A simple, flexible, and versatile way to ensure the AGA Research Foundation can continue our work for years to come is a gift in your will or living trust, known as a charitable bequest. To make a charitable bequest, you need a current will or living trust.

Your gift can be made as a percentage of your estate. Or you can make a specific bequest by giving a certain amount of cash, securities, or property. After your lifetime, the AGA Research Foundation receives your gift.

We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”

When planning a future gift, it’s sometimes difficult to determine what size donation will make sense. Emergencies happen, and you need to make sure your family is financially taken care of first. Including a bequest of a percentage of your estate ensures that your gift will remain proportionate no matter how your estate’s value fluctuates over the years.

Whether you would like to put your donation to work today or benefit us after your lifetime, you can find a charitable plan that lets you provide for your family and support the AGA Research Foundation.

Please contact us for more information at [email protected] or visit gastro.planmylegacy.org.

A simple, flexible, and versatile way to ensure the AGA Research Foundation can continue our work for years to come is a gift in your will or living trust, known as a charitable bequest. To make a charitable bequest, you need a current will or living trust.

Your gift can be made as a percentage of your estate. Or you can make a specific bequest by giving a certain amount of cash, securities, or property. After your lifetime, the AGA Research Foundation receives your gift.

We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”

When planning a future gift, it’s sometimes difficult to determine what size donation will make sense. Emergencies happen, and you need to make sure your family is financially taken care of first. Including a bequest of a percentage of your estate ensures that your gift will remain proportionate no matter how your estate’s value fluctuates over the years.

Whether you would like to put your donation to work today or benefit us after your lifetime, you can find a charitable plan that lets you provide for your family and support the AGA Research Foundation.

Please contact us for more information at [email protected] or visit gastro.planmylegacy.org.

A simple, flexible, and versatile way to ensure the AGA Research Foundation can continue our work for years to come is a gift in your will or living trust, known as a charitable bequest. To make a charitable bequest, you need a current will or living trust.

Your gift can be made as a percentage of your estate. Or you can make a specific bequest by giving a certain amount of cash, securities, or property. After your lifetime, the AGA Research Foundation receives your gift.

We hope you’ll consider including a gift to the AGA Research Foundation in your will or living trust. It’s simple – just a few sentences in your will or trust are all that is needed. The official bequest language for the AGA Research Foundation is: “I, [name], of [city, state, ZIP], give, devise, and bequeath to the AGA Research Foundation [written amount or percentage of the estate or description of property] for its unrestricted use and purpose.”

When planning a future gift, it’s sometimes difficult to determine what size donation will make sense. Emergencies happen, and you need to make sure your family is financially taken care of first. Including a bequest of a percentage of your estate ensures that your gift will remain proportionate no matter how your estate’s value fluctuates over the years.

Whether you would like to put your donation to work today or benefit us after your lifetime, you can find a charitable plan that lets you provide for your family and support the AGA Research Foundation.

Please contact us for more information at [email protected] or visit gastro.planmylegacy.org.

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Prescribing a biologic for people with Crohn’s disease is a complicated process that includes consideration of previous therapy, the severity of disease, cost, and other factors. Missing, however, has been the ability to accurately predict endoscopic response to a specific biologic agent to guide choice of therapy.

New peripheral blood biomarkers based on DNA methylation could soon help predict endoscopic response to adalimumab, vedolizumab, and ustekinumab for people with Crohn’s disease.

Although the biomarker panels are not yet clinically available, researchers demonstrated that they are accurate, valid, stable over time, and largely specific to each of the three biologic agents.

“Evidence over the last 10 years has shown a consistent difference in DNA methylation between people with IBD [inflammatory bowel disease] and healthy controls. Many of these studies suggest a role for DNA methylation for treatment response prediction,” Vincent Joustra, PhD, said when presenting results of the EPIC-CD trial at the annual congress of the European Crohn’s and Colitis Organisation.

After comparing endoscopic responders to nonresponders in different datasets. researchers found that “DNA methylation profiles are, in fact, associated with response to adalimumab, vedolizumab, and ustekinumab,” added Dr. Joustra, visiting fellow in the department of gastroenterology and hepatology at Amsterdam University Medical Centers.

DNA methylation – the presence or absence of a methyl group on a specific DNA location called a CpG – does not change a person’s genotype. Rather, the methylation process either activates or deactivates a gene’s expression. It can be used to predict treatment response.

Within the past 2 decades, “biologics have revolutionized care of IBD patients. Yet, despite their clinical efficacy, treatment choice is currently based on trial and error, which is suboptimal,” Dr. Joustra said.

Adding biomarkers to improve biologic medication selection is “urgently needed,” he added. “However, such biomarkers are not available for practice today.”
 

Methylation methodology

Dr. Joustra and colleagues prospectively studied DNA methylation in the peripheral blood samples of 184 adults with Crohn’s disease. They compared the biomarkers at baseline in people set to start biologic therapy and again at a median of 28 weeks following treatment with adalimumab (58 patients), vedolizumab (64 patients), and ustekinumab (62 patients).

Participants were divided into a discovery cohort to identify relevant biomarkers and a validation cohort to confirm the findings. Results were validated against a separate cohort of patients at Oxford (England) University.

Response was strictly defined as a decrease of at least 50% in a simple endoscopic score for Crohn’s disease, corticosteroid-free clinical response or remission using the Harvey Bradshaw Index, and/or biochemical response or remission.

Before patients were treated, the investigators created three epigenetic panels. The CpG loci of interest were identified using the Infinium MethylationEPIC BeadChip array, which measures over 850,000 CpG sites across the whole genome.

Key findings

One epigenetic panel featured 100 CpG loci relevant for adalimumab that correlated to an “endoscopic response with high accuracy,” with an area under the curve of 0.73 upon validation. A second panel, created for vedolizumab, included 22 CpG loci and had an AUC accuracy of 0.89. The third panel, specific to ustekinumab, had 68 CpG loci and an AUC accuracy of 0.94.

The markers are largely unique to each agent. Only two CpG loci overlapped between adalimumab and ustekinumab, Dr. Joustra said.

“Importantly, our model was able to predict response prior to treatment in a completely different set of patients from the Oxford validation cohort with an AUC of 0.75,” Dr. Joustra said.

A secondary analysis revealed no differences in the stability and robustness of the methylation markers between baseline and 28 weeks. This finding implies that the biomarkers are stable during the induction and maintenance phases of treatment.

“Of course, we need to clinically validate our findings in a clinical trial, which is ongoing,” Dr. Joustra said. This work will continue in the EPIC-CD study, as well as in the OMICROHN clinical trial.
 

Promising start

“These are really interesting findings that address an area of importance in treating patients with Crohn’s disease,” said ECCO session comoderator Tim Raine, PhD, who was not affiliated with the research.

“The team found a signature that appears to provide helpful prediction of response to specific treatments. Importantly, this signature appeared to be stable over time, to be specific to individual drugs, and could be validated in an external cohort of patients,” added Dr. Raine, consultant gastroenterologist at Cambridge (England) University Hospitals NHS Trust.

Although the technologies used in EPIC-CD are not yet routinely available in clinical practice, “the methodologies are well established, and with appropriate development in a validated laboratory, as well as further validation work, could form a useful test for gastroenterologists treating patients with Crohn’s disease,” Dr. Raine said.

The study was independently supported. Dr. Joustra and Dr. Raine reported no relevant financial relationships.

Help your patients understand biologics and biosimilars by using AGA resources for providers and patients available at gastro.org/biosimilars. 

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

Pulmonary function was significantly associated with frailty in community-dwelling older adults over a 5-year period, as indicated by data from more than 1,000 individuals.

The pulmonary function test has been proposed as a predictive tool for clinical outcomes in geriatrics, including hospitalization, mortality, and frailty, but data on the relationship between pulmonary function and frailty in community-dwelling adults are limited and inconsistent, write Walter Sepulveda-Loyola, MD, of Universidad de Las Americas, Santiago, Chile, and colleagues.

In an observational study published in Heart and Lung, the researchers reviewed data from adults older than 64 years who were participants in the Toledo Study for Healthy Aging.

The study population included 1,188 older adults (mean age, 74 years; 54% women). The prevalence of frailty at baseline ranged from 7% to 26%.

Frailty was defined using the frailty phenotype (FP) and the Frailty Trait Scale 5 (FTS5). Pulmonary function was determined on the basis of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), using spirometry.

Overall, at the 5-year follow-up, FEV1 and FVC were inversely associated with prevalence and incidence of frailty in nonadjusted and adjusted models using FP and FTS5.

In adjusted models, FEV1 and FVC, as well as FEV1 and FVC percent predicted value, were significantly associated with the prevalence of frailty, with odds ratios ranging from 0.53 to 0.99. FEV1 and FVC were significantly associated with increased incidence of frailty, with odds ratios ranging from 0.49 to 0.50 (P < .05 for both).

Pulmonary function also was associated with prevalent and incident frailty, hospitalization, and mortality in regression models, including the whole sample and after respiratory diseases were excluded.

Pulmonary function measures below the cutoff points for FEV1 and FVC were significantly associated with frailty, as well as with hospitalization and mortality. The cutoff points for FEV1 were 1.805 L for men and 1.165 L for women; cutoff points for FVC were 2.385 L for men and 1.585 L for women.

“Pulmonary function should be evaluated not only in frail patients, with the aim of detecting patients with poor prognoses regardless of their comorbidity, but also in individuals who are not frail but have an increased risk of developing frailty, as well as other adverse events,” the researchers write.

The study findings were limited by lack of data on pulmonary function variables outside of spirometry and by the need for data from populations with different characteristics to assess whether the same cutoff points are predictive of frailty, the researchers note.

The results were strengthened by the large sample size and additional analysis that excluded other respiratory diseases. Future research should consider adding pulmonary function assessment to the frailty model, the authors write.

Given the relationship between pulmonary function and physical capacity, the current study supports more frequent evaluation of pulmonary function in clinical practice for older adults, including those with no pulmonary disease, they conclude.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, financed by the European Regional Development Funds, and the Centro de Investigacion Biomedica en Red en Fragilidad y Envejecimiento Saludable and the Fundacion Francisco Soria Melguizo. Lead author Dr. Sepulveda-Loyola was supported by the Brazilian National Council for Scientific and Technological Development.

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

Pulmonary function was significantly associated with frailty in community-dwelling older adults over a 5-year period, as indicated by data from more than 1,000 individuals.

The pulmonary function test has been proposed as a predictive tool for clinical outcomes in geriatrics, including hospitalization, mortality, and frailty, but data on the relationship between pulmonary function and frailty in community-dwelling adults are limited and inconsistent, write Walter Sepulveda-Loyola, MD, of Universidad de Las Americas, Santiago, Chile, and colleagues.

In an observational study published in Heart and Lung, the researchers reviewed data from adults older than 64 years who were participants in the Toledo Study for Healthy Aging.

The study population included 1,188 older adults (mean age, 74 years; 54% women). The prevalence of frailty at baseline ranged from 7% to 26%.

Frailty was defined using the frailty phenotype (FP) and the Frailty Trait Scale 5 (FTS5). Pulmonary function was determined on the basis of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), using spirometry.

Overall, at the 5-year follow-up, FEV1 and FVC were inversely associated with prevalence and incidence of frailty in nonadjusted and adjusted models using FP and FTS5.

In adjusted models, FEV1 and FVC, as well as FEV1 and FVC percent predicted value, were significantly associated with the prevalence of frailty, with odds ratios ranging from 0.53 to 0.99. FEV1 and FVC were significantly associated with increased incidence of frailty, with odds ratios ranging from 0.49 to 0.50 (P < .05 for both).

Pulmonary function also was associated with prevalent and incident frailty, hospitalization, and mortality in regression models, including the whole sample and after respiratory diseases were excluded.

Pulmonary function measures below the cutoff points for FEV1 and FVC were significantly associated with frailty, as well as with hospitalization and mortality. The cutoff points for FEV1 were 1.805 L for men and 1.165 L for women; cutoff points for FVC were 2.385 L for men and 1.585 L for women.

“Pulmonary function should be evaluated not only in frail patients, with the aim of detecting patients with poor prognoses regardless of their comorbidity, but also in individuals who are not frail but have an increased risk of developing frailty, as well as other adverse events,” the researchers write.

The study findings were limited by lack of data on pulmonary function variables outside of spirometry and by the need for data from populations with different characteristics to assess whether the same cutoff points are predictive of frailty, the researchers note.

The results were strengthened by the large sample size and additional analysis that excluded other respiratory diseases. Future research should consider adding pulmonary function assessment to the frailty model, the authors write.

Given the relationship between pulmonary function and physical capacity, the current study supports more frequent evaluation of pulmonary function in clinical practice for older adults, including those with no pulmonary disease, they conclude.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, financed by the European Regional Development Funds, and the Centro de Investigacion Biomedica en Red en Fragilidad y Envejecimiento Saludable and the Fundacion Francisco Soria Melguizo. Lead author Dr. Sepulveda-Loyola was supported by the Brazilian National Council for Scientific and Technological Development.

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

Pulmonary function was significantly associated with frailty in community-dwelling older adults over a 5-year period, as indicated by data from more than 1,000 individuals.

The pulmonary function test has been proposed as a predictive tool for clinical outcomes in geriatrics, including hospitalization, mortality, and frailty, but data on the relationship between pulmonary function and frailty in community-dwelling adults are limited and inconsistent, write Walter Sepulveda-Loyola, MD, of Universidad de Las Americas, Santiago, Chile, and colleagues.

In an observational study published in Heart and Lung, the researchers reviewed data from adults older than 64 years who were participants in the Toledo Study for Healthy Aging.

The study population included 1,188 older adults (mean age, 74 years; 54% women). The prevalence of frailty at baseline ranged from 7% to 26%.

Frailty was defined using the frailty phenotype (FP) and the Frailty Trait Scale 5 (FTS5). Pulmonary function was determined on the basis of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), using spirometry.

Overall, at the 5-year follow-up, FEV1 and FVC were inversely associated with prevalence and incidence of frailty in nonadjusted and adjusted models using FP and FTS5.

In adjusted models, FEV1 and FVC, as well as FEV1 and FVC percent predicted value, were significantly associated with the prevalence of frailty, with odds ratios ranging from 0.53 to 0.99. FEV1 and FVC were significantly associated with increased incidence of frailty, with odds ratios ranging from 0.49 to 0.50 (P < .05 for both).

Pulmonary function also was associated with prevalent and incident frailty, hospitalization, and mortality in regression models, including the whole sample and after respiratory diseases were excluded.

Pulmonary function measures below the cutoff points for FEV1 and FVC were significantly associated with frailty, as well as with hospitalization and mortality. The cutoff points for FEV1 were 1.805 L for men and 1.165 L for women; cutoff points for FVC were 2.385 L for men and 1.585 L for women.

“Pulmonary function should be evaluated not only in frail patients, with the aim of detecting patients with poor prognoses regardless of their comorbidity, but also in individuals who are not frail but have an increased risk of developing frailty, as well as other adverse events,” the researchers write.

The study findings were limited by lack of data on pulmonary function variables outside of spirometry and by the need for data from populations with different characteristics to assess whether the same cutoff points are predictive of frailty, the researchers note.

The results were strengthened by the large sample size and additional analysis that excluded other respiratory diseases. Future research should consider adding pulmonary function assessment to the frailty model, the authors write.

Given the relationship between pulmonary function and physical capacity, the current study supports more frequent evaluation of pulmonary function in clinical practice for older adults, including those with no pulmonary disease, they conclude.

The study was supported by the Spanish Ministry of Economy, Industry, and Competitiveness, financed by the European Regional Development Funds, and the Centro de Investigacion Biomedica en Red en Fragilidad y Envejecimiento Saludable and the Fundacion Francisco Soria Melguizo. Lead author Dr. Sepulveda-Loyola was supported by the Brazilian National Council for Scientific and Technological Development.

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

The Food and Drug Administration has accepted a new drug application for berdazimer gel 10.3% for the treatment of molluscum contagiosum, the manufacturer announced on March 7.

If approved, berdazimer gel would be the first FDA-approved prescription product for molluscum contagiosum in the United States, according to the company, Novan. The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a novel nitric oxide–releasing agent.

Molluscum contagiosum is a benign but contagious skin infection characterized by red papules on the face, trunk, limbs, and axillae that may persist for years if left untreated.

The treatment was evaluated in the B-SIMPLE4 study, a phase 3 clinical trial including 891 individuals with molluscum contagiosum aged 6 months and older, with 3-70 raised lesions The mean age of the patients was approximately 7 years (range, 0.9-47.5 years) and 85.5% were White (4.7% were Black, 21.2% were Hispanic, and 1.4% were Asian). Study participants were randomized to berdazimer gel 10.3% or a vehicle gel applied as a thin layer to all lesions once daily for 12 weeks.

The full results of the B-SIMPLE4 study were published in JAMA Dermatology in July 2022. After 12 weeks of treatment, 32.4% of patients in the berdazimer group met the primary outcome of complete clearance of all lesions, versus 19.7% of those on the vehicle (P < .001). The rates of adverse events were similar and low in both groups. The most common adverse events in both groups were application-site pain and erythema, and most cases were mild or moderate. A total of 4.1% of berdazimer patients and 0.7% of placebo patients experienced adverse events that prompted treatment discontinuation.

The Prescription Drug User Fee goal date for the approval of berdazimer 10.3% for molluscum contagiosum is set for Jan. 5, 2024, according to Novan.

The Food and Drug Administration has accepted a new drug application for berdazimer gel 10.3% for the treatment of molluscum contagiosum, the manufacturer announced on March 7.

If approved, berdazimer gel would be the first FDA-approved prescription product for molluscum contagiosum in the United States, according to the company, Novan. The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a novel nitric oxide–releasing agent.

Molluscum contagiosum is a benign but contagious skin infection characterized by red papules on the face, trunk, limbs, and axillae that may persist for years if left untreated.

The treatment was evaluated in the B-SIMPLE4 study, a phase 3 clinical trial including 891 individuals with molluscum contagiosum aged 6 months and older, with 3-70 raised lesions The mean age of the patients was approximately 7 years (range, 0.9-47.5 years) and 85.5% were White (4.7% were Black, 21.2% were Hispanic, and 1.4% were Asian). Study participants were randomized to berdazimer gel 10.3% or a vehicle gel applied as a thin layer to all lesions once daily for 12 weeks.

The full results of the B-SIMPLE4 study were published in JAMA Dermatology in July 2022. After 12 weeks of treatment, 32.4% of patients in the berdazimer group met the primary outcome of complete clearance of all lesions, versus 19.7% of those on the vehicle (P < .001). The rates of adverse events were similar and low in both groups. The most common adverse events in both groups were application-site pain and erythema, and most cases were mild or moderate. A total of 4.1% of berdazimer patients and 0.7% of placebo patients experienced adverse events that prompted treatment discontinuation.

The Prescription Drug User Fee goal date for the approval of berdazimer 10.3% for molluscum contagiosum is set for Jan. 5, 2024, according to Novan.

The Food and Drug Administration has accepted a new drug application for berdazimer gel 10.3% for the treatment of molluscum contagiosum, the manufacturer announced on March 7.

If approved, berdazimer gel would be the first FDA-approved prescription product for molluscum contagiosum in the United States, according to the company, Novan. The active ingredient in berdazimer gel 10.3% is berdazimer sodium, a novel nitric oxide–releasing agent.

Molluscum contagiosum is a benign but contagious skin infection characterized by red papules on the face, trunk, limbs, and axillae that may persist for years if left untreated.

The treatment was evaluated in the B-SIMPLE4 study, a phase 3 clinical trial including 891 individuals with molluscum contagiosum aged 6 months and older, with 3-70 raised lesions The mean age of the patients was approximately 7 years (range, 0.9-47.5 years) and 85.5% were White (4.7% were Black, 21.2% were Hispanic, and 1.4% were Asian). Study participants were randomized to berdazimer gel 10.3% or a vehicle gel applied as a thin layer to all lesions once daily for 12 weeks.

The full results of the B-SIMPLE4 study were published in JAMA Dermatology in July 2022. After 12 weeks of treatment, 32.4% of patients in the berdazimer group met the primary outcome of complete clearance of all lesions, versus 19.7% of those on the vehicle (P < .001). The rates of adverse events were similar and low in both groups. The most common adverse events in both groups were application-site pain and erythema, and most cases were mild or moderate. A total of 4.1% of berdazimer patients and 0.7% of placebo patients experienced adverse events that prompted treatment discontinuation.

The Prescription Drug User Fee goal date for the approval of berdazimer 10.3% for molluscum contagiosum is set for Jan. 5, 2024, according to Novan.

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Children who suffer from persistent bad dreams may be at increased risk for cognitive impairment or Parkinson’s disease (PD) later in life, new research shows.

Compared with children who never had distressing dreams between ages 7 and 11 years, those who had persistent distressing dreams were 76% more likely to develop cognitive impairment and roughly seven times more likely to develop PD by age 50 years.

It’s been shown previously that sleep problems in adulthood, including distressing dreams, can precede the onset of neurodegenerative diseases such as Alzheimer’s disease (AD) or PD by several years, and in some cases decades, study investigator Abidemi Otaiku, BMBS, University of Birmingham (England), told this news organization.

However, no studies have investigated whether distressing dreams during childhood might also be associated with increased risk for cognitive decline or PD.

“As such, these findings provide evidence for the first time that certain sleep problems in childhood (having regular distressing dreams) could be an early indicator of increased dementia and PD risk,” Dr. Otaiku said.

He noted that the findings build on previous studies which showed that regular nightmares in childhood could be an early indicator for psychiatric problems in adolescence, such as borderline personality disorder, attention-deficit/hyperactivity disorder, and psychosis.

The study was published online February 26 in The Lancet journal eClinicalMedicine.

Statistically significant

The prospective, longitudinal analysis used data from the 1958 British Birth Cohort Study, a prospective birth cohort which included all people born in Britain during a single week in 1958.

At age 7 years (in 1965) and 11 years (in 1969), mothers were asked to report whether their child experienced “bad dreams or night terrors” in the past 3 months, and cognitive impairment and PD were determined at age 50 (2008).

Among a total of 6,991 children (51% girls), 78.2% never had distressing dreams, 17.9% had transient distressing dreams (either at ages 7 or 11 years), and 3.8% had persistent distressing dreams (at both ages 7 and 11 years).

By age 50, 262 participants had developed cognitive impairment, and five had been diagnosed with PD.

After adjusting for all covariates, having more regular distressing dreams during childhood was “linearly and statistically significantly” associated with higher risk of developing cognitive impairment or PD by age 50 years (P = .037). This was the case in both boys and girls.

Compared with children who never had bad dreams, peers who had persistent distressing dreams (at ages 7 and 11 years) had an 85% increased risk for cognitive impairment or PD by age 50 (adjusted odds ratio, 1.85; 95% confidence interval, 1.10-3.11; P = .019).

The associations remained when incident cognitive impairment and incident PD were analyzed separately.

Compared with children who never had distressing dreams, children who had persistent distressing dreams were 76% more likely to develop cognitive impairment by age 50 years (aOR, 1.76; 95% CI, 1.03-2.99; P = .037), and were about seven times more likely to be diagnosed with PD by age 50 years (aOR, 7.35; 95% CI, 1.03-52.73; P = .047).

The linear association was statistically significant for PD (P = .050) and had a trend toward statistical significance for cognitive impairment (P = .074).

Mechanism unclear

“Early-life nightmares might be causally associated with cognitive impairment and PD, noncausally associated with cognitive impairment and PD, or both. At this stage it remains unclear which of the three options is correct. Therefore, further research on mechanisms is needed,” Dr. Otaiku told this news organization.

“One plausible noncausal explanation is that there are shared genetic factors which predispose individuals to having frequent nightmares in childhood, and to developing neurodegenerative diseases such as AD or PD in adulthood,” he added.

It’s also plausible that having regular nightmares throughout childhood could be a causal risk factor for cognitive impairment and PD by causing chronic sleep disruption, he noted.

“Chronic sleep disruption due to nightmares might lead to impaired glymphatic clearance during sleep – and thus greater accumulation of pathological proteins in the brain, such as amyloid-beta and alpha-synuclein,” Dr. Otaiku said.

Disrupted sleep throughout childhood might also impair normal brain development, which could make children’s brains less resilient to neuropathologic damage, he said.

Clinical implications?

There are established treatments for childhood nightmares, including nonpharmacologic approaches.

“For children who have regular nightmares that lead to impaired daytime functioning, it may well be a good idea for them to see a sleep physician to discuss whether treatment may be needed,” Dr. Otaiku said.

But should doctors treat children with persistent nightmares for the purpose of preventing neurodegenerative diseases in adulthood or psychiatric problems in adolescence?

“It’s an interesting possibility. However, more research is needed to confirm these epidemiological associations and to determine whether or not nightmares are a causal risk factor for these conditions,” Dr. Otaiku concluded.

The study received no external funding. Dr. Otaiku reports no relevant disclosures.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not. The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Patients with celiac disease who have COVID-19 are twice as likely to be hospitalized as are individuals without the autoimmune condition, a single-center U.S. study shows.

Vaccination against COVID-19 reduced the risk for hospitalization by almost half for both groups, however, the study finds.

“To our knowledge this is the first study that demonstrated a vaccination effect on mitigation of the risk of hospitalization in celiac disease patients with COVID-19 infection,” write Alberto Rubio-Tapia, MD, director, Celiac Disease Program, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, and colleagues.

Despite the increased risk for hospitalization among patients with celiac disease, there were no significant differences between those with and without the condition with respect to intensive care unit requirement, mortality, or thrombosis, the researchers found.

The findings suggest that celiac disease patients with COVID-19 are “not inherently at greater risk for more severe outcomes,” they wrote.

The study was published online in Clinical Gastroenterology and Hepatology.
 

Comparing outcomes

Although it has been shown that patients with celiac disease have increased susceptibility to viral illnesses, research to date has found similar COVID-19 incidence and outcomes, including hospitalization, between patients with celiac disease and the general population, the researchers wrote.

However, the impact of COVID-19 vaccination is less clear, so the researchers set out to compare the frequency of COVID-19–related outcomes between patients with and without celiac disease before and after vaccination.

Through an analysis of patient medical records, researchers found 171,763 patients diagnosed and treated for COVID-19 at their institution between March 1, 2020, and Jan 1, 2022. Of them, 110 adults had biopsy-proven celiac disease.

The median time from biopsy diagnosis of celiac disease to COVID-19 was 217 months, 66.3% of patients were documented to be following a gluten-free diet, and tissue transglutaminase IgA was positive in 46.2% at the time of COVID-19.

The celiac group was matched by age, ethnicity, sex, and date of COVID-19 diagnosis with a control group of 220 adults without a clinical diagnosis of celiac disease. The two cohorts had similar rates of comorbid obesity, type 2 diabetes, preexisting lung disease, and tobacco use.

Patients with celiac disease were significantly more likely to be hospitalized for COVID-19 than were the control participants, at 24% vs. 11% (hazard ratio, 2.1; P = .009), the researchers wrote.

However, hospitalized patients with celiac disease were less likely to require supplementary oxygen than were the control participants, at 63% vs. 84%.

Vaccination rates for COVID-19 were similar between the two groups, at 64.5% among patients with celiac disease and 70% in the control group. Vaccination was associated with a lower risk for hospitalization on multivariate analysis (HR, 0.53; P = .026).

There was no significant difference in hospitalization rates between vaccinated patients with celiac disease and vaccinated patients in the control group (odds ratio, 1.12; P = .79), the team reported.

The secondary outcomes of ICU requirement, mortality, and thrombosis were minimal in both groups, the researchers wrote.

Vaccination’s importance

The different findings regarding hospitalization risk among patients with celiac disease between this study and previous research are likely due to earlier studies not accounting for vaccination status, the researchers wrote.

“This study shows significantly different rates of hospitalization among patients with [celiac disease] depending on their vaccination status, with strong evidence for mitigation of hospitalization risk through vaccination,” they added.

“Vaccination against COVID-19 should be strongly recommended in patients with celiac disease,” the researchers concluded.

No funding was declared. Dr. Rubio-Tapia reported a relationship with Takeda. No other financial relationships were declared.

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

AGA offers guidance on celiac disease to help patients maintain a gluten-free diet in the AGA GI Patient Center: www.gastro.org/celiac .

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Following a fish-based pescatarian diet or plant-based vegetarian or vegan diet is associated with not only the greatest benefit to health but also the lowest impact on the environment, suggests a new analysis that reveals meat-based, as well as keto and paleo diets, to be the worst on both measures.

The research was published online in The American Journal of Clinical Nutrition.

To obtain a real-world view on the environmental and health impact of diets as consumed by U.S. adults, the team examined a nationally representative survey of the 1-day eating habits of more than 16,000 individuals.

This revealed that the best quality diet was pescatarian, followed by vegetarian and vegan diets. Omnivore diets, although less healthy, tended to score better than keto and paleo diets, which were the lowest ranked.

Both keto and paleo diets tend to be higher in animal foods and lower in plant foods than other popular diets, the researchers explain in their study, and they both have been associated with negative effects on blood lipids, specifically increased LDL cholesterol, raising concern about the long-term health outcomes associated with these diets.”

Analysis of the environmental impact of the different eating patterns showed that the vegan diet had the lowest carbon footprint, followed by the vegetarian and pescatarian diets. The omnivore, paleo, and keto diets had a far higher carbon footprint, with that of the keto diet more than four times greater than that for a vegan diet.

“Climate change is arguably one of the most pressing problems of our time, and a lot of people are interested in moving to a plant-based diet,” said senior author Diego Rose, PhD, MPH, RD, in a press release.

“Based on our results, that would reduce your footprint and be generally healthy,” noted Dr. Rose, nutrition program director, Tulane University, New Orleans.

To determine the carbon footprint and quality of popular diets as they are consumed by U.S. adults, Keelia O’Malley, PhD, MPH, Amelia Willits-Smith, PhD, MSc, and Dr. Rose, all with Tulane University, studied 24-hour recall data from the ongoing, nationally representative National Health and Nutrition Examination Survey (NHANES) for the years 2005-2010.

The data, which was captured by trained interviewers using a validated tool, was matched with the U.S. Department of Agriculture Food Patterns Equivalents Database to categorize the participants into one of six mutually exclusive categories: vegan, vegetarian, pescatarian, keto, paleo, or omnivore.

The omnivore category included anyone who did not fit into any of the preceding categories.

The environmental impact of the diets was then calculated by matching the established greenhouse gas emissions (GHGE) of over 300 commodities to foods listed on the NHANES, which was then summarized for each individual to give a carbon footprint for their 1-day diet.

Finally, the quality of their diet was estimated using the 2010 versions of the Healthy Eating Index and the Alternate Healthy Eating Index, both of which award a score to food components based on their impact on health.

Overall, 16,412 individuals were included in the analysis, of whom 52.1% were female.

The most common diet was omnivore, which was followed by 83.6% of respondents, followed by vegetarian (7.5%), pescatarian (4.7%), vegan (0.7%), keto (0.4%), and paleo diets (0.3%).

The lowest carbon footprint was seen with a vegan diet, at an average of 0.69 kg of carbon dioxide equivalents per 1,000 kcal consumed, followed by a vegetarian diet (1.16 kg of carbon dioxide equivalents per 1,000 kcal) and pescatarian diet (1.66 kg of carbon dioxide equivalents per 1,000 kcal).

The highest carbon footprints were observed with the omnivore (2.23 kg of carbon dioxide equivalents per 1,000 kcal), paleo (2.62 kg of carbon dioxide equivalents per 1,000 kcal), and keto diets (2.91 kg of carbon dioxide equivalents per 1,000 kcal).

In terms of diet quality, the pescatarian diet was ranked the highest on both eating index scores, followed by the vegetarian, then vegan, diets. The order of the three lowest scores depended on the index used, with either the keto or paleo diet deemed to be the worst quality.

Analysis of individuals following an omnivore diet suggested that those who ate in line with the DASH or Mediterranean diets had higher diet quality, as well as a lower environmental impact, than other people within the group.

Hence, Dr. Rose observed, “Our research ... shows there is a way to improve your health and footprint without giving up meat entirely.”

The researchers acknowledge that the use of 1-day diets has limitations, including that whatever individuals may have eaten during those 24 hours may not correspond to their overall day-in, day-out diet.

The study was supported by the Wellcome Trust. Dr. Rose declares relationships with the Center for Biological Diversity, the NCI, and the Health Resources and Services Administration. Dr. Willits-Smith has received funding from CBD and NCI. Dr. O’Malley has received funding from HRSA.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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

Drinking a no-or low-calorie nonnutritive sweetened (NNS) beverage was no different from drinking water in terms of effect on 2-hour postprandial levels of glucose and hormones related to appetite or food intake.

Drinking a sugar-sweetened beverage (SSB), however, had a different effect on postprandial levels of glucose and the hormones insulin, glucagonlike peptide–1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon.

These findings are from a new meta-analysis by Roselyn Zhang and colleagues, supported by the nonprofit organization Institute for the Advancement of Food and Nutrition Sciences. The study was published recently in Nutrients.

“Nonnutritive sweeteners have no acute metabolic or endocrine effects and they are similar to water in that respect, and they show a different response from caloric sweeteners,” study author Tauseef Khan, MBBS, PhD, summarized in an interview following a press briefing from the IAFNS.

“Our study supports that nonnutritive sweeteners are a healthier alternative to sugar-sweetened beverages or caloric beverages,” said Dr. Khan, an epidemiologist in the department of nutritional sciences, University of Toronto.

Most participants in the 36 trials included in the meta-analysis were healthy, he noted. However, for certain types of NNS beverages, “we had enough studies for type 2 diabetes to also assess that separately, and the results were the same: Nonnutritive sweeteners were no different from water; however, they were different from caloric sweeteners.”

Of note, none of the studies included erythritol – a sugar alcohol (polyol) increasingly used as an artificial sweetener in keto and other types of foods – which was associated with a risk for adverse cardiac events in a paper in Nature Medicine.
 

Are these NNS drinks largely inert?

“This [meta-analysis] implies that sweeteners are largely inert,” in terms of acute postprandial glucose and hormone response, but the review did not include newer reports that differ, Duane Mellor, PhD, RD, RNutr, who was not involved with the research, noted in an email.

“This is possibly,” he said, because the study “only reviewed the literature up until January 2022 and therefore it missed the World Health Organization review ‘Health Effects of the Use of Non-Sugar Sweeteners’ published in April [2022], and a study published in August 2022 in the journal Cell suggesting that some nonnutritive sweeteners may have a minor effect on gut microbiome and glucose response.

“Although there is a place of nonnutritive sweeteners as a way to reduce sugar intake, they are a small part of dietary pattern and lifestyle which can help reduce risk of disease,” said Dr. Mellor, a registered dietitian and senior teaching fellow at Aston University, Birmingham, England.

“So, although we are clear we need to reduce our intake of sugar-sweetened beverages, switching to non-nutritive sweetened beverages (such as diet sodas) is not necessarily the healthiest option, as unlike water, it seems that some nonnutritive sweeteners may influence glucose responses and levels of related hormones in more recent studies.”
 

NNS beverages ‘are similar to water’

Dr. Khan pointed out that the meta-analysis addressed two major concerns about NNS beverages.

First, the “sweet uncoupling hypothesis” proposes that low-calorie sweeteners affect sweet taste by separating sweet taste from calories. “The body is confused, and then there is hormonal change. Our study shows that actually that’s not true, and [NNS beverages] are similar to water.”

Second, when no-calorie or low-calorie sweeteners are taken with calories (coupling), a concern is that “then you eat more somehow, or your response is different. However, the results [in this meta-analysis] also show that that is not the case for glucose response, insulin response, and other hormonal markers.”

“The strength is not that low-calorie sweeteners have some benefit per se,” he elaborated. “The advantage is that they replace caloric beverages.

“We are not saying that anybody who is not taking low-calorie sweeteners should start taking [them],” he continued. “What we are saying is somebody who is taking sugar-sweetened beverages and has a problem of taking excess calories, if you replace those calories with low-calorie sweetener, replacement of calories itself may be beneficial, and also they should not be concerned of any [acute] issues with a moderate amount of low-calorie sweeteners.”
 

Postprandial effect of NNS beverages, SSBs, water

Eight NNS are currently approved by the Food and Drug Administration: aspartame, acesulfame potassium (ace-K), luo han guo (monkfruit) extract, neotame, saccharin, stevia, sucralose, and advantame, the researchers noted.

Ms. Zhang and colleagues searched the literature up until Jan. 15, 2022, for studies of NNS beverages and acute postprandial glycemic and endocrine responses.

Trials were excluded if they involved sugar alcohols (eg, erythritol) or rare sugars (eg, allulose), or if they were shorter than 2 hours, lacked a comparator arm, or did not provide suitable endpoint data.

They identified 36 randomized and nonrandomized clinical trials of 472 predominantly healthy participants: 21 trials (15 reports, n = 266) with NNS consumed alone (uncoupled), 3 trials (3 reports, n = 27) with NNS consumed in a solution containing a carbohydrate (coupled), and 12 trials (7 reports, n = 179) with NNS consumed up to 15 minutes before oral glucose carbohydrate load (delayed coupling).

The four types of beverages were single NNS (ace-K, aspartame, cyclamate, saccharin, stevia, and sucralose), NNS blends (ace-K + aspartame; ace-K + sucralose; ace-K + aspartame + cyclamate; and ace-K + aspartame + sucralose), SSBs (glucose, sucrose, and fructose), and water (control).

In the uncoupled interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon, with responses similar to water.

In the uncoupled interventions, SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses, with no differences in postprandial ghrelin and glucagon responses.

In the coupled and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects, with responses similar to water.

The studies generally had low to moderate confidence.

The study was supported by an unrestricted grant from IAFNS. Dr. Khan has received research support from the Canadian Institutes of Health Research, the International Life Sciences Institute, and the National Honey Board. He has received honorariums for lectures from the International Food Information Council and the IAFNS. Dr. Mellor has no disclosures.

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