A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

A large UK-based study has found that females, sexual minorities, and people experiencing socioeconomic disadvantage are most at-risk of “internalised” weight stigma, along with people who experienced family and media pressure to lose weight in childhood. This can continue to be the case as long as two decades after the childhood experiences.

“Internalised weight stigma” happens when a person adopts negative obesity-related stereotypes, such as thinking they are less attractive, less competent, or less valuable as a person due to their weight, even in situations where their BMI suggests such a view is not valid.

Researchers at the universities of Bristol and Leeds, with colleagues at institutions interested in weight and mental health issues, analyzed the link between internalised weight stigma in adulthood and adolescent experiences and social circumstances. Their work used data obtained as part of Bristol University’s ongoing Children of the 90s project. This recruited thousands of pregnant women between 1990 and 1991, and has now followed the health of them and their families for more than 30 years.

The investigation, published in The Lancet Regional Health, examined differences in internalised weight stigma in more than 4000 people aged 31 years, focusing on effects of sex, ethnicity, socioeconomic factors, sexual orientation, and family and wider social influences in childhood and adolescence. The data were obtained from responses to 11 targeted questions included within the more general questionnaire completed by Children of the 90s participants when aged 31.
 

Effects Unrelated to Weight

Social epidemiologist Amanda Hughes, BSc, MSc, PhD, at the MRC Epidemiology Unit in Bristol Medical School, first author of the research report, said that the study “was not about what weight you think you are, but about how that relates to your view of yourself as a human being.” She explained that the research identified factors that led to higher levels of long-term internalised weight stigma in adults two decades after negative experiences in childhood or youth, “regardless of what their actual weight was.” Even people in the acceptable BMI range had levels of internalised weight stigma that were associated with experiences around two decades earlier.

The headline finding of the study was that those most at risk of developing internalised weight stigma were females, sexual minorities, and people experiencing socioeconomic disadvantage. People who as teenagers felt pressure to lose weight from family, wider social interactions, or the media were also at elevated risk.

“There are definitely inequalities in who was affected by this psychologically,” Dr. Hughes said, and the inequalities were associated with the sex, nonheterosexuality, or socioeconomic circumstances, rather than being explained by differences in BMI. The differences in the psychological impact of negative early-life weight-related experiences, such as pressure from family, teasing, bullying, and general weight-shaming, showed up even among people of the same weight.

Dr. Hughes emphasized that the new value of this research comes from its sample size, the general spread of people sampled, and the long length of time over which the relationships between experiences and effects were analyzed. Previous evidence, globally, has come from small and nonrepresentative samples, such as psychology undergraduates or people engaged in weight management programs.

Rebecca Puhl, PhD, professor of human development and family sciences at Connecticut University, an internationally prominent researcher of internalized weight stigma issues, said: “This study adds new insights to the increasing evidence on internalised weight bias. Their findings that internalised weight bias is elevated among individuals with sexual minority identities and those with socioeconomically disadvantaged backgrounds highlight the importance of addressing weight stigma and its consequences among populations with multiple stigmatised identities.” She added that the findings “reiterate the need for far-reaching stigma reduction interventions.” Dr. Puhl was not involved in this study.
 

Promote Healthy, Not Thin

Dr. Hughes stressed that interventions to address the issue, by efforts to change attitudes in family life, the media, and other approaches, should continue to promote healthy weight management amongst youngsters, while avoiding the dangers of inappropriate stigma and the resulting mental health problems.

“The crucial thing is … don’t frame [nutritional guidance] in terms of: if you do these things you’ll be thinner and thinner is better,” Dr. Hughes said. She stressed that the most important approach is to promote good nutrition for health, without making it all about being thin.

Dr. Hughes said there are many further things the researchers would like to do to take their work forward, including getting a more detailed look at the psychological processes involved and the relationship between internalised weight stigma and other aspects of mental health.

Dr. Hughes has no relevant interests to disclose. Dr. Puhl has no relevant interests to disclose, but is currently receiving funding from Eli Lilly.

A version of this article appeared on Medscape.com.

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.

On the heels of the January 2024 announcement by GlaxoSmithKline that its Flovent inhalers are being discontinued, Teva’s recent announcement that it will discontinue U.S. distribution of its Digihaler^® products is adding concern and complication to patients’ and physicians’ efforts to manage asthma symptoms.

“It is unfortunate to hear that more asthma inhalers are being discontinued,” Asthma and Allergy Foundation of America (AAFA) President and CEO Kenneth Mendez, said in an interview. The impact of Teva’s June 1 discontinuations of its Digihaler portfolio (ProAir Digihaler, AirDuo Digihaler, and ArmonAir Digihaler), he added, is only partially softened by Teva’s reassurance that its still-available RespiClick devices deliver the same drug formulations via the same devices as the ProAir and AirDuo products — because they lack the innovative digital component. “The Teva Digihaler portfolio had offered an innovative approach to encourage adherence to treatment by integrating a digital solution with an inhaler.”
 

Digital App Companion to Inhaler

The digital components of the AirDuo Digihaler (fluticasone propionate and salmeterol) inhalation powder and ArmonAir Digihaler (fluticasone propionate) inhalation powder, both maintenance inhalers for patients 12-years or older with asthma, include built-in Bluetooth^® wireless technology that connects to a companion mobile app. Their triggers for recording data on inhaler use are either the opening of the inhaler cap or the patient’s inhalation. The devices detect, record, and store data on inhaler use and peak inspiratory flow.

Also, they can remind the patient as to how often the devices have been used, measure inspiratory flow rates, and indicate when inhalation technique may need improvement. Data are then directly sent to the Digihaler app via Bluetooth technology, giving discretion to patients as to whether or not their data will be shared with health care providers.

When patients share their digital inhaler device-recorded data, Teva sources state, providers can more objectively assess the patients’ inhaler use patterns and habits to determine if they are using them as prescribed, and through inspiratory flow rates, judge whether or not patients may need inhaler technique coaching.
 

Possibility for Objective Data

“I was excited about the Digihaler when it was first launched,” said Maureen George, RN, PhD, of Columbia University School of Nursing, New York, “because it gave very good objective feedback on patients’ inhaler technique through peak inspiratory flow. It showed whether they missed doses or if there were patterns of increased use with increased symptoms.

“Inhaled medications are the only therapy that — if you inaccurately administer them — you don’t actually get any drug, at all,” she said in an interview. “If you don’t get the drug into the target organ, the lungs, you don’t get symptom relief, nor disease remission. Actually, most patients use their devices incorrectly, and most healthcare professionals can’t demonstrate correct delivery technique. At the pharmacy, you’re unlikely to see a real pharmacist, and more likely to see just a cashier. No other product that I know of has offered that degree of sophistication in terms of the different steps of inhaler technique.”
 

CONNECT2: Better Asthma Control at 24 Weeks

Benefits in asthma control for the Digihaler System have been confirmed recently in clinical research. The CONNECT2 trial compared asthma control with the Digihaler System (DS) versus standard of care (SoC) in patients 13 years or older with uncontrolled asthma (Asthma Control Test [ACT] score < 19). Investigators randomized them open-label 4:3 to the DS (n = 210) or SoC (n = 181) for 24 weeks. Primary endpoint assessment of the proportion of patients achieving well-controlled asthma (ie, an ACT score ≥ 20 or increase from baseline of ≥ 3 units at week 24) revealed an 88.7% higher probability that DS patients would have greater odds of achieving asthma control improvement at week 24, with 35% higher odds of asthma control in the DS group. Also, clinician-participant interactions, mostly addressing poor inhaler technique, were more frequent in the DS group. Six-month adherence was good (68.6%, vs 79.2% at month 1), and reliever use at month 6 was decreased by 38.2% from baseline in the DS group.

Lack of Inhaler Uptake

“It made me sad to hear that it was going away. It’s a device that should have been useful,” Dr. George said, “but the wonderful features that could have come at an individual level or at a population health level just were never realized. I don’t think it was from lack of trying on the company’s part, but when it was launched, insurance companies wouldn’t pay the extra cost that comes with having an integrated electronic monitoring device. They weren’t convinced that the return on investment down the road from improved disease control and fewer very expensive acute hospitalizations was worth it. So the uptake was poor.”

Where does this leave patients? Mr. Mendez stated, “It is imperative that people using Teva’s Digihaler products to treat their asthma reach out to their provider now to determine the best alternative treatment options. Unfortunately, when GSK discontinued Flovent, some people using that inhaler were transitioned to the ArmonAir Digihaler. Also, some formularies do not cover the authorized generic of Flovent, forcing patients to change treatment.”

The AAFA press release of April 15 lists in detail available alternatives to Teva’s discontinued devices, naming quick-relief inhalers and inhaled corticosteroids, noting where dosing, devices, or active ingredients are at variance from the Teva products. The AAFA document also lists and describes inhaler device types (metered dose inhaler, breath actuated inhaler, dry powder inhaler and soft mist inhaler) and their differences in detail.

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

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

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

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

ASUNCIÓN, PARAGUAY — The Lancet Diabetes & Endocrinology’s Commission for the Definition and Diagnosis of Clinical Obesity will soon publish criteria for distinguishing between clinical obesity and other preclinical phases. The criteria are intended to limit the negative connotations and misunderstandings associated with the word obesity and to clearly convey the idea that it is a disease and not just a condition that increases the risk for other pathologies.

One of the two Latin American experts on the 60-member commission, Ricardo Cohen, MD, PhD, coordinator of the Obesity and Diabetes Center at the Oswaldo Cruz German Hospital in São Paulo, Brazil, discussed this effort with this news organization.

The proposal being finalized would acknowledge a preclinical stage of obesity characterized by alterations in cells or tissues that lead to changes in organ structure, but not function. This stage can be measured by body mass index (BMI) or waist circumference.

The clinical stage occurs when “obesity already affects [the function of] organs, tissues, and functions like mobility. Here, it is a disease per se. And an active disease requires treatment,” said Dr. Cohen. The health risks associated with excess adiposity have already materialized and can be objectively documented through specific signs and symptoms.

Various experts from Latin America who participated in the XV Congress of the Latin American Obesity Societies (FLASO) and II Paraguayan Obesity Congress expressed to this news organization their reservations about the proposed name change and its practical effects. They highlighted the pros and cons of various terminologies that had been considered in recent years.

“Stigma undoubtedly exists. There’s also no doubt that this stigma and daily pressure on a person’s self-esteem influence behavior and condition a poor future clinical outcome because they promote denial of the disease. Healthcare professionals can make these mistakes. But I’m not sure that changing the name of a known disease will make a difference,” said Rafael Figueredo Grijalba, MD, president of FLASO and director of the Nutrition program at the Faculty of Health Sciences of the Nuestra Señora de la Asunción Catholic University in Paraguay.

Spotlight on Adiposity 

An alternative term for obesity proposed in 2016 by what is now the American Association of Clinical Endocrinology and by the American College of Endocrinology is “adiposity-based chronic disease (ABCD).” This designation “is on the right track,” said Violeta Jiménez, MD, internal medicine and endocrinology specialist at the Clinical Hospital of the National University of Asunción and the Comprehensive Diabetes Care Network of the Paraguay Social Security Institute.

The word obese is perceived as an insult, and the health impact of obesity is related to the quantity, distribution, and function of adipose tissue, said Dr. Jiménez. The BMI, the most used parameter in practice to determine overweight and obesity, “does not predict excess adiposity or determine a disease here and now, just as waist circumference does not confirm the condition.” 

Will the public be attracted to ABCD? What disease do these initials refer to, asked Dr. Jiménez. “What I like about the term ABCD is that it is not solely based on weight. It brings up the issue that a person who may not have obesity by BMI has adiposity and therefore has a disease brewing inside them.”

“Any obesity denomination is useful as long as the impact of comorbidities is taken into account, as well as the fact that it is not an aesthetic problem and treatment will be escalated aiming to benefit not only weight loss but also comorbidities,” said Paul Camperos Sánchez, MD, internal medicine and endocrinology specialist and head of research at La Trinidad Teaching Medical Center in Caracas, Venezuela, and former president of the Venezuelan Association for the Study of Obesity. 

Dr. Camperos Sánchez added that the classification of overweight and obesity into grades on the basis of BMI, which is recognized by the World Health Organization, “is the most known and for me remains the most comfortable. I will accept any other approach, but in my clinical practice, I continue to do it this way.” 

Fundamentally, knowledge can reduce social stigma and even prejudice from the medical community itself. “We must be respectful and compassionate and understand well what we are treating and the best way to approach each patient with realistic expectations. Evaluate whether, in addition to medication or intensive lifestyle changes, behavioral interventions or physiotherapy are required. If you don’t manage it well and find it challenging, perhaps that’s why we see so much stigmatization or humiliation of the patient. And that has nothing to do with the name [of the disease],” said Dr. Camperos Sánchez.

‘Biological Injustices’

Julio Montero, MD, nutritionist, president of the Argentine Society of Obesity and Eating Disorders, and former president of FLASO, told this news organization that the topic of nomenclatures “provides a lot of grounds for debate,” but he prefers the term “clinical obesity” because it has a medical meaning, is appropriate for statistical purposes, better conveys the concept of obesity as a disease, and distinguishes patients who have high weight or a spherical figure but may be free of weight-dependent conditions.

“Clinical obesity suggests that it is a person with high weight who has health problems and life expectancy issues related to excessive corpulence (weight-fat). The addition of the adjective clinical suggests that the patient has been evaluated by phenotype, fat distribution, hypertension, blood glucose, triglycerides, apnea, cardiac dilation, and mechanical problems, and based on that analysis, the diagnosis has been made,” said Dr. Montero.

Other positive aspects of the designation include not assuming that comorbidities are a direct consequence of adipose tissue accumulation because “lean mass often increases in patients with obesity, and diet and sedentary lifestyle also have an influence” nor does the term exclude people with central obesity. On the other hand, it does not propose a specific weight or fat that defines the disease, just like BMI does (which defines obesity but not its clinical consequences).

Regarding the proposed term ABCD, Montero pointed out that it focuses the diagnosis on the concept that adipose fat and adipocyte function are protagonists of the disease in question, even though there are chronic metabolic diseases like gout, porphyrias, and type 1 diabetes that do not depend on adiposity.

“ABCD also involves some degree of biological injustice, since femorogluteal adiposity (aside from aesthetic problems and excluding possible mechanical effects) is normal and healthy during pregnancy, lactation, growth, or situations of food scarcity risk, among others. Besides, it is an expression that is difficult to interpret for the untrained professional and even more so for communication to the population,” Dr. Montero concluded.

Dr. Cohen, Dr. Figueredo Grijalba, Dr. Jiménez, Dr. Camperos Sánchez, and Dr. Montero declared no relevant financial conflicts of interest. 

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

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

Probiotics appear to be beneficial for patients with cirrhosis, showing a reversal of hepatic encephalopathy (HE), improvement in liver function measures, and regulation of gut dysbiosis, according to a systematic review and meta-analysis.

They also improve quality of life and have a favorable safety profile, adding to their potential as a promising intervention for treating cirrhosis, the study authors wrote.

“As currently one of the top 10 leading causes of death globally, cirrhosis imposes a great health burden in many countries,” wrote lead author Xing Yang of the Health Management Research Institute at the People’s Hospital of Guangxi Zhuang Autonomous Region and Guangxi Academy of Medical Sciences in Nanning, China, and colleagues.

“The burden has escalated at the worldwide level since 1990, partly because of population growth and aging,” the authors wrote. “Thus, it is meaningful to explore effective treatments for reversing cirrhosis and preventing severe liver function and even systemic damage.”

The study was published online in Frontiers in Medicine .
 

Analyzing Probiotic Trials

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials among 2084 adults with cirrhosis, comparing the effects of probiotic intervention and control treatments, including placebo, no treatment, standard care, or active controls such as lactulose and rifaximin. The studies spanned 14 countries and included 1049 patients in the probiotic groups and 1035 in the control groups.

The research team calculated risk ratios (RRs) or standardized mean difference (SMD) for outcomes such as HE reversal, Model for End-Stage Liver Disease (MELD) scores, safety and tolerability of probiotics, liver function, and quality of life.

Among 17 studies involving patients with different stages of HE, as compared with the control group, probiotics significantly reversed minimal HE (RR, 1.54) and improved HE (RR, 1.94). In particular, the probiotic VSL#3 — which contains Streptococcus, Bifidobacterium, and Lactobacillus — produced more significant HE improvement (RR, 1.44) compared with other types of probiotics.

In addition, probiotics appeared to improve liver function by reducing MELD scores (SMD, −0.57) but didn’t show a difference in other liver function parameters. There were numerical but not significant reductions in mortality and serum inflammatory cytokine expression, including endotoxin, interleukin-6, and tumor necrosis factor-alpha.

Probiotics also improved quality-of-life scores (SMD, 0.51) and gut flora (SMD, 1.67). For gut flora, the numbers of the Lactobacillus group were significantly higher after probiotic treatment, but there wasn’t a significant difference for Bifidobacterium, Enterococcus, Bacteroidaceae, and Fusobacterium.

Finally, compared with control treatments, including placebo, standard therapy, and active controls such as lactulose and rifaximin, probiotics showed higher safety and tolerability profiles, causing a significantly lower incidence of serious adverse events (RR, 0.71).

Longer intervention times reduced the risk for overt HE development, hospitalization, and infections compared with shorter intervention times.

“Probiotics contribute to the reduction of ammonia levels and the improvement of neuropsychometric or neurophysiological status, leading to the reversal of HE associated with cirrhosis,” the study authors wrote. “Moreover, they induce favorable changes in gut flora and quality of life. Therefore, probiotics emerge as a promising intervention for reversing the onset of cirrhosis and preventing disease progression.”
 

Considering Variables

The authors noted several limitations, including a high or unclear risk for bias in 28 studies and the lack of data on the intervention effect for various types of probiotics or treatment durations.

“Overall, despite a number of methodological concerns, the study shows that probiotics can improve some disease markers in cirrhosis,” Phillipp Hartmann, MD, assistant professor of pediatric gastroenterology, hepatology, and nutrition at the University of California, San Diego, said in an interview.

“One of the methodological concerns is that the authors compared probiotics with a multitude of different treatments, including fiber and lactulose (which are both prebiotics), rifaximin (which is an antibiotic), standard of care, placebo, or no therapy,” he said. “This might contribute to the sometimes-contradictory findings between the different studies. The ideal comparison would be a specific probiotic formulation versus a placebo to understand what the probiotic actually does.”

Dr. Hartmann, who wasn’t involved with this study, has published a review on the potential of probiotics, prebiotics, and synbiotics in liver disease. He and colleagues noted the mechanisms that improve a disrupted intestinal barrier, microbial translocation, and altered gut microbiome metabolism.

“Over the last few years, we and others have studied the intestinal microbiota in various liver diseases, including alcohol-associated liver disease and metabolic dysfunction-associated steatotic liver disease,” he said. “Essentially, all studies support the notion that probiotics improve the microbial structure in the gut by increasing the beneficial and decreasing the potentially pathogenic microbes.”

However, probiotics and supplements are unregulated, Dr. Hartmann noted. Many different probiotic mixes and dosages have been tested in clinical trials, and additional studies are needed to determine the best formulations and dosages.

“Usually, the best outcomes can be achieved with a higher number of strains included in the probiotic formulation (10-30+) and a higher number of colony-forming units at 30-50+ billion per day,” he said.

The study was supported by funds from the Science and Technology Major Project of Guangxi, Guangxi Key Research and Development Program, and Natural Science Foundation of Guangxi Zhuang Autonomous Region. The authors declared no conflicts of interest. Dr. Hartmann reported no relevant disclosures.

A version of this article appeared on Medscape.com .

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

Two days a week of a medically supervised energy-restricted diet may lower blood glucose levels in adults with overweight or obesity and type 2 diabetes (T2D).

METHODOLOGY:

• Daily calorie restrictions and increased physical activity improve glycemic control and induce diabetes remission in patients with T2D, but these approaches are challenging to adhere to.
• Researchers tested whether 2 days a week (a 5:2 regimen) of either a very low-calorie formula diet or a “weekend warrior” physical activity pattern would be effective and more convenient.
• The three-arm IDEATE study enrolled 326 Asian participants with overweight or mild obesity (body mass index, 25.0-39.9) and T2D (diagnosed within prior 2 years; A1c, 7.0-8.9%; not on insulin) and randomly assigned them to receive a diet intervention, an exercise intervention, or routine lifestyle education (control group) for 12 weeks.
• The diet intervention group received an energy-restricted diet of 790 kcal/d on 2 days each week, and the exercise intervention group performed high-intensity interval training (4 minutes of aerobic activity, with a 10-minute total warm-up and cool-down) and resistance training twice a week (four exercises, two sets of eight to 12 repetitions).
• The primary outcome was the change in glycemic control between the diet or exercise intervention group and the control group after 12 weeks. Follow-up continued up to 1 year after intervention.

TAKEAWAY:

• Compared with the control group, patients in the diet intervention group achieved greater reductions in A1c after 12 weeks (difference, -0.34; P =.007), whereas A1c reductions in the exercise intervention group did not differ significantly from the control group.
• The likelihood of achieving diabetes remission was higher in the diet intervention vs the control group (adjusted odds ratio, 3.60; P = .008) but not in the exercise intervention group (P =.52).
• Body weight, body mass index, and high-density lipoprtein cholesterol levels were more effectively controlled in the diet intervention group only.
• However, participants in both the diet and exercise intervention groups showed reduced adiposity, liver fat content, and diastolic blood pressure compared with those in the control group.

IN PRACTICE:

“The diet intervention group experienced a greater energy deficit with a more pronounced metabolic benefit,” the authors wrote. “Our study suggests that a medically supervised 5:2 energy-restricted diet could serve as an alternative strategy for improving glycemic control.” 

SOURCE:

Mian Li, of the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, led the study, which was published online in Diabetes Care.

LIMITATIONS:

Body composition was analyzed using bioelectrical impedance analysis, which is a less accurate technique than dual-energy x-ray absorptiometry. The study used finger-prick tests to monitor blood glucose levels, which could have underestimated both hyperglycemic and hypoglycemic episodes. No information was collected on whether the participants maintained the diet or exercise regimen during the postintervention follow-up period.

DISCLOSURES:

This study was supported by the National Key Research and Development Program of China, National Natural Science Foundation of China, Shanghai Rising Star Program grant, and other sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

A new genetic variant in individuals who are APOE4 carriers is linked to a 70% reduction in the risk for Alzheimer’s disease, new research suggests.

The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.

While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.

The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.

“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.

The findings were published online in Acta Neuropathologica,
 

Combing Genetic Data

To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.

They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.

After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.

The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).

The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.

“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.

Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.

The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.

A version of this article appeared on Medscape.com.

A new genetic variant in individuals who are APOE4 carriers is linked to a 70% reduction in the risk for Alzheimer’s disease, new research suggests.

The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.

While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.

The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.

“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.

The findings were published online in Acta Neuropathologica,
 

Combing Genetic Data

To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.

They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.

After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.

The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).

The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.

“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.

Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.

The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.

A version of this article appeared on Medscape.com.

A new genetic variant in individuals who are APOE4 carriers is linked to a 70% reduction in the risk for Alzheimer’s disease, new research suggests.

The variant occurs on the fibronectin 1 (FN1) gene, which expresses fibronectin, an adhesive glycoprotein that lines the blood vessels at the blood-brain barrier and controls substances that move in and out of the brain.

While fibronectin is normally present in the blood-brain barrier in small amounts, individuals with Alzheimer’s disease tend to have it in excess. Normally, patients with Alzheimer’s disease have amyloid deposits that collect in the brain, but those with the FN1 variant appear to have the ability to amyloid from the brain before symptoms begin.

The researchers estimate that 1%-3% of APOE4 carriers in the United States — roughly 200,000-620,000 people — may have the protective mutation.

“Alzheimer’s disease may get started with amyloid deposits in the brain, but the disease manifestations are the result of changes that happen after the deposits appear,” Caghan Kizil, PhD, of Columbia University Vagelos College of Physicians and Surgeons in New York City, and a co-leader of the study, said in a press release.

The findings were published online in Acta Neuropathologica,
 

Combing Genetic Data

To find potentially protective Alzheimer’s disease variants, the investigators sequenced the genomes of more than 3500 APOE4 carriers older than 70 years with and without Alzheimer’s disease from various ethnic backgrounds.

They identified two variants on the FN1 gene, rs116558455 and rs140926439, present in healthy APOE4 carriers, that protected the APOE4 carriers against Alzheimer’s disease.

After Dr. Kizil and colleagues published their findings in a preprint, another research group that included investigators from Stanford and Washington Universities replicated the Columbia results in an independent sample of more than 7000 APOE4 carriers aged 60 years who were of European descent and identified the same FN1 variant.

The two research groups then combined their data on 11,000 participants and found that the FN1 variant rs140926439 was associated with a significantly reduced risk for Alzheimer’s disease in APOE4 carriers (odds ratio, 0.29; P = .014). A secondary analysis showed that the variant delayed Alzheimer’s disease symptom onset by 3.4 years (P = .025).

The investigators hope to use these findings to develop therapies to protect APOE4 carriers against Alzheimer’s disease.

“Anything that reduces excess fibronectin should provide some protection, and a drug that does this could be a significant step forward in the fight against this debilitating condition,” Dr. Kizil said.

Study limitations included a lack of longitudinal data on the relationship between amyloid concentration and fibronectin and the fact that investigators conducted the studies in clinically assessed individuals. Given the rare occurrence of the FN1 mutation, researchers do not have neuropathological assessments of study participants with the variant.

The study was funded by the National Institute on Aging, the Schaefer Research Scholars Program Award, Taub Institute Grants for Emerging Research, the National Institute of General Medical Sciences, and the Thompson Family Foundation Program for Accelerated Medicine Exploration in Alzheimer’s Disease and Related Disorders of the Nervous System. There were no disclosures reported.

A version of this article appeared on Medscape.com.

Gastroenterology

January 2024

Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.



Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.



Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.

February 2024

Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.



Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.



Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
 

Clinical Gastroenterology and Hepatology

January 2024

Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.

Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.

Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.

February 2024

Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.

Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
 

Techniques and Innovations in Gastrointestinal Endoscopy

January 2024

Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.

Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.



Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
 

Gastro Hep Advances

January 2024

Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.

Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.

Gastroenterology

January 2024

Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.



Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.



Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.

February 2024

Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.



Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.



Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
 

Clinical Gastroenterology and Hepatology

January 2024

Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.

Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.

Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.

February 2024

Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.

Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
 

Techniques and Innovations in Gastrointestinal Endoscopy

January 2024

Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.

Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.



Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
 

Gastro Hep Advances

January 2024

Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.

Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.

Gastroenterology

January 2024

Hirano I, et al; ASCENT WORKING GROUP. Ascending to New Heights for Novel Therapeutics for Eosinophilic Esophagitis. Gastroenterology. 2024 Jan;166(1):1-10. doi: 10.1053/j.gastro.2023.09.004. Epub 2023 Sep 9. PMID: 37690772; PMCID: PMC10872872.



Åkerström JH, et al. Antireflux Surgery Versus Antireflux Medication and Risk of Esophageal Adenocarcinoma in Patients With Barrett’s Esophagus. Gastroenterology. 2024 Jan;166(1):132-138.e3. doi: 10.1053/j.gastro.2023.08.050. Epub 2023 Sep 9. PMID: 37690771.



Barnes EL, et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024 Jan;166(1):59-85. doi: 10.1053/j.gastro.2023.10.015. PMID: 38128971.

February 2024

Yoo HW, et al. Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study. Gastroenterology. 2024 Feb;166(2):313-322.e3. doi: 10.1053/j.gastro.2023.10.013. Epub 2023 Oct 18. PMID: 37863270.



Yang J, et al. High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice. Gastroenterology. 2024 Feb;166(2):323-337.e7. doi: 10.1053/j.gastro.2023.10.012. Epub 2023 Oct 18. PMID: 37858797.



Young E, et al. Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial. Gastroenterology. 2024 Feb;166(2):338-340.e3. doi: 10.1053/j.gastro.2023.10.008. Epub 2023 Oct 14. PMID: 37839498.
 

Clinical Gastroenterology and Hepatology

January 2024

Overbeek KA, et al; Dutch Familial Pancreatic Cancer Surveillance Study work group. Intraductal Papillary Mucinous Neoplasms in High-Risk Individuals: Incidence, Growth Rate, and Malignancy Risk. Clin Gastroenterol Hepatol. 2024 Jan;22(1):62-71.e7. doi: 10.1016/j.cgh.2023.03.035. Epub 2023 Apr 7. PMID: 37031711.

Reddy CA, et al. Achalasia is Strongly Associated With Eosinophilic Esophagitis and Other Allergic Disorders. Clin Gastroenterol Hepatol. 2024 Jan;22(1):34-41.e2. doi: 10.1016/j.cgh.2023.06.013. Epub 2023 Jun 28. PMID: 37391057; PMCID: PMC10753026.

Thiruvengadam NR, et al. The Clinical Impact and Cost-Effectiveness of Surveillance of Incidentally Detected Gastric Intestinal Metaplasia: A Microsimulation Analysis. Clin Gastroenterol Hepatol. 2024 Jan;22(1):51-61. doi: 10.1016/j.cgh.2023.05.028. Epub 2023 Jun 9. Erratum in: Clin Gastroenterol Hepatol. 2024 Jan 19;: PMID: 37302442.

February 2024

Goodoory VC, et al. Systematic Review and Meta-analysis: Efficacy of Mesalamine in Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):243-251.e5. doi: 10.1016/j.cgh.2023.02.014. Epub 2023 Feb 27. PMID: 36858143.

Brenner DM, et al. Development and Current State of Digital Therapeutics for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2024 Feb;22(2):222-234. doi: 10.1016/j.cgh.2023.09.013. Epub 2023 Sep 22. PMID: 37743035.
 

Techniques and Innovations in Gastrointestinal Endoscopy

January 2024

Ramirez PR, et al. Gaps and Improvement Opportunities in Post-Colonoscopy Communication. Tech Innov Gastrointest Endosc. 2024 Jan;26(1):90-92. doi: 10.1016/j.tige.2023.10.001. Epub 2023 Oct 22.

Gonzaga ER, et al. Gastric Peroral Endoscopic Myotomy (G-POEM) for the Management of Gastroparesis. Tech Innov Gastrointest Endosc. 2024 Jan; 26(1): 46-55. doi: 10.1016/j.tige.2023.09.002. Epub 2023 Oct 13.



Wang D, et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2024 Jan;26(1): 30-37. doi: 10.1016/j.tige.2023.10.003. Epub 2023 Nov 8.
 

Gastro Hep Advances

January 2024

Adeniran E, et al. Intense and Sustained Alcohol Consumption Associated With Acute Pancreatitis Warrants Early Intervention. Gastro Hep Advances. 2024 Jan;3(1):61-63. doi: 10.1016/j.gastha.2023.08.017. Epub 2023 Sep 2.

Alkhouri N, et al. A Novel Prescription Digital Therapeutic Option for the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease. Gastro Hep Advances. 2024 Jan;3(1): 9-16. doi: 10.1016/j.gastha.2023.08.019. Epub 2023 Oct 1.

Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.

Washington University, St. Louis

Why Was the Future Leaders Program Conceived?

To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. Over time, both the AGA and the field of GI have grown in both size and complexity, which led to the vision of developing a pipeline of leaders who can understand the future challenges facing our field and understand the governance structure of the AGA to help lead it to face these challenges effectively.

Jennifer Layton, MBA

The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
 

How Does One Apply for the Program?

Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.

New York University

What Is Involved?

Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.

AGA

We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.

A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.

Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.

In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.^{1, 2}

Impact on the Field and Our Careers

Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.

To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.

In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
 

Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.

References

1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.

2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.

Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.

Washington University, St. Louis

Why Was the Future Leaders Program Conceived?

To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. Over time, both the AGA and the field of GI have grown in both size and complexity, which led to the vision of developing a pipeline of leaders who can understand the future challenges facing our field and understand the governance structure of the AGA to help lead it to face these challenges effectively.

Jennifer Layton, MBA

The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
 

How Does One Apply for the Program?

Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.

New York University

What Is Involved?

Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.

AGA

We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.

A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.

Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.

In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.^{1, 2}

Impact on the Field and Our Careers

Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.

To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.

In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
 

Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.

References

1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.

2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.

Two of us (Parakkal Deepak and Edward L. Barnes) were part of the American Gastroenterological Association’s (AGA) Future Leaders Program (FLP) class of 2022-2023, and our mentor was Aasma Shaukat. We were invited to share our experiences as participants in the FLP and its impact in our careers.

Washington University, St. Louis

Why Was the Future Leaders Program Conceived?

To understand this, one must first understand that the AGA, like all other GI professional organizations, relies on volunteer leaders to develop its long-term vision and execute this through strategic initiatives and programs. Over time, both the AGA and the field of GI have grown in both size and complexity, which led to the vision of developing a pipeline of leaders who can understand the future challenges facing our field and understand the governance structure of the AGA to help lead it to face these challenges effectively.

Jennifer Layton, MBA

The AGA FLP was thus conceived and launched in 2014-2015 by the founding chairs, Byron Cryer, MD, who is a professor of medicine and associate dean for faculty diversity at University of Texas Southwestern Medical School and Suzanne Rose, MD, MSEd, AGAF, who is a professor of medicine and senior vice dean for medical education at Perelman School of Medicine at the University of Pennsylvania. They envisioned a leadership pathway that would position early career GIs on a track to positively affect the AGA and the field of GI.
 

How Does One Apply for the Program?

Our FLP cohort applications were invited in October of 2021 and mentees accepted into the program in November 2021. The application process is competitive – applicants are encouraged to detail why they feel they would benefit from the FLP, what existing skillsets they have that can be further enhanced through the program, and what their long-term vision is for their growth as leaders, both within their institution and within the AGA. This is further accompanied by letters of support from their divisional chiefs and other key supervisors within the division who are intimately aware of their leadership potential and career trajectory. This process identified 18 future leaders for our class of 2022-2023.

New York University

What Is Involved?

Following acceptance into the AGA Future Leaders Program, we embarked on a series of virtual and in-person meetings with our mentorship triads (one mentor and two mentees) and other mentorship teams over the 18-month program (see Figure). These meetings covered highly focused topics ranging from the role of advocacy in leadership to negotiation and developing a business plan, with ample opportunities for individually tailored mentorship within the mentorship triads.

AGA

We also completed personality assessments that helped us understand our strengths and areas of improvement, and ways to use the information to hone our leadership styles.

A large portion of programming and the mentorship experience during the AGA Future Leaders Program is focused on a leadership project that is aimed at addressing a societal driver of interest for the AGA. Examples of these societal drivers of interest include maximizing the role of women in gastroenterology, the role of artificial intelligence in gastroenterology, burnout, and the impact of climate change on gastroenterology. Mentorship triads propose novel methods for addressing these critical issues, outlining the roles that the AGA and other stakeholders may embrace to address these anticipated growing challenges head on.

Our mentorship triad was asked to address the issue of ending disparities within gastroenterology. Given our research and clinical interest in inflammatory bowel disease (IBD), we immediately recognized an opportunity to evaluate and potentially offer solutions for the geographic disparities that exist in the field of IBD. These disparities affect access to care for patients with Crohn’s disease and ulcerative colitis, leading to delays in diagnosis and ultimately effective therapy decisions.

In addition to developing a proposal for the AGA to expand access to care to major IBD centers in rural areas where these disparities exist, we also initiated an examination of geographic disparities in our own multidisciplinary IBD centers (abstract accepted for presentation at Digestive Diseases Week 2024). This allowed us to expand our respective research footprints at our institutions, utilizing new methods of geocoding to directly measure factors affecting clinical outcomes in IBD. Given our in-depth evaluation of this topic as part of our Future Leaders Program training, at the suggestion of our mentor, our mentorship triad also published a commentary on geographic disparities in the Diversity, Equity, and Inclusion sections of Gastroenterology and Clinical Gastroenterology and Hepatology.^{1, 2}

Impact on the Field and Our Careers

Our mentorship triad had the unique experience of having a mentor who had previously participated in the Future Leaders Program as a mentee. As the Future Leaders Program has now enrolled 72 participants, these occasions will likely become more frequent, given the opportunities for career development and growth within the AGA (and our field) that are available after participating in the Future Leaders Program.

To have a mentor with this insight of having been a mentee in the program was invaluable, given her direct experience and understanding of the growth opportunities available, and opportunities to maximize participation in the Future Leaders Program. Additionally, as evidenced by Dr. Shaukat’s recommendations to grow our initial assignment into published commentaries, need statements for our field, and ultimately growing research projects, her keen insights as a mentor were a critical component of our individual growth in the program and the success of our mentorship triad. We benefited from networking with peers and learning about their work, which can lead to future collaborations. We had access to the highly accomplished mentors from diverse settings and learned models of leadership, while developing skills to foster our own leadership style.

In terms of programmatic impact, more than 90% of FLP alumni are serving in AGA leadership on committees, task forces, editorial boards, and councils. What is also important is the impact of content developed by mentee-mentor triads during the FLP cohorts over time. More than 700 GIs have benefited from online leadership development content created by the FLP. Based on our experience, we highly recommend all early career GI physicians to apply!
 

Dr. Parakkal (@P_DeepakIBDMD) is based in the division of gastroenterology, Washington University in St. Louis (Mo.) School of Medicine. He is supported by a Junior Faculty Development Award from the American College of Gastroenterology and IBD Plexus of the Crohn’s & Colitis Foundation. He has received research support under a sponsored research agreement unrelated to the data in the paper from AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Prometheus Biosciences, Takeda Pharmaceuticals, Roche-Genentech, and CorEvitas LLC. He has served as a consultant for AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Scipher Medicine, Fresenius Kabi, Roche-Genentech, and CorEvitas LLC. Dr. Barnes (@EdBarnesMD) is based in the division of gastroenterology and hepatology, University of North Carolina at Chapel Hill. He is supported by National Institutes of Health K23DK127157-01, and has served as a consultant for Eli Lilly, Bristol-Meyers Squibb, and Target RWE. Dr. Shaukat (@AasmaShaukatMD) is based in the division of gastroenterology, New York University, New York. She has served as a consultant for Iterative health, Motus, Freenome, and Geneoscopy. Research support by the Steve and Alex Cohen Foundation.

References

1. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Gastroenterology. 2023 July. doi: 10.1053/j.gastro.2023.05.017.

2. Deepak P, Barnes EL, Shaukat A. Health Disparities in Inflammatory Bowel Disease Care Driven by Rural Versus Urban Residence: Challenges and Potential Solutions. Clin Gastroenterol Hepatol. 2023 July. doi: 10.1016/j.cgh.2023.04.006.

A unique autoantibody signature of multiple sclerosis (MS) is detectable in the blood of people with the disease years before symptom onset, according to a new study.

Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.

A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis. 

“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.

Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said. 

The study was published online in Nature Medicine.
 

Seeking Earlier Diagnosis

Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.

These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients. 

To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.

Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.

Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points. 
 

Early Signs of Injury

In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.

Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis. 

Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.

The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.

The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature. 

The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS. 

“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
 

Not Ready for Prime Time

Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.” 

Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.

Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”

Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.

This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study. 

A version of this article appeared on Medscape.com.

A unique autoantibody signature of multiple sclerosis (MS) is detectable in the blood of people with the disease years before symptom onset, according to a new study.

Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.

A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis. 

“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.

Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said. 

The study was published online in Nature Medicine.
 

Seeking Earlier Diagnosis

Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.

These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients. 

To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.

Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.

Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points. 
 

Early Signs of Injury

In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.

Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis. 

Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.

The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.

The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature. 

The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS. 

“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
 

Not Ready for Prime Time

Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.” 

Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.

Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”

Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.

This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study. 

A version of this article appeared on Medscape.com.

A unique autoantibody signature of multiple sclerosis (MS) is detectable in the blood of people with the disease years before symptom onset, according to a new study.

Investigators screened blood samples from 250 individuals with MS drawn 5 years before and 1 year after symptom onset, profiled MS-related autoantibodies, and compared the sample with 250 matched controls.

A unique cluster of autoantibodies was found in 10% of people with MS, appearing up to 5 years before the onset of clinical symptoms and remaining higher 1 year after diagnosis. 

“Our work demonstrates that a subset of MS patients has antibodies that react to a common protein motif, both before, during, and after diagnosis and symptom onset,” said lead investigator Colin R. Zamecnik, PhD, a postdoctoral researcher at UCSF School of Medicine, University of California, San Francisco.

Such a discovery could aid in early diagnosis, Dr. Zamecnik added. MS treatments “have gotten much better in the last 15-20 years and evidence shows early treatment can improve outcomes,” he said. 

The study was published online in Nature Medicine.
 

Seeking Earlier Diagnosis

Previous research shows that nonspecific neurologic episodes occur more frequently in people who received an MS diagnosis later in life, pointing to the possibility of an MS prodrome, the authors noted.

These neurologic episodes may be indicative of ongoing neuroinflammatory processes in the preclinical period, they added. Studies in several other autoimmune diseases show that diagnostic autoantibodies can appear years before symptom onset. However, no such antibodies have previously been identified in MS patients. 

To investigate, the researchers turned to data from a large, prospective incident MS cohort assembled during the Gulf War era in more than 10 million US military veterans.

Records of those with the earliest diagnosis (an average of 5 years before symptom onset) and 1 year after the first attack were analyzed, and matched controls were selected.

Investigators used a technique called phage display immunoprecipitation sequencing to screen human blood for antibodies. They conducted a whole-proteome autoantibody screen and serum neurofilament light (sNfL) measurements on these samples in both case patients and controls at the same time points. 
 

Early Signs of Injury

In the preclinical serum samples, sNfL levels were higher nearer the date of diagnosis and significantly higher in post- versus pre-onset samples in people with MS. “Together, these data provide evidence that at least some people with MS exhibit early signs of neuroaxonal injury long before onset of symptoms,” the authors noted.

Analysis of the collection of peptides, described by the investigators as an “autoantibody signature,” was consistent over time and was present regardless of diagnosis. 

Further analysis of the autoantibodies revealed a characteristic protein motif found in common viruses, including Epstein-Barr virus (EBV) and hepatitis C virus, among others.

The motif “shares remarkable similarity to those found on many pathogens that infect humans, including EBV, which is known to be a risk factor for development of MS,” Dr. Zamecnik said.

The researchers validated these findings by analyzing serum and cerebrospinal fluid samples from participants in ORIGINS, an MS cohort at the University of California, San Francisco, that enrolled patients at clinical onset. As with the other cohort, 10% of patients had the autoantibody signature. 

The investigators added that the findings detail some of the first autoantigen-specific biomarkers found in preclinical MS. 

“Taken together, our future work will focus on profiling these patients more closely over time to see how they differ from their counterparts and gives further evidence of viral-host crosstalk as a hallmark of this disease,” Dr. Zamecnik said.
 

Not Ready for Prime Time

Commenting on the findings, Bruce Bebo, PhD, executive vice president of research, National Multiple Sclerosis Society, said the study corroborates the “growing appreciation that MS has a prodrome.” 

Such a discovery might “accelerate progress toward the possibility of treating MS ever-earlier in the course of the disease, or possibly even preventing MS from occurring in the first place,” he added.

Dr. Bebo, who was not involved in this research, noted that it was conducted at a single center, is only preliminary, and “has no immediate clinical applicability.”

Also, because this pattern was identified in only 10% of individuals with MS, “an additional hurdle is whether we can identify other patterns in greater numbers of people,” he added.

This work was supported by the Valhalla Foundation; the Weill Neurohub; the Westridge Foundation; the National Institute of Neurological Disorders and Stroke; the National Institute of Allergy and Infectious Diseases; National Multiple Sclerosis Society; the Department of Defense; the German Society of Multiple Sclerosis; the Water Cove Charitable Foundation; Tim and Laura O’Shaughnessy; the Littera Family; School of Medicine Dean’s Yearlong Fellowship, supported by residual funds from the Howard Hughes Medical Institute Medical Fellows at UCSF; the Chan Zuckerberg Biohub San Francisco; the John A. Watson Scholar Program at UCSF; the Hanna H. Gray Fellowship, Howard Hughes Medical Institute; the National Institutes of Health; and the University of California President’s Postdoctoral Fellowship Program. Dr. Zamecnik received funding toward this study from the National Multiple Sclerosis Society and the Water Cove Charitable Foundation. He declared no competing financial interests. The other authors’ disclosures are listed on the original paper. Dr. Bebo is the executive vice president of the National Multiple Sclerosis Society, which provided support for the study. 

A version of this article appeared on Medscape.com.

Dear colleagues,

Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.

In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.

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

Artificial Intelligence in Gastrointestinal Endoscopy

BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD

The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.

Baylor College of Medicine

Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.⁴ Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.⁵

Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.⁶ In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.⁷ The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.

Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.

Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.

Innovative applications for alternative gastrointestinal conditions

Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.

Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.^8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.¹¹ Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.^12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.

Artificial intelligence adoption in clinical practice

Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.

Conclusions

Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.

Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.

References

1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.

2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.

3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.

4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.

5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.

6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.

7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.

8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.

9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.

10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.

11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.

12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.

13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.

The Promise and Challenges of AI in Hepatology

BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL

In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.

The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.

Yale School of Medicine

Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.

AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.

New York Medical College

Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.

Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.

In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.

We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.

Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.

Sources

Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.

Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.

Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.

Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.

Dear colleagues,

Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.

In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.

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

Artificial Intelligence in Gastrointestinal Endoscopy

BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD

The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.

Baylor College of Medicine

Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.⁴ Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.⁵

Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.⁶ In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.⁷ The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.

Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.

Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.

Innovative applications for alternative gastrointestinal conditions

Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.

Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.^8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.¹¹ Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.^12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.

Artificial intelligence adoption in clinical practice

Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.

Conclusions

Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.

Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.

References

1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.

2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.

3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.

4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.

5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.

6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.

7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.

8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.

9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.

10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.

11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.

12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.

13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.

The Promise and Challenges of AI in Hepatology

BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL

In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.

The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.

Yale School of Medicine

Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.

AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.

New York Medical College

Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.

Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.

In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.

We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.

Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.

Sources

Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.

Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.

Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.

Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.

Dear colleagues,

Since our prior Perspectives piece on artificial intelligence (AI) in GI and Hepatology in 2022, the field has seen almost exponential growth. Expectations are high that AI will revolutionize our field and significantly improve patient care. But as the global discussion on AI has shown, there are real challenges with adoption, including issues with accuracy, reliability, and privacy.

In this issue, Dr. Nabil M. Mansour and Dr. Thomas R. McCarty explore the current and future impact of AI on gastroenterology, while Dr. Basile Njei and Yazan A. Al Ajlouni assess its role in hepatology. We hope these pieces will help your discussions in incorporating or researching AI for use in your own practices. We welcome your thoughts on this issue on X @AGA_GIHN.

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

Artificial Intelligence in Gastrointestinal Endoscopy

BY THOMAS R. MCCARTY, MD, MPH; NABIL M. MANSOUR, MD

The last few decades have seen an exponential increase and interest in the role of artificial intelligence (AI) and adoption of deep learning algorithms within healthcare and patient care services. The field of gastroenterology and endoscopy has similarly seen a tremendous uptake in acceptance and implementation of AI for a variety of gastrointestinal conditions. The spectrum of AI-based applications includes detection or diagnostic-based as well as therapeutic assistance tools. From the first US Food and Drug Administration (FDA)-approved device that uses machine learning to assist clinicians in detecting lesions during colonoscopy, to other more innovative machine learning techniques for small bowel, esophageal, and hepatobiliary conditions, AI has dramatically changed the landscape of gastrointestinal endoscopy.

Baylor College of Medicine

Ultimately, this data led to FDA approval of the CADe system GI Genius (Medtronic, Dublin, Ireland) in 2021.⁴ Additional systems have since been FDA approved or 510(k) cleared including Endoscreener (Wision AI, Shanghai, China), SKOUT (Iterative Health, Cambridge, Massachusetts), MAGENTIQ-COLO (MAGENTIQ-EYE LTD, Haifa, Israel), and CAD EYE (Fujifilm, Tokyo), all of which have shown increased ADR and/or increased APC and/or reduced adenoma miss rates in randomized trials.⁵

Yet despite the promise of improved quality and subsequent translation to better patient outcomes, there has been a noticeable disconnect between RCT data and more real-world literature.⁶ In a recent study, no improvement was seen in ADR after implementation of a CADe system for colorectal cancer screening — including both higher and lower-ADR performers. Looking at change over time after implementation, CADe had no positive effect in any group over time, divergent from early RCT data. In a more recent multicenter, community-based RCT study, again CADe did not result in a statistically significant difference in the number of adenomas detected.⁷ The differences between some of these more recent “real-world” studies vs the majority of data from RCTs raise important questions regarding the potential of bias (due to unblinding) in prospective trials, as well as the role of the human-AI interaction.

Importantly for RCT data, both cohorts in these studies met adequate ADR benchmarks, though it remains unclear whether a truly increased ADR necessitates better patient outcomes — is higher always better? In addition, an important consideration with evaluating any AI/CADe system is that they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using an outdated version of a CADe system.

Additional unanswered questions regarding an ideal ADR for implementation, preferred patient populations for screening (especially for younger individuals), and the role and adoption of computer-aided polyp diagnosis/characterization (CADx) within the United States remain. Furthermore, questions regarding procedural withdrawal time, impact on sessile serrated lesion detection, cost-effectiveness, and preferred adoption strategies have begun to be explored, though require more data to better define a best practice approach. Ultimately, answers to some of these unknowns may explain the discordant results and help guide future implementation measures.

Innovative applications for alternative gastrointestinal conditions

Given the fervor and excitement, as well as the outcomes associated with AI-based colorectal screening, it is not surprising these techniques have been expanded to other gastrointestinal conditions. At this time, all of these are fledgling, mostly single-center tools, not yet ready for widespread adoption. Nonetheless, these represent a potentially important step forward for difficult-to-manage gastrointestinal diseases.

Machine learning CADe systems have been developed to help identify early Barrett’s neoplasia, depth and invasion of gastric cancer, as well as lesion detection in small bowel video capsule endoscopy.^8-10 Endoscopic retrograde cholangiopancreatography (ERCP)-based applications for cholangiocarcinoma and indeterminate stricture diagnosis have also been studied.¹¹ Additional AI-based algorithms have been employed for complex procedures such as endoscopic submucosal dissection (ESD) or peroral endoscopic myotomy (POEM) to delineate vessels, better define tissue planes for dissection, and visualize landmark structures.^12,13 Furthermore, AI-based scope guidance/manipulation, bleeding detection, landmark identification, and lesion detection have the potential to revolutionize endoscopic training and education. The impact that generative AI can potentially have on clinical practice is also an exciting prospect that warrants further investigation.

Artificial intelligence adoption in clinical practice

Clinical practice with regard to AI and colorectal cancer screening largely mirrors the disconnect in the current literature, with “believers” and “non-believers” as well as innovators and early adopters alongside laggards. In our own academic practices, we continue to struggle with the adoption and standardized implementation of AI-based colorectal cancer CADe systems, despite the RCT data showing positive results. It is likely that AI uptake will follow the technology predictions of Amara’s Law — i.e., individuals tend to overestimate the short-term impact of new technologies while underestimating long-term effects. In the end, more widespread adoption in community practice and larger scale real-world clinical outcomes studies are likely to determine the true impact of these exciting technologies. For other, less established AI-based tools, more data are currently required.

Conclusions

Ultimately, AI-based algorithms are likely here to stay, with continued improvement and evolution to occur based on provider feedback and patient care needs. Current tools, while not all-encompassing, have the potential to dramatically change the landscape of endoscopic training, diagnostic evaluation, and therapeutic care. It is critically important that relevant stakeholders, both endoscopists and patients, be involved in future applications and design to improve efficiency and quality outcomes overall.

Dr. McCarty is based in the Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital. Dr. Mansour is based in the section of gastroenterology, Baylor College of Medicine, Houston. Dr. McCarty reports no conflicts of interest. Dr. Mansour reports having been a consultant for Iterative Health.

References

1. Repici A, et al. Efficacy of real-time computer-aided detection of colorectal neoplasia in a randomized trial. Gastroenterology. 2020 Aug. doi: 10.1053/j.gastro.2020.04.062.

2. Repici A, et al. Artificial intelligence and colonoscopy experience: Lessons from two randomised trials. Gut. Apr 2022. doi: 10.1136/gutjnl-2021-324471.

3. Wallace MB, et al. Impact of artificial intelligence on miss rate of colorectal neoplasia. Gastroenterology 2022 Jul. doi: 10.1053/j.gastro.2022.03.007.

4. United States Food and Drug Administration (FDA). GI Genius FDA Approval [April 9, 2021]. Accessed January 5, 2022. Available at: www.accessdata.fda.gov/cdrh_docs/pdf21/K211951.pdf.

5. Maas MHJ, et al. A computer-aided polyp detection system in screening and surveillance colonoscopy: An international, multicentre, randomised, tandem trial. Lancet Digit Health. 2024 Mar. doi: 10.1016/S2589-7500(23)00242-X.

6. Ladabaum U, et al. Computer-aided detection of polyps does not improve colonoscopist performance in a pragmatic implementation trial. Gastroenterology. 2023 Mar. doi: 10.1053/j.gastro.2022.12.004.

7. Wei MT, et al. Evaluation of computer-aided detection during colonoscopy in the community (AI-SEE): A multicenter randomized clinical trial. Am J Gastroenterol. 2023 Oct. doi: 10.14309/ajg.0000000000002239.

8. de Groof J, et al. The Argos project: The development of a computer-aided detection system to improve detection of Barrett’s neoplasia on white light endoscopy. United European Gastroenterol J. 2019 May. doi: 10.1177/2050640619837443.

9. Kanesaka T, et al. Computer-aided diagnosis for identifying and delineating early gastric cancers in magnifying narrow-band imaging. Gastrointest Endosc. 2018 May. doi: 10.1016/j.gie.2017.11.029.

10. Sahafi A, et al. Edge artificial intelligence wireless video capsule endoscopy. Sci Rep. 2022 Aug. doi: 10.1038/s41598-022-17502-7.

11. Njei B, et al. Artificial intelligence in endoscopic imaging for detection of malignant biliary strictures and cholangiocarcinoma: A systematic review. Ann Gastroenterol. 2023 Mar-Apr. doi: 10.20524/aog.2023.0779.

12. Ebigbo A, et al. Vessel and tissue recognition during third-space endoscopy using a deep learning algorithm. Gut. 2022 Dec. doi: 10.1136/gutjnl-2021-326470.

13. Cao J, et al. Intelligent surgical workflow recognition for endoscopic submucosal dissection with real-time animal study. Nat Commun. 2023 Oct. doi: 10.1038/s41467-023-42451-8.

The Promise and Challenges of AI in Hepatology

BY BASILE NJEI, MD, MPH, PHD; YAZAN A. AL-AJLOUNI, MPHIL

In the dynamic realm of medicine, artificial intelligence (AI) emerges as a transformative force, notably within hepatology. The discipline of hepatology, dedicated to liver and related organ diseases, is ripe for AI’s promise to revolutionize diagnostics and treatment, pushing toward a future of precision medicine. Yet, the path to fully realizing AI’s potential in hepatology is laced with data, ethical, and integration challenges.

The application of AI, particularly in histopathology, significantly enhances disease diagnosis and staging in hepatology. AI-driven approaches remedy traditional histopathological challenges, such as interpretative variability, providing more consistent and accurate disease analyses. This is especially evident in conditions like metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma (HCC), where AI aids in identifying critical gene signatures, thereby refining therapy selection.

Yale School of Medicine

Similarly, deep learning (DL), a branch of AI, has attracted significant interest globally, particularly in image recognition. AI’s incorporation into medical imaging marks a significant advancement, enabling early detection of malignancies like HCC and improving diagnostics in steatotic liver disease through enhanced imaging analyses using convolutional neural networks (CNN). The abundance of imaging data alongside clinical outcomes has catalyzed AI’s integration into radiology, leading to the swift growth of radiomics as a novel domain in medical research.

AI has also been shown to identify nuanced alterations in electrocardiograms (EKGs) associated with liver conditions, potentially detecting the progression of liver diseases at an earlier stage than currently possible. By leveraging complex algorithms and machine learning, AI can analyze EKG patterns with a precision and depth unattainable through traditional manual interpretation. Given that liver diseases, such as cirrhosis or hepatitis, can induce subtle cardiac changes long before other clinical symptoms manifest, early detection through AI-enhanced EKG analysis could lead to timely interventions, potentially halting or reversing disease progression. This approach further enriches our understanding of the intricate interplay between liver function and cardiac health, highlighting the potential for AI to transform not just liver disease diagnostics but also to foster a more integrated approach to patient care.

New York Medical College

Beyond diagnostics, the burgeoning field of generative AI introduces groundbreaking possibilities in treatment planning and patient education, particularly for chronic conditions like cirrhosis. Generative AI produces original content, including text, visuals, and music, by identifying and learning patterns from its training data. When it leverages large language models (LLMs), it entails training on vast collections of textual data and using AI models characterized by many parameters. A notable instance of generative AI employing LLMs is ChatGPT (General Pretrained Transformers). By simulating disease progression and treatment outcomes, generative AI can foster personalized treatment strategies and empower patients with knowledge about their health trajectories. Yet, realizing these potential demands requires overcoming data quality and interpretability challenges, and ensuring AI outputs are accessible and actionable for clinicians and patients.

Despite these advancements, leveraging AI in hepatology is not devoid of hurdles. The development and training of AI models require extensive and diverse datasets, raising concerns about data privacy and ethical use. Addressing these concerns is paramount for successfully integrating AI into clinical hepatology practice, necessitating transparent algorithmic processes and stringent ethical standards. Ethical considerations are central to AI’s integration into hepatology. Algorithmic biases, patient privacy, and the impact of AI-driven decisions underscore the need for cautious AI deployment. Developing transparent, understandable algorithms and establishing ethical guidelines for AI use are critical steps towards ethically leveraging AI in patient care.

In conclusion, AI’s integration into hepatology holds tremendous promise for advancing patient care through enhanced diagnostics, treatment planning, and patient education. Overcoming the associated challenges, including ethical concerns, data diversity, and algorithm interpretability, is crucial. As the hepatology community navigates this technological evolution, a balanced approach that marries technological advancements with ethical stewardship will be key to harnessing AI’s full potential, ensuring it serves the best interests of patients and propels the field of hepatology into the future.

We predict a trajectory of increased use and adoption of AI in hepatology. AI in hepatology is likely to meet the test of pervasiveness, improvement, and innovation. The adoption of AI in routine hepatology diagnosis and management will likely follow Amara’s law and the five stages of the hype cycle. We believe that we are still in the infant stages of adopting AI technology in hepatology, and this phase may last 5 years before there is a peak of inflated expectations. The trough of disillusionment and slopes of enlightenment may only be observed in the next decades.

Dr. Njei is based in the Section of Digestive Diseases, Yale School of Medicine, New Haven, Conn. Mr. Al-Ajlouni is a senior medical student at New York Medical College School of Medicine, Valhalla, N.Y. They have no conflicts of interest to declare.

Sources

Taylor-Weiner A, et al. A Machine Learning Approach Enables Quantitative Measurement of Liver Histology and Disease Monitoring in NASH. Hepatology. 2021 Jul. doi: 10.1002/hep.31750.

Zeng Q, et al. Artificial intelligence predicts immune and inflammatory gene signatures directly from hepatocellular carcinoma histology. J Hepatol. 2022 Jul. doi: 10.1016/j.jhep.2022.01.018.

Ahn JC, et al. Development of the AI-Cirrhosis-ECG Score: An Electrocardiogram-Based Deep Learning Model in Cirrhosis. Am J Gastroenterol. 2022 Mar. doi: 10.14309/ajg.0000000000001617.

Nduma BN, et al. The Application of Artificial Intelligence (AI)-Based Ultrasound for the Diagnosis of Fatty Liver Disease: A Systematic Review. Cureus. 2023 Dec 15. doi: 10.7759/cureus.50601.