AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

AMSTERDAM — A proteomics study designed to determine why some patients with atopic dermatitis (AD) respond quickly to dupilumab, others respond more slowly, and the remainder do not respond at all demonstrated that molecular responses in these three groups are very different.

A discovery that could lead to personalizing therapies, the data identified “distinct systemic biomarker profiles,” according to Ester Del Duca, MD, an instructor in the Laboratory of Inflammatory Skin Diseases at the Icahn School of Medicine at Mount Sinai, New York City.

The study was conducted with 67 patients with AD and 16 healthy controls. Serum was collected at two timepoints: An average of 20 weeks after starting dupilumab, then at a mean interval of about 9 months later. At these timepoints, called follow-up 1 and 2, a panel of more than 600 proteins, including unique markers for immunologic, cardiovascular, and neurologic activity, were evaluated.

The criterion for differentiating the three response groups was an Investigator Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (or at least a 2-point IGA reduction from baseline). Early responders were those who met the criterion at both follow-ups, late responders were those who met this criterion only at the second follow-up, and nonresponders never met the criterion.

“There were no significant differences at baseline in clinical severity, past medical history, or patient characteristics,” said Del Duca, who presented these data in a late breaking news session at the European Academy of Dermatology and Venereology (EADV) 2024 Congress.

Of the 67 patients with AD, 39 were early responders, 11 were late responders, and 17 were nonresponders.

The differences in proteomics were marked. For early responders, there was an early normalization of the proteome, reported Del Duca, illustrating the differences in the proteome of the three groups with a color-coded chart of protein up-regulation and down-regulation relative to healthy controls. The normalization of the proteome persisted in early responders when assessed at the second follow-up.

In the late responders, the proteome dysregulation was substantial relative to healthy controls at the first follow-up, but there was considerable improvement by the second follow-up. Although the change at the second follow-up was still not as robust as that seen in the early responders at either follow-up, Del Duca described the proteomic profile as a 45% improvement from the first follow-up.

In contrast, nonresponders showed worsening in their blood proteome from follow-up 1 to 2. Nonresponders at first follow-up showed up-regulation relative to healthy controls for many proteins associated with the Th1 response, such as interferon gamma, CXCL9, and CXCL10, and Th2 response, such as interleukin-4 and Th17/22, and these did not normalize or worsen by the second follow-up.

“Uniquely to nonresponders, key Th1 biomarkers remained significantly up-regulated relative to controls at both follow-up 1 and 2,” with a P value < .05, Del Duca reported.

To achieve normalization of the proteome as defined by healthy controls, both up-regulation and down-regulation of protein activity were required, although more up-regulations than down-regulations were observed.

When evaluating the proteome changes most implicated in immunoregulation, the investigators were able to show a correlation between worsening in the proteome and greater severity of AD as defined by IGA, Eczema Area and Severity Index, and body surface area involvement.

“Spearman analysis revealed strong and positive correlations between improvements in biomarkers at follow-up 1 and 2 with improvements in clinical markers,” Del Duca said. As examples, she noted favorable changes in biomarkers specifically associated with T cells, dendritic cells, and natural killer cells as clinical outcomes improved.

Conversely, the worsening in T-cell activation among nonresponders, particularly Th1 biomarkers, also tracked with increasing AD symptoms over time.

The implications of the research are broad, and most importantly, it shows that therapeutic targets are likely to differ between patients with AD, according to Del Duca. Although proteomic studies have not yet been conducted with other treatments, these might provide further insight about how patients with AD differ in response across other drugs.

This is important work, according to Brigitte Dréno, MD, PhD, head of the Department of Dermatology, Nantes University Hospital in France. As moderator of the late-breaking news session, she suggested that there are many potential messages from these data, not least that treatment of AD likely involves targeting cytokines beyond those affected by dupilumab in at least some patients.

When Dréno asked Del Duca about what could be surmised about changes from baseline before treatment to the first follow-up, Del Duca said that the study was retrospective, so baseline data were not available.

This is an important missing piece of this investigation, according to Dréno.

“As you move this work forward,” she said that it would be “very important” to determine “if there are predictive markers for evaluating which patients will respond.”

This is a small study with many additional variables to consider in order to develop a clinically useful tool, Del Duca noted. However, this work not only has the potential to guide treatment selection but the biomarkers up-regulated in nonresponders are already “suggesting potential targets for refining therapeutic strategies,” she said.

The study received funding from Bristol-Myers Squibb. Del Duca reported no financial relationships with industry. Dréno reported financial relationships with La Roche–Posay, Pierre Fabré, and Galderma.

A version of this article appeared on Medscape.com.

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

Clinicians receive conflicting advice on whether to order blood tests to screen for lipids in children. A new study could add to the confusion. Researchers found that a combination of physical proxy measures such as hypertension and body mass index (BMI) predicted the risk for future cardiovascular events as well as the physical model plus lipid labs, questioning the value of those blood tests.

Some medical organizations advise screening only for high-risk children because more research is needed to define the harms and benefits of universal screening. Diet and behavioral changes are sufficient for most children, and universal screening could lead to false positives and unnecessary further testing, they said.

Groups that favor lipid tests for all children say these measurements detect familial hypercholesterolemia (FH) that would not otherwise be diagnosed, leading to treatment with drugs like statins and a greater chance of preventing cardiovascular disease (CVD) in adulthood.

Researchers from the new study said their findings do not address screenings for FH, which affects 1 in 250 US children and puts them at a risk for atherosclerotic CVD.
 

Recommending Blood Tests in Age Groups

One of the seminal guidelines on screening lipids in children came from the National Heart, Lung, and Blood Institute (NHLBI), which in 2011 recommended children undergo dyslipidemia screening between the ages of 9 and 11 years and again between 17 and 21 years. Children should receive a screening starting at age 2 years if they have a family history of CVD or dyslipidemia or have diabetes, an elevated BMI, or hypertension. The American Academy of Pediatrics shortly followed suit, issuing similar recommendations.

Screening for the two subsets of ages was an expansion from the original 1992 guidelines from the National Cholesterol Education Program, which recommended screening only for children with either a family history of early CVD or elevated total cholesterol levels.

A 2011 panel for the NHLBI said the older approach identified significantly fewer children with abnormal levels of low-density lipoprotein cholesterol (LDL-C) than the addition of two age groups for screening, adding that many children do not have a complete family history. The American College of Cardiology and American Heart Association later supported NHLBI’s stance in their joint guidelines on the management of cholesterol.

Mark Corkins, MD, chair of the AAP’s Committee on Nutrition, told Medscape Medical News that if children are screened only because they have obesity or a family history of FH, some with elevated lipid levels will be missed. For instance, studies indicate caregiver recall of FH often is inaccurate, and the genetic disorder that causes the condition is not related to obesity.

“The screening is to find familial hypercholesterolemia, to try to find the ones that need therapy,” that would not be caught by the risk-based screening earlier on in childhood, Corkins said.
 

Only Screen Children With Risk Factors

But other groups do not agree. The US Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against screening for lipid disorders in asymptomatic children and teens.

The group also said it found inadequate evidence that lipid-lowering interventions in the general pediatric population lead to reductions in cardiovascular events or all-cause mortality once they reached adulthood. USPSTF also raised questions about the safety of lipid-lowering drugs in children.

“The current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger,” the panel wrote.

The American Academy of Family Physicians supports USPSTF’s recommendations.
 

Low Rate of Screening

While the uncertainty over screening in children continues, the practice has been adopted by a minority of clinicians.

A study published in JAMA Network Open in July found 9% of 700,000 9- to 11-year-olds had a documented result from a lipid screening. Among more than 1.3 million 17- to 21-year-olds, 13% had received a screening.

As BMI went up, so did screening rates. A little over 9% children and teens with a healthy weight were screened compared with 14.7% of those with moderate obesity and 21.9% of those with severe obesity.

Among those screened, 32.3% of 9- to 11-year-olds and 30.2% of 17- to 21-year-olds had abnormal lipid levels, defined as having one elevated measure out of five, including total cholesterol of 200 mg/dL or higher or LDL-C levels of 130 mg/dL or higher.

Justin Zachariah, MD, MPH, an associate professor of pediatrics-cardiology at Baylor College of Medicine in Houston, spoke about physicians screening children based only on factors like obesity during a presentation at the recent annual meeting of the American Academy of Pediatrics. He cited research showing roughly one in four children with abnormal lipids had a normal weight.

If a clinician is reserving a lipid screening for a child who is overweight or has obesity, “you’re missing nearly half the problem,” Zachariah said during his presentation.

One reason for the low rate of universal screening may be inattention to FH by clinicians, according to Samuel S. Gidding, MD, a professor in the Department of Genomic Health at Geisinger College of Health Sciences in Bridgewater Corners, Vermont.

For instance, a clinician has only a set amount of time during a well-child visit and other issues may take precedence, “so it doesn’t make sense to broach preventive screening for something that could happen 30 or 40 years from now, vs this [other] very immediate problem,” he said.

Clinicians “are triggered to act on the LDL level, but don’t think about FH as a possible diagnosis,” Gidding told Medscape Medical News.

Another barrier is that in some settings, caregivers must take children and teens to another facility on a different day to fulfill an order for a lipid test.

“It’s reluctance of doctors to order it, knowing patients won’t go through with it,” Gidding said.

Gidding is a consultant for Esperion Therapeutics. Other sources in this story reported no relevant financial conflicts of interest.
 

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

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

AMSTERDAM — Following the report of results from a randomized trial in which a topically applied Janus kinase (JAK) inhibitor was highly active in patients with mild to moderate hidradenitis suppurativa (HS), an open-label extension showed that 16 more weeks of treatment on as-needed basis provided complete or near complete clearance of lesions in up to 38.5% of patients.

“Ruxolitinib cream may be a novel approach to address an unmet medical need in the treatment of milder HS for which there are no currently approved treatments,” reported Martina L. Porter, MD, assistant professor of dermatology, Harvard Medical School, and Beth Israel Deaconess Medical Center, both in Boston, Massachusetts.

In the earlier 16-week, double-blind, randomized period of this phase 2b study, 69 adults with mild to moderate HS were randomized to 1.5% ruxolitinib cream or vehicle, applied twice daily for 16 weeks. The new results are from the open-label extension period, where those on the vehicle were crossed over to topical ruxolitinib and treatment was continued for another 16 weeks.
 

Over 80% Meet Primary Endpoint at 32 Weeks

Entry criteria for the study included Hurley stage I or II HS with no draining tunnels. Hurley stage III patients were not eligible. Patients had to have an abscess or inflammatory nodule (AN) count of 3 lesions concentrated in a single anatomic area or up to 10 lesions if disseminated. The median AN count of those enrolled was 5.4. 

In the randomized portion of the study and in the open-label extension, the recommendation for application was to apply the medication to nodules and a 1-cm area of surrounding skin. As-needed treatment was only recommended in the extension portion of the study and rescue medication was not allowed.

The goal of the open-label extension was to evaluate how long the improvements were sustained, according to Dr. Porter, who presented the results at the 2024 European Academy of Dermatology and Venereology (EADV) meeting.

The primary endpoints of AN50, signaling at least a 50% reduction in AN count from baseline, among those initially randomized to ruxolitinib cream climbed slightly from 79.2% at the end of 16 weeks to 81.0% at the end of 32 weeks.

This shows that the benefits recorded in the randomized phase of the trial were sustained during the open-label extension, Dr. Porter said. 

For those randomized to vehicle, there was a substantial response of 56.3% for AN50 during the randomized portion of the study, but catchup in the vehicle group to those on active therapy occurred rapidly over the open-label extension. By the end of 32 weeks, the score among the crossover patients slightly exceeded that of those on continuous therapy (88.5% vs 81.0%).

AN75 responses at week 32 were 66.7% and 61.5% in the continuous arm and crossover arm, respectively. The proportion of patients reaching an AN90 or AN100 response, meaning clear or almost clear, were 19% and 38.5%, in continuous treatment and crossover arms, respectively.

One of the secondary endpoints was the HS Clinical Response 50, indicating at least a 50% reduction in the AN count with no increase in abscesses or draining fistulae. At 32 weeks, the proportions of patients who met this endpoint were 81.0% and 88.5% in the continuous treatment and crossover arms, respectively. 

The mean reduction in International HS Severity Scoring System scores from baseline were 4.1 and 4.5 in the continuous treatment and crossover arms, respectively. 
 

Patients in the Study Mostly Women, 42% Black Individuals

Most (94%) of the participants were women; about 45% and 42% were White and Black individuals, respectively. Most of the remaining patients were Asian individuals. The median age at entry was 29 years, and the mean body mass index was approximately 34 kg/m². A substantial proportion of patients had systemic comorbidities, according to Dr. Porter, who noted that about 25% had anxiety, depression, or both.

“This phenotype — a high proportion of women with nodules but no draining tunnels and a substantial number of comorbidities — is one we often see in patients with mild HS,” Dr. Porter said.

The safety and tolerability profile of ruxolitinib cream was quite good, according to Dr. Porter, who noted that there were fewer treatment-related adverse events in the open-label extension. Overall, the number of treatment-related adverse events (3.6%), including application site reactions leading to discontinuation (1.8%) was low. 

Although there is a growing list of therapies now approved for HS, Dr. Porter emphasized that all have been developed for moderate to severe disease. She suggested that there is a sizable group of patients with mild disease for whom such therapies as biologics might not be warranted even if symptom relief is needed.

Given this unmet need, she said phase 3 trials are warranted to confirm the benefits and the safety of a topical therapy that can be used as needed to control intermittent HS flares.

Asked to comment, the lead author of a recently published review article on the “evolving treatment landscape” of HS, James G. Krueger, MD, professor in clinical investigation at Rockefeller University, New York City, agreed that there is an unmet need for effective and safe therapies in milder HS.

“I agree with the premise,” said Dr. Krueger, indicating that phase 3 data will be essential to confirm the promise of this approach. Dr. Krueger, who did not hear the results presented at the EADV meeting, listed several JAK inhibitors in his review that have shown promising efficacy as oral agents and support JAK signaling as a target of HS treatment. 

Topical ruxolitinib (Opzelura) is currently approved in the United States for treating nonsegmental vitiligo in patients aged ≥ 12 years and for mild to moderate atopic dermatitis in patients aged ≥ 12 years. In Europe, it is approved for treatment of nonsegmental vitiligo with facial involvement in patients aged ≥ 12 years. 

Dr. Porter reported no potential conflicts of interest. Dr. Krueger reported financial relationships with more than 25 pharmaceutical companies not including Incyte, which is developing ruxolitinib cream.

A version of this article appeared on Medscape.com.

The American Heart Association (AHA) has issued a new scientific statement on the link between heart failure, atrial fibrillation, and coronary heart disease and the increased risk for cognitive impairment and dementia.

The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.

The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.

Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.

And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.

The statement was published online in Stroke.
 

Bridging the Research Gap

It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.

However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.

“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.

Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.

A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.

Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.

“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
 

Robust Heart-Brain Connection

The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.

The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.

“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.

This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.

“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.

However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”

For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
 

More Research Needed

While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.

Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.

More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.

“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.

More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.

They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
 

‘An Important Step’

Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.

She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”

This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.

But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.

No relevant conflicts of interest were disclosed.

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

The American Heart Association (AHA) has issued a new scientific statement on the link between heart failure, atrial fibrillation, and coronary heart disease and the increased risk for cognitive impairment and dementia.

The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.

The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.

Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.

And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.

The statement was published online in Stroke.
 

Bridging the Research Gap

It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.

However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.

“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.

Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.

A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.

Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.

“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
 

Robust Heart-Brain Connection

The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.

The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.

“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.

This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.

“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.

However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”

For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
 

More Research Needed

While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.

Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.

More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.

“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.

More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.

They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
 

‘An Important Step’

Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.

She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”

This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.

But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.

No relevant conflicts of interest were disclosed.

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

The American Heart Association (AHA) has issued a new scientific statement on the link between heart failure, atrial fibrillation, and coronary heart disease and the increased risk for cognitive impairment and dementia.

The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.

The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.

Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.

And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.

The statement was published online in Stroke.
 

Bridging the Research Gap

It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.

However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.

“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.

Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.

A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.

Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.

“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
 

Robust Heart-Brain Connection

The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.

The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.

“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.

This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.

“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.

However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”

For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
 

More Research Needed

While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.

Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.

More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.

“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.

More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.

They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
 

‘An Important Step’

Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.

She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”

This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.

But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.

No relevant conflicts of interest were disclosed.

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

The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.

Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.

Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.

Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.

Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
 

Increasing Incidence Among Younger Women

Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.

“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, coauthor of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”

Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
 

Addressing Health Inequities

The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.

Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.

“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added coauthor Cherie C. Hill, MD, FACOG.

ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.

Zaritsky and Hill reported no conflicts of interest.
 

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

VIENNA, AUSTRIA — The appropriate dose of pancreatic enzyme replacement therapy (PERT) for exocrine pancreatic insufficiency (EPI) depends on the root cause of the insufficiency, according to results of a prospective study using European registry data. 

Specifically, patients with EPI caused by pancreatic cancer or pancreatectomy need significantly more enzyme replacement than patients with insufficiency caused by chronic pancreatitis and acute pancreatitis. The need to add a proton pump inhibitor (PPI) to achieve the therapeutic goal also varies by condition, the study showed. 

World Pancreatic Cancer Coalition

One of the main symptoms of EPI is malnutrition, and successful PERT is defined as the resolution of nutritional deficiencies and relief of symptoms and signs associated with insufficiency, said study lead Enrique Domínguez Muñoz, MD, director of the department of gastroenterology and hepatology at University Hospital of Santiago de Compostela, Spain. 

Our findings show that, “in order to achieve this, enzyme dose escalation and sometimes additional treatment with a [PPI] should be applied as required by the individual”, he reported in a presentation at the United European Gastroenterology (UEG) Week 2024.

Therefore, having dose recommendations for PERT for different causes of EPI is very helpful, said Domínguez Muñoz.

Pancreatic enzyme preparations, specifically pancreatin, are the recommended first-line treatment for EPI, but the initial doses of PERT vary depending on the patient’s age (whether adult or child), the severity of the insufficiency, and the fat content of the meal eaten. 

Domínguez Muñoz and colleagues wanted to explore whether — and how — the severity of EPI varied with different diseases, therefore varying the optimal dose of PERT. 
 

Optimal Dosing to Achieve Therapeutic Goal 

The prospective study drew on data from a European multicenter registry of patients diagnosed with EPI being treated with PERT in expert centers. 

The researchers evaluated the dose of PERT required to achieve symptom relief and normalization of the nutritional status in adult patients with EPI secondary to different pancreatic diseases and conditions. The percentage of patients who required the addition of a PPI to PERT to achieve the therapeutic goal was also determined. 

Decisions on the initial enzyme dose (including the addition of a PPI) and any necessary adjustments during follow-up to achieve the therapeutic goal were made by the participants’ clinicians.

A total of 678 patients (mean age, 61.2 ± 13.8 years; 63.6% male) were stratified according to disease: 50% had chronic pancreatitis, 10% had acute pancreatitis, 17% had undergone pancreaticoduodenectomy, 15% had pancreatic cancer, and 8% had another pancreatic condition. 

To achieve the therapeutic goal, the median optimal enzyme doses with the main meal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy, were 40,000, 50,000, 70,000, and 75,000 Ph.U, respectively. The respective optimal daily enzyme doses were 100,000, 150,000, 210,000, and 225,000 Ph.U. 

The highest enzyme doses required with the main meal to achieve the therapeutic goal for patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and pancreaticoduodenectomy were 125,000, 210,000, 175,000, and 210,000 Ph.U, respectively. The respective highest daily enzyme doses were 400,000, 625,000, 675,000, and 750,000 Ph.U. 

The need for additional therapy with twice-daily PPI to achieve the therapeutic goal also varied according to the underlying disease. It was administered to 44.1% of patients with acute pancreatitis, 37.2% of patients with chronic pancreatitis, 78.8% of patients with pancreatic cancer, and 74.1% of patients who had undergone pancreaticoduodenectomy. 

“This shows us that sometimes we really do need to significantly increase the dose of pancreatic enzyme replacement therapy,” reported Domínguez Muñoz. 
 

Clear Direction on Where to Start

Comoderator Kasper Overbeek, MD, from the department of gastroenterology and hepatology, Erasmus MC Cancer Institute, University Medical Center, the Netherlands, commented: “It’s a useful study because it gives us practical advice on what to do in specific cases.”

Dr. Overbeek

Until now, we’ve done the same thing for everyone, he said, “but these data clearly show that this is not optimal.” 

In addition, “it is often the case with enzyme replacement therapy that doctors under-dose so it is necessary to increase the dose,” he said.

“This work gives us a clearer direction on where to start,” Overbeek said. “For example, with patients who have cancer, because they do not have time to start low and titrate up, they need a higher dose than patients with chronic pancreatitis.”

This pragmatic and novel guidance will “help us in our clinical practice,” he added.

Domínguez Muñoz reports receiving speaking and consultancy fees from Viatris, Abbott Pharmaceuticals, and Boston Scientific. Overbeek reports no relevant disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

SAVANNAH, GEORGIA — There’s no medical treatment for Charcot-Marie-Tooth (CMT) disease, a debilitating neurologic disorder that’s both progressive and incurable. But now, nerve specialists learned, new potential treatments are moving closer to clinical trials.

Genetic-based therapies for CMT are currently in preclinical research phases, and an experimental small-molecule drug has reached phase 3 in humans, neurologists told an audience at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024. But the neurologists also noted challenges, such as determining the best way to track disease progression — which can be slow — and the need to recruit high numbers of patients for trials.
 

A Common Genetic Neuromuscular Disorder

As Mario Saporta, MD, PhD, MBA, of the University of Miami, Coral Gables, Florida, explained, CMT is the most common genetic neuromuscular disorder, affecting 1 in 2500 people or about 130,000-150,000 in the United States. “Typically, it’s a length-dependent neuropathy, where your longest nerves would be affected earlier and more severely. That’s why we see foot deformities, inverted champagne bottle legs, and hand atrophy.”

Most patients with CMT in the United States have type 1A, which is linked to duplication of the PMP22 gene. All types lead to axonal degeneration, which appears to be the main cause of functional disability, Saporta said. “Patients become weaker and then progress with time, following the degree of axonal generation that they have.”

As many as 150 genes may eventually be deemed to cause CMT. The high number of genetically different forms makes diagnosis and genetic therapy difficult, he said, but that’s just part of the picture. Variations among mutations mean there’s “probably actually over 1000 different diseases” within CMT from a biologic perspective.
 

Genetic Therapy

In regard to genetic treatment, Bipasha Mukherjee-Clavin, MD, PhD, of Johns Hopkins University School of Medicine, Baltimore, Maryland, said a key factor is whether the patient’s form of CMT is passed on in an autosomal dominant or autosomal recessive manner.

“Autosomal dominant conditions are typically caused by gain of function mutations. So that means the goal of our genetic therapeutic would be to reduce expression of the mutated gene,” she said. “In contrast, autosomal recessive conditions are caused by loss-of-function mutations, which means the goal of our genetic therapeutic would be to replace the mutated gene with a normal, wild-type copy.”

A tool like CRISPR could be used to directly edit the part of the genome with a CMT-causing mutation or a viral vector could deliver a healthy, wild-type copy of a gene, she said. These approaches are both being tested.

Another approach is to reduce expression at the RNA level. “RNA therapeutics are FDA [Food and Drug Administration]–approved for other neuromuscular indications, and you may well be using some of these in your own clinical practice,” she said.

Currently, about seven different projects are in the works on the RNA therapeutics front in CMT, she said, including six focusing on type 1A. Mukherjee-Clavin believes that this subtype is a “great” target because it’s so common, affecting an estimated 1 in 5000 people.

“You actually have enough patients to power a clinical trial,” she said. Also, “it’s a homogeneous population, both in terms of the genetics and in terms of the clinical presentation.”
 

Preclinical Treatment Approaches

However, there are challenges. Drug delivery to Schwann cells, which insulate axons, is difficult, she said. “The other problem is that we want to avoid overly silencing PMP22 because that runs the theoretical risk of causing a different condition, HNPP [hereditary neuropathy with liability to pressure palsies]. HNPP is caused by deletions of PMP22, so we want to avoid that situation.”

Mukherjee-Clavin highlighted two RNA therapeutic products that she expects to move from preclinical to clinical research soon.

One is TVR110 by Armatus Bio, a microRNA intrathecal injection product, which aims to reduce PMP22 overexpression. “It targets basically reduces PMP22 mRNA expression and then normalizes the amount of PMP22 protein that is ultimately generated,” she said.

The other therapy, a small interfering RNA intravenous product delivered to Schwann cells, is being developed by DTx Pharma/Novartis.

Outside of the RNA arena, “there are a number of other programs that are in the preclinical phases that I think will be moving through this pipeline,” Mukherjee-Clavin said. “We’ll see if some of these enter first-in-human clinical trials.”

Meanwhile, Saporta highlighted small-molecule strategies that target a subtype of CMT called sorbitol dehydrogenase (SORD) deficiency that’s caused by mutations in the SORD gene. He noted that Applied Therapeutics is testing an investigational drug called govorestat (AT-007) in 56 patients in a double-blind, randomized, placebo-controlled phase 3 registrational study. The company recently reported that interim 12-month results are promising.

Saporta disclosed consulting for DTx Pharma/Novartis, Applied Therapeutics, and Pharnext. Mukherjee-Clavin had no disclosures.

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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

TOPLINE:

VIENNA — Individuals with ulcerative colitis (UC) who carry the HLA-DRB1*01:03 allele are at increased risk of having a more severe disease course requiring major surgery, hospitalization, and high-dose systemic corticosteroids within 3 years of diagnosis, according to a Danish study.

METHODOLOGY:

• Reliable biomarkers are lacking to identify patients with inflammatory bowel disease at greater risk for severe disease and who therefore might require intensified monitoring and treatment.
• Researchers explored genetic variants associated with severe UC in patients from two Danish cohorts, whose DNA was extracted from dried blood spots and full blood, with genotyping then performed to assess the presence of human leukocyte antigen (HLA) alleles and single-nucleotide variants.
• Severe UC was defined as having at least one major UC-related operation, at least two UC-related hospitalizations exceeding 2 days, and/or use of at least 5000 mg of systemic corticosteroids within 3 years of diagnosis. Patients not meeting these criteria were considered to have less severe UC and included as the comparison group.
• A genome-wide association study was conducted comparing severe vs less severe UC.

TAKEAWAY:

• Researchers analyzed 4491 patients with UC (mean age at diagnosis, 23 years; 53% women; 27% with severe UC) and determined that carriers of the HLA-DRB1*01:03 allele had a significantly higher risk for severe UC (odds ratio, 3.32).
• Compared with noncarriers, those with this allele had an approximately sixfold increased risk of needing major surgery, a fivefold increased risk of requiring at least two hospitalizations, and a twofold increased risk for use of over 5000 mg of systemic corticosteroids within 3 years of diagnosis.
• Time-to-event analysis showed that the association between carriers and disease severity extended beyond 3 years after diagnosis.
• Compared with noncarriers, those with the HLA-DRB1*01:03 allele had a higher hazard ratio for time to hospitalization, major surgery, and first treatment with systemic corticosteroids.

IN PRACTICE:

“Although HLA-DRB1*01:03 is a low-frequency allele, carriers have a significantly higher risk of severe ulcerative colitis. Given the low cost of typing a single HLA allele, HLA-DRB1*01:03 could be a valuable tool for risk assessment of patients with ulcerative colitis at diagnosis,” the authors concluded.

SOURCE:

The study, with first author Marie Vibeke Vestergaard, MSc, Aalborg University, Aalborg, Denmark, was published online on October 15 in JAMA, to coincide with its presentation at United European Gastroenterology (UEG) Week 2024 in Vienna, Austria. 

LIMITATIONS:

The findings are based on a Danish population of European genetic ancestry and require validation in diverse patient cohorts with UC.

DISCLOSURES:

The study was funded by the Danish National Research Foundation, the Lundbeck Foundation, and the Novo Nordisk Foundation. The authors reported no relevant disclosures related to the study.
 

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.

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.