, Celgene, AstraZeneca, Daiichi Sankyo, Turning Point, Janssen, Pfizer, Lilly, Merck, Regeneron/Sanofi, Eisai, BeiGene, Boehringer Ingelheim, Blueprint Genetics, and Shionogi. Forster declared relationships with AstraZeneca, Boehringer Ingelheim, Merck, MSD, Achilles, Amgen, Bayer, Bristol-Myers Squibb, Celgene, EQRx, GSK, Immutep, Janssen, Merck, Oxford Vacmedix, PharmaMar, Roche, Takeda, Syncorp, Transgene, and Ultrahuman. Moore declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to the continuously improving treatment options for cancer, the number of cancer survivors is increasing, and a large proportion of survivors is confronted with the long-term effects of cancer treatment. Especially for young patients, the question of the impact of therapy on fertility arises.

Dose adjustment or modification of the treatment regimen can achieve a lot. But experts at the congress of the European Society for Medical Oncology (ESMO) 2024 noted that knowledge about newer treatment options like immunotherapies is still insufficient.
 

Therapy Selection

The question of preserving fertility must be considered when deciding on the appropriate treatment, said Matteo Lambertini, MD, PhD, medical oncology consultant at the University of Genoa in Genoa, Italy. A patient’s age, the type of therapy, and the dose are crucial in determining whether or how much fertility is affected. “Preserving fertility is also an aim of cancer therapy,” he said.

Lambertini, who is also a member of the ESMO Guideline Group on fertility preservation in cancer patients, referred to the 2020 ESMO guidelines, which list the gonadotoxicity of a substance depending on the treatment regimen and the patient’s age.

Isabelle Demeestere, MD, PhD, director of the research lab for human reproduction at the Erasmus Hospital of the Free University of Brussels in Brussels, Belgium, pointed out the limitations of general guidelines. “Therapies change over time, and a classification must be updated regularly.”

Knowledge gaps related to well-known therapies and many novel options persist. “For many FDA-approved medications, there are either no fertility data or only preclinical data available,” she added.
 

Chemotherapies and Immunotherapies

Chemotherapies with alkylating or platinum-containing substances are known for their effects on oocytes, follicle maturation, and spermatogenesis, said Demeestere.

Chemotherapy is gonadotoxic and leads to a temporary decrease in sperm quality or temporary azoospermia in men.

These effects, however, can lead to permanent azoospermia and endocrine disorders, depending on the dose, duration, or combination with radiation, said Demeestere.

Cryopreservation of sperm should always be performed before starting treatment. For high-risk patients who are prepubertal, samples of testicular tissue are taken.

In women, chemotherapy affects primordial follicles and follicle maturation through DNA damage. This process results in severe or temporary amenorrhea, a temporary or permanent decrease in egg reserve, and ultimately premature egg insufficiency.

Novel immunotherapies also influence fertility, presumably through interactions of the immune system with the reproductive organs. But insufficient data are available, according to Lambertini, who emphasized that “these data are urgently needed, especially for young patients with cancer.”

In a mouse model, immune checkpoint inhibitors affected ovarian function, and the inflammatory reaction in humans can affect fertility. No long-term data are available for women yet, however, explained Demeestere. The effects of other therapeutics such as PARP, CDK4/6, or tyrosine kinase inhibitors, as well as monoclonal antibodies like trastuzumab, are only seen sporadically.

In the PENELOPE-B phase 3 study, the CDK4/6 inhibitor palbociclib did not affect ovarian function, even though the cyclin-dependent kinases play an important role in mitotic arrest, said Demeestere.
 

Adjusting the Regimen

In a PET-guided approach, Demeestere’s research team investigated the effects of dose reduction or adjustment of the treatment regimen of procarbazine and cyclophosphamide on the fertility of patients younger than 45 years with advanced Hodgkin lymphoma.

By regularly controlling tumor growth with PET, the treatment could be adjusted so that the effect on egg reserve or spermatogenesis was significantly reduced and loss of fertility could be prevented.

During the 5-year follow-up period, the ovarian function of participating women was assessed by the serum concentration of follicle-stimulating hormone (FSH), estradiol, and anti-Müllerian hormone (AMH) to evaluate egg reserve. In men, testicular function was assessed at the beginning of the study. At the end of treatment, sperm analysis and FSH and testosterone levels were checked.

Demeestere and colleagues demonstrated that dose reduction or altering the treatment regimen for patients who responded early to treatment (determined by PET-guided monitoring) reduced the risk for gonadotoxicity from 46% to 14.5%. That is, the risk was reduced by more than half.

FSH and AMH correlated with the patient’s age and the dose of the alkylating agent. In men, sperm parameters recovered after dose or agent adjustment compared with the unchanged treatment regimen.

Newer results from the PHERGain study in women with early human epidermal growth factor receptor 2–positive breast cancer also provided hope, according to Demeestere. Under PET-guided control, chemotherapy could be reduced.
 

More Data Needed

The new treatment options pose a challenge to preserving fertility during cancer treatment, said Demeestere.

For new targeted therapies, uniform recommendations cannot be issued because of the lack of data and varying treatment durations. Still, the new therapies are safer than chemotherapy.

The need to collect data on fertility and long-term effects in cancer survivors in clinical studies is also reflected in the literature, according to Demeestere. “There are more review articles on this topic than clinical studies.”
 

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.