This transcript has been edited for clarity.
 

Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?

Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.

Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?

Dr. Herbenick: I’ve done a lot of research related to pleasure and orgasm, some related to the different styles of touch, some related to vibrator use, showing that more than half of women reported having ever used a vibrator. The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.

Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”

Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.

Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.

Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.

Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.

Dr. Herbenick: Absolutely.

Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?

Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.

Dr. Rubin: Thank you so much for joining us today.

Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity.
 

Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?

Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.

Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?

Dr. Herbenick: I’ve done a lot of research related to pleasure and orgasm, some related to the different styles of touch, some related to vibrator use, showing that more than half of women reported having ever used a vibrator. The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.

Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”

Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.

Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.

Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.

Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.

Dr. Herbenick: Absolutely.

Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?

Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.

Dr. Rubin: Thank you so much for joining us today.

Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

This transcript has been edited for clarity.
 

Rachel S. Rubin, MD: Hi, everybody. Welcome back to another episode of Sex Matters. I am Dr Rachel Rubin. I’m a urologist and sexual medicine specialist in the Washington, DC, area, and I am thrilled to bring you this next guest. This is someone I am a huge fan of. I have been following her research for decades now, and we are so blessed to have her: Debby Herbenick. Why don’t you introduce yourself and tell people all about your research?

Debby Herbenick, PhD: I’m a professor at the Indiana University School of Public Health, and I’ve been a sexuality researcher and educator for about 25 years. I’ve studied issues related to women’s orgasm, vibrator use, how people feel about their genitals, and how that impacts whether or not they are comfortable seeking healthcare. Most recently, I’ve been looking at emerging sexual practices.

Dr. Rubin: You can’t be in sexual medicine without knowing Dr. Herbenick’s work. It is just instrumental to our knowledge about what people are actually doing, what people care about, and what’s happening out there. Probably not a day goes by that I don’t quote your research on how women experience sexual pleasure, how women orgasm. Can you talk briefly about that research?

Dr. Herbenick: I’ve done a lot of research related to pleasure and orgasm, some related to the different styles of touch, some related to vibrator use, showing that more than half of women reported having ever used a vibrator. The key is really variety. People need to feel comfortable with the way that they experience their bodies and their own paths to pleasure, and feel supported in being able to explore in that way.

Dr. Rubin: And what are some resources? What I often quote is that everyone thinks, because of Hollywood and pornography, that women orgasm from vaginal penetration alone, which of course we know physiologically doesn’t make sense. The numbers are staggering. People often go to their doctor and say: “I’m not normal. I can’t orgasm from penetration. Is there something wrong with me?”

Dr. Herbenick: Most women are not orgasming from vaginal intercourse alone. Many have added direct clitoral stimulation. Others prefer to receive oral sex. Some are having orgasms with a vibrator or other kinds of sex toys. And for some, it’s not just the behavior, right? It’s having the behavior in a certain amount of intimacy or connection with a partner, so really focusing on that as well.

Dr. Rubin: Your data show that more than 50% of women have used vibration in the past. I tell my male patients as well that the penis and the clitoris are the same. The penis likes vibration too, but many have never tried it. As a clinician, being able to encourage patients to use these devices and tools is really important. Your data help us show that this is an important aspect of pleasure.

Dr. Herbenick: I’m always glad to hear they’re helpful. And, of course, our research really focused on vibrators, but it’s been so interesting to see the sexual enhancement products change over the years. And now we have all these air pressure toys, too, which are especially useful for people who really can’t take or don’t prefer direct contact with their clitoris or other genital parts.

Dr. Rubin: I tell my patients all the time that the sex devices that we use today are not the same things from back in the day. There are so many high technological advances in this space that are really wonderful tools for me as a doctor, that I can really help my patients understand and use just to have more fun.

Dr. Herbenick: Absolutely.

Dr. Rubin: Very few of us are sexual medicine–trained physicians who feel confident and comfortable talking about sexual health issues. How can they find you or follow you?

Dr. Herbenick: I’m on social media as Debby Herbenick. I’m also on our website at Indiana University, the Center for Sexual Health Promotion.

Dr. Rubin: Thank you so much for joining us today.

Rachel S. Rubin, MD, is assistant clinical professor, Department of Urology, Georgetown University, Washington, DC, and in private practice in North Bethesda, Maryland. She disclosed financial relationships with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

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

Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.

In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.


Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?

Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.

The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.


Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?

Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.


Q: What’s new about this kind of research?

Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.


Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?

Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.

In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.

This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.


Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?

Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.

[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]



Q: What makes this drug unique?

Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.



Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?

Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.

This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.



Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?

Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.

Dr. Kamal has no disclosures to report.

Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.

In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.


Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?

Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.

The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.


Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?

Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.


Q: What’s new about this kind of research?

Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.


Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?

Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.

In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.

This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.


Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?

Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.

[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]



Q: What makes this drug unique?

Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.



Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?

Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.

This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.



Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?

Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.

Dr. Kamal has no disclosures to report.

Research presented at the annual meeting of the American Society of Clinical Oncology (ASCO) has the potential to change practice — and assumptions — about acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and blood cancer as a whole, according to the chief science officer of the American Cancer Society.

In an interview following the conference, Arif H. Kamal, MD, MBA, MHS, who practices hematology-oncology at Duke University, Durham, North Carolina, recapped several landmark studies and discussed their lessons for clinicians.


Question: You’ve highlighted a randomized, multisite clinical trialled by a researcher from Massachusetts General Hospital in Boston. The researchers enrolled 115 adult patients with AML or high-risk myelodysplastic syndrome (MDS) who were receiving non–intensive care to usual care or regular meetings with palliative care clinicians (monthly as outpatients and at least twice weekly as inpatients). Among those who died (61.7%), those in the intervention group had their end-of-life preferences documented much earlier (41 days before death vs. 1.5 days, P < .001). They were also more likely to have documented end-of-life care preferences (96.5% vs. 68.4%, P < .001) and less likely to have been hospitalized within the last month of life (70.6% vs. 91.9%, P = .031). Why did this study strike you as especially important?

Dr. Kamal: A few studies have now shown better outcomes in hematology after the use of early palliative care. This has been shown not only in transplant patients but also in non-transplant patients with hematologic malignancies. As a result, you’re seeing a shift toward regular integration of palliative care.

The historical concern has been that palliative care takes the foot off the gas pedal. Another way to look at it is that palliative care helps keep the foot on the gas pedal.


Q: Should the focus be on all hematologic cancer patients or just on those who are more severe cases or whose illness is terminal?

Dr. Kamal: The focus is on patients with acute progressive leukemias rather than those with indolent, long-standing lymphomas. This a reflection of severity and complexity: In leukemia, you can be someone really sick all of a sudden and require intensive treatment.


Q: What’s new about this kind of research?

Dr. Kamal: We’re learning how palliative care is valuable in all cancers, but particularly in blood cancers, where it has historically not been studied. The groundbreaking studies in palliative care over the last 20 years have largely been in solid tumors such as lung cancers and colorectal cancers.


Q: What is unique about the patient experience in hematologic cancers compared to solid tumor cancers?

Dr. Kamal: Blood cancers are a relatively new place to integrate palliative care, but what we’re finding is that it may be even more needed than in solid tumors in terms of improving outcomes.

In pancreatic cancer, you may not know if something is going to work, but it is going to take you months to figure it out. In leukemia, there can be a lot of dynamism: You’re going to find out in a matter of days. You have to be able to pivot really quickly to the next thing, go to transplant very quickly and urgently, or make a decision to pursue supportive care.

This really compresses the normal issues like uncertainty and emotional anxiety that a pancreatic cancer patient may process over a year. Leukemic patients may need to process that over 2, 3, or 4 weeks. Palliative care can be there to help the patient to process options.


Q: You also highlighted the industry-funded phase 3 ASC4FIRST study into asciminib (Scemblix) in newly diagnosed patients with CML. The trial was led by a researcher from the South Australian Health and Medical Research Institute and the University of Adelaide, Australia. Asciminib, a STAMP inhibitor, is FDA-approved for certain CML indications. In an intention-to-treat analysis, the new study finds better major molecular response at 48 weeks for the drug vs. investigator-selected tyrosine kinase inhibitors (67.7% vs. 49.0%, P < .001). What do these findings tell you?

Dr. Kamal: CML has been a disease where you had Gleevec — imatinib — and additional options that were all in the second-line or third-line setting after failure. Now, you’re seeing durable responses across the board: an expansion of options and potentially new options in the first-line setting.

[Editor’s note: For more about asciminib, check commentaries from physicians who spoke to Medscape and ASCO Daily News.]



Q: What makes this drug unique?

Dr. Kamal: CML was the leader in helping us to understand that if you identify a mutation, you can create a medication against it. Now, what we’re finding out is that there are other ways to work around mutations. Asciminib is not affected by the most common mutations that lend to drug resistance in the classic drugs that target BCR-ABL cells like imatinib.



Q: Finally, you spotlighted a retrospective study led by researchers at Case Western Reserve University that explored rates of obesity-related cancers — including multiple myeloma — in patients with BMI ≥ 35 who took glucagon-like protein-1 receptor agonists (GLP-1 RAs) or underwent bariatric surgery. Both strategies were linked to lower risk of the cancers vs. no intervention (GLP-1 RAs, hazard ratio [HR] = 0.61; 95% CI 0.46-0.81, and bariatric surgery, HR = 0.78; 95% CI 0.67-0.91). What did you learn from this research?

Dr. Kamal: When we think about risk reduction for cancer, we generally think about hormone-driven cancers. Blood cancers are not typically hormone-driven.

This study is hinting at that idea that healthy weight across the board will reduce your cancer risk even in blood cancers, and pharmacologic interventions to reduce your weight may also reduce that cancer risk.



Q: So weight-loss drugs such as Ozempic could potentially lower the risk of hematologic cancer?

Dr. Kamal: We’re going to need more data on this, and you wouldn’t take it for that reason. But there may be a story here that says get to a healthy weight — it doesn’t matter how you do it — and your risk of all cancers goes down.

Dr. Kamal has no disclosures to report.

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

Every doctor encounters patients who complain of symptoms without identifiable physical causes. According to a recent review in The Lancet, one third of all symptoms lack somatic explanations.

How can these patients be helped, and what crucial question should always be asked? This news organization discussed this topic with Professor Peter Henningsen, a coauthor of the review, at the German Congress for Psychosomatic Medicine and Psychotherapy. Dr. Henningsen is the director of the Clinic and Polyclinic for Psychosomatic Medicine and Psychotherapy at the University Hospital Rechts der Isar of the Technical University of Munich, Munich, Germany.
 

One Common Factor

Patients often experience a wide range of symptoms that appear without any obvious cause. These symptoms include persistent pain, dizziness, cardiovascular complaints, digestive disorders, gait disturbances, exhaustion, and fatigue. There’s often a notable gap between perceived distress and the impairment of a patient’s physical functions and examination findings.

In recent years, a descriptive umbrella term has emerged for these health challenges: persistent physical symptoms. This term includes functional physical complaints lasting for months or longer without a clearly identifiable organic cause, such as chronic fatigue syndrome, irritable bowel syndrome, fibromyalgia, or multiple chemical sensitivity. It also encompasses persistent complaints in patients with an underlying condition.

According to the review, 70% of people with chronic kidney disease experience fatigue; 63% of patients with coronary artery disease have persistent pain in their arms, legs, or joints; and 31% of patients with ulcerative colitis in remission report persistent gastrointestinal symptoms.

In International Classification of Diseases (ICD), 10th Revision, the term “somatoform disorders” is used when no organic causes are identifiable. However, ICD-11 has replaced this term with the category of “somatic symptom disorders.”

“For this diagnosis, it is no longer necessary to rule out physical causes entirely,” explained Dr. Henningsen. “Instead, the focus is on psychologic and behavioral abnormalities, anxiety, increased attention to symptoms, frequent doctor consultations, and the conviction of having a serious physical illness.”

This new diagnostic approach is considered sensible because it focuses on the patient’s experience of their illness. However, it has also been criticized for potentially “psychiatrizing” patients with genuine physical ailments.
 

The ‘Prediction Machine’

Understanding the new model is crucial. “It’s about grasping what is happening with a person who persistently complains of physical symptoms,” said Dr. Henningsen.

Previously, the bottom-up model of perception, which started from the pain stimulus, was widely accepted. It was believed that pain could secondarily cause psychological symptoms. However, the role of the brain has now come to the forefront. Terms like “predictive processing” or “predictive coding” are key: The brain constantly makes predictions about the most likely interpretation of sensory impressions.

These predictions incorporate expectations, beliefs, and past experiences with symptoms, which unconsciously influence these predictions. Therefore, expectations play a role in perception for all patients regardless of whether they have an organic precondition. This phenomenon can result in patients experiencing symptoms despite minimal or no sensory input.

“Perception is always biopsychosocial,” Dr. Henningsen emphasized, and diseases are not strictly physical or psychological but rather a combination of both. The proportions of these components vary, especially in chronic illnesses, where expectations play a more significant role in pain perception than they do in fresh injuries. Because predictive processing is a general mechanism of perception, it can be involved in various diseases.

The good news is that many factors contributing to persistent physical symptoms, such as increased attention to symptoms, dysfunctional expectations, or avoidance behavior, can be positively influenced.
 

What Can Doctors Do?

Dr. Henningsen recommended that doctors treating patients with functional physical complaints focus on the following three key aspects:

• Consider the subjective experience. “The psychologic aspect is relevant in every illness. Always ask, ‘How are you coping with your symptoms? What are your expectations for the future?’ ” Dr. Henningsen explained. For instance, if a patient has been experiencing back pain for weeks, feels it’s getting worse, and believes that they will no longer be able to work, this is a significant prognostic factor. Such a patient is less likely to return to work compared with someone who is confident in their recovery.
• Communicate mindfully. The way doctors communicate with patients about their symptoms is crucial. Dr. Henningsen illustrated this with a patient with tension headaches. “An MRI might show a slight increase in signal intensity. If the doctor casually says, ‘It could be MS, but I don’t think so,’ the patient will fixate on the mention of MS.”
• Treat body and mind. There is no either-or in therapy. For example, medications can help with irritable bowel syndrome but so can psychotherapeutic measures — without implying that the condition is purely psychological. Exercise therapy can demonstrate that pain does not increase with movement, thus positively changing a patient’s expectations and reducing symptoms.

A Doctor’s ‘Toolbox’

A Norwegian study published last year in eClinicalMedicine, a Lancet journal, demonstrated the effectiveness of such an approach for treating medically unexplained physical symptoms (MUPS) in general practice.

In this study, 541 patients with MUPS participated in a two-arm, cluster-randomized trial. In total, 10 clusters of 103 general practitioners were each divided into two groups. One group used the Individual Challenge Inventory Tool (ICIT) for 11 weeks, while the other received usual treatment.

The ICIT, a structured communication tool based on cognitive-behavioral therapy, was developed by the study’s lead author, a general practitioner. Participating general practitioners were trained in using the ICIT.

Patients in the study received two or more sessions with their general practitioners. Outcomes were assessed individually, and the primary outcome was patient-reported change in function, symptoms, and quality of life as measured by the Patient Global Impression of Change. Secondary end points included work capability.

In the intervention group, 76% (n = 223) experienced significant overall improvement in function, symptoms, and the quality of life compared with 38% (n = 236) in the control group receiving usual care (mean difference, −0.8; 95% confidence interval [CI], −1.0 to −0.6; P < .0001).

After 11 weeks, sick leave decreased by 27 percentage points in the intervention group (from 52.0 to 25.2), while it dropped by only four percentage points in the usual care group (from 49.7 to 45.7).

“ICIT in primary care led to significant improvements in treatment outcomes and a reduction in sickness absence for patients with MUPS,” the authors concluded.
 

Guideline Under Revision

Medications alone often fail to adequately alleviate persistent physical symptoms. The S3 guideline “Functional Physical Complaints” lists various alternative therapies such as yoga and psychological interventions.

Dr. Henningsen and his team are revising this guideline, and publication is expected later this year. While no major changes in therapy recommendations are anticipated, the focus will be on making the guideline more user-friendly.

“It is crucial for doctors to consider psychosocial factors,” said Dr. Henningsen. “ ‘Both-and’ instead of ‘either-or’ is our motto.”

Dr. Henningsen declared no conflicts of interest.

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

A version of this article appeared on Medscape.com.

Concerned about your patient’s type 2 diabetes risk? Along with the usual preventive strategies — like diet and exercise and, when appropriate, glucagon-like peptide 1 (GLP-1) agonists — there’s another simple, no-risk strategy that just might help: Turning off the light at night.

A study in The Lancet found that people who were exposed to the most light between 12:30 a.m. and 6 a.m. were 1.5 times more likely to develop diabetes than those who remained in darkness during that time frame.

The study builds on growing evidence linking nighttime light exposure to type 2 diabetes risk. But unlike previous large studies that relied on satellite data of outdoor light levels (an indirect measure of light exposure), the recent study looked at personal light exposure — that is, light measured directly on individuals — as recorded by a wrist-worn sensor.

“Those previous studies likely underestimated the effect,” said study author Andrew Phillips, PhD, professor of sleep health at Flinders University in Adelaide, Australia, “since they did not capture indoor light environments.”

Using data from 85,000 participants from the UK Biobank, the recent study is the largest to date linking diabetes risk to personal light exposure at night.

“This is really a phenomenal study,” said Courtney Peterson, PhD, a scientist at the University of Alabama at Birmingham’s Diabetes Research Center, who was not involved in the study. “This is the first large-scale study we have looking at people’s light exposure patterns and linking it to their long-term health.”
 

What the Study Showed

The participants wore the light sensors for a week, recording day and night light from all sources — whether from sunlight, lamps, streetlights, or digital screens. The researchers then tracked participants for 8 years.

“About half of the people that we looked at had very dim levels of light at night, so less than 1 lux — that basically means less than candlelight,” said Dr. Phillips. “They were the people who were protected against type 2 diabetes.”

Those exposed to more light at night — defined in the study as 12:30 a.m.–6 a.m. — had a higher risk for type 2 diabetes. The risk went up as a dose response, Phillips said: The brighter the light exposure, the higher the diabetes risk.

Participants in the top 10% of light exposure — who were exposed to about 48 lux , or the equivalent of relatively dim overhead lighting — were 1.5 times more likely to develop diabetes than those in the dark. That’s about the risk increase you’d get from having a family history of type 2 diabetes, the researchers said.

Even when they controlled for factors like socioeconomic status, smoking, diet, exercise, and shift work, “we still found there was this very strong relationship between light exposure and risk of type 2 diabetes,” said Dr. Phillips.
 

How Light at Night May Increase Diabetes Risk

The results are not entirely surprising, said endocrinologist Susanne Miedlich, MD, a professor at the University of Rochester Medical Center, Rochester, New York, who was not involved in the study.

Light at night can disrupt the circadian rhythm, or your body’s internal 24-hour cycle. And scientists have long known that circadian rhythm is important for all kinds of biologic processes, including how the body manages blood sugar.

One’s internal clock regulates food intake, sugar absorption, and the release of insulin. Dysregulation in the circadian rhythm is associated with insulin resistance, a precursor to type 2 diabetes.

Dr. Phillips speculated that the sleep hormone melatonin also plays a role.

“Melatonin does a lot of things, but one of the things that it does is it manages our glucose and our insulin responses,” Dr. Phillips said. “So if you’re chronically getting light exposure at night, that’s reducing a level of melatonin that, in the long term, could lead to poor metabolic outcomes.”

Previous studies have explored melatonin supplementation to help manage diabetes. “However, while melatonin clearly regulates circadian rhythms, its utility as a drug to prevent diabetes has not really panned out thus far,” Dr. Miedlich said.
 

Takeaways

Interventional studies are needed to confirm whether strategies like powering down screens, turning off lights, or using blackout curtains could reduce diabetes risk.

That said, “there’s no reason not to tell people to get healthy light exposure patterns and sleep, especially in the context of diabetes,” said Dr. Phillips.

Other known strategies for reducing diabetes risk include intensive lifestyle programs, which reduce risk by up to 58%, and GLP-1 agonists.

“Probably a GLP-1 agonist is going to be more effective,” Dr. Peterson said. “But this is still a fairly large effect without having to go through the expense of buying a GLP-1 or losing a lot of weight or making a big lifestyle change.”

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

Concerned about your patient’s type 2 diabetes risk? Along with the usual preventive strategies — like diet and exercise and, when appropriate, glucagon-like peptide 1 (GLP-1) agonists — there’s another simple, no-risk strategy that just might help: Turning off the light at night.

A study in The Lancet found that people who were exposed to the most light between 12:30 a.m. and 6 a.m. were 1.5 times more likely to develop diabetes than those who remained in darkness during that time frame.

The study builds on growing evidence linking nighttime light exposure to type 2 diabetes risk. But unlike previous large studies that relied on satellite data of outdoor light levels (an indirect measure of light exposure), the recent study looked at personal light exposure — that is, light measured directly on individuals — as recorded by a wrist-worn sensor.

“Those previous studies likely underestimated the effect,” said study author Andrew Phillips, PhD, professor of sleep health at Flinders University in Adelaide, Australia, “since they did not capture indoor light environments.”

Using data from 85,000 participants from the UK Biobank, the recent study is the largest to date linking diabetes risk to personal light exposure at night.

“This is really a phenomenal study,” said Courtney Peterson, PhD, a scientist at the University of Alabama at Birmingham’s Diabetes Research Center, who was not involved in the study. “This is the first large-scale study we have looking at people’s light exposure patterns and linking it to their long-term health.”
 

What the Study Showed

The participants wore the light sensors for a week, recording day and night light from all sources — whether from sunlight, lamps, streetlights, or digital screens. The researchers then tracked participants for 8 years.

“About half of the people that we looked at had very dim levels of light at night, so less than 1 lux — that basically means less than candlelight,” said Dr. Phillips. “They were the people who were protected against type 2 diabetes.”

Those exposed to more light at night — defined in the study as 12:30 a.m.–6 a.m. — had a higher risk for type 2 diabetes. The risk went up as a dose response, Phillips said: The brighter the light exposure, the higher the diabetes risk.

Participants in the top 10% of light exposure — who were exposed to about 48 lux , or the equivalent of relatively dim overhead lighting — were 1.5 times more likely to develop diabetes than those in the dark. That’s about the risk increase you’d get from having a family history of type 2 diabetes, the researchers said.

Even when they controlled for factors like socioeconomic status, smoking, diet, exercise, and shift work, “we still found there was this very strong relationship between light exposure and risk of type 2 diabetes,” said Dr. Phillips.
 

How Light at Night May Increase Diabetes Risk

The results are not entirely surprising, said endocrinologist Susanne Miedlich, MD, a professor at the University of Rochester Medical Center, Rochester, New York, who was not involved in the study.

Light at night can disrupt the circadian rhythm, or your body’s internal 24-hour cycle. And scientists have long known that circadian rhythm is important for all kinds of biologic processes, including how the body manages blood sugar.

One’s internal clock regulates food intake, sugar absorption, and the release of insulin. Dysregulation in the circadian rhythm is associated with insulin resistance, a precursor to type 2 diabetes.

Dr. Phillips speculated that the sleep hormone melatonin also plays a role.

“Melatonin does a lot of things, but one of the things that it does is it manages our glucose and our insulin responses,” Dr. Phillips said. “So if you’re chronically getting light exposure at night, that’s reducing a level of melatonin that, in the long term, could lead to poor metabolic outcomes.”

Previous studies have explored melatonin supplementation to help manage diabetes. “However, while melatonin clearly regulates circadian rhythms, its utility as a drug to prevent diabetes has not really panned out thus far,” Dr. Miedlich said.
 

Takeaways

Interventional studies are needed to confirm whether strategies like powering down screens, turning off lights, or using blackout curtains could reduce diabetes risk.

That said, “there’s no reason not to tell people to get healthy light exposure patterns and sleep, especially in the context of diabetes,” said Dr. Phillips.

Other known strategies for reducing diabetes risk include intensive lifestyle programs, which reduce risk by up to 58%, and GLP-1 agonists.

“Probably a GLP-1 agonist is going to be more effective,” Dr. Peterson said. “But this is still a fairly large effect without having to go through the expense of buying a GLP-1 or losing a lot of weight or making a big lifestyle change.”

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

Concerned about your patient’s type 2 diabetes risk? Along with the usual preventive strategies — like diet and exercise and, when appropriate, glucagon-like peptide 1 (GLP-1) agonists — there’s another simple, no-risk strategy that just might help: Turning off the light at night.

A study in The Lancet found that people who were exposed to the most light between 12:30 a.m. and 6 a.m. were 1.5 times more likely to develop diabetes than those who remained in darkness during that time frame.

The study builds on growing evidence linking nighttime light exposure to type 2 diabetes risk. But unlike previous large studies that relied on satellite data of outdoor light levels (an indirect measure of light exposure), the recent study looked at personal light exposure — that is, light measured directly on individuals — as recorded by a wrist-worn sensor.

“Those previous studies likely underestimated the effect,” said study author Andrew Phillips, PhD, professor of sleep health at Flinders University in Adelaide, Australia, “since they did not capture indoor light environments.”

Using data from 85,000 participants from the UK Biobank, the recent study is the largest to date linking diabetes risk to personal light exposure at night.

“This is really a phenomenal study,” said Courtney Peterson, PhD, a scientist at the University of Alabama at Birmingham’s Diabetes Research Center, who was not involved in the study. “This is the first large-scale study we have looking at people’s light exposure patterns and linking it to their long-term health.”
 

What the Study Showed

The participants wore the light sensors for a week, recording day and night light from all sources — whether from sunlight, lamps, streetlights, or digital screens. The researchers then tracked participants for 8 years.

“About half of the people that we looked at had very dim levels of light at night, so less than 1 lux — that basically means less than candlelight,” said Dr. Phillips. “They were the people who were protected against type 2 diabetes.”

Those exposed to more light at night — defined in the study as 12:30 a.m.–6 a.m. — had a higher risk for type 2 diabetes. The risk went up as a dose response, Phillips said: The brighter the light exposure, the higher the diabetes risk.

Participants in the top 10% of light exposure — who were exposed to about 48 lux , or the equivalent of relatively dim overhead lighting — were 1.5 times more likely to develop diabetes than those in the dark. That’s about the risk increase you’d get from having a family history of type 2 diabetes, the researchers said.

Even when they controlled for factors like socioeconomic status, smoking, diet, exercise, and shift work, “we still found there was this very strong relationship between light exposure and risk of type 2 diabetes,” said Dr. Phillips.
 

How Light at Night May Increase Diabetes Risk

The results are not entirely surprising, said endocrinologist Susanne Miedlich, MD, a professor at the University of Rochester Medical Center, Rochester, New York, who was not involved in the study.

Light at night can disrupt the circadian rhythm, or your body’s internal 24-hour cycle. And scientists have long known that circadian rhythm is important for all kinds of biologic processes, including how the body manages blood sugar.

One’s internal clock regulates food intake, sugar absorption, and the release of insulin. Dysregulation in the circadian rhythm is associated with insulin resistance, a precursor to type 2 diabetes.

Dr. Phillips speculated that the sleep hormone melatonin also plays a role.

“Melatonin does a lot of things, but one of the things that it does is it manages our glucose and our insulin responses,” Dr. Phillips said. “So if you’re chronically getting light exposure at night, that’s reducing a level of melatonin that, in the long term, could lead to poor metabolic outcomes.”

Previous studies have explored melatonin supplementation to help manage diabetes. “However, while melatonin clearly regulates circadian rhythms, its utility as a drug to prevent diabetes has not really panned out thus far,” Dr. Miedlich said.
 

Takeaways

Interventional studies are needed to confirm whether strategies like powering down screens, turning off lights, or using blackout curtains could reduce diabetes risk.

That said, “there’s no reason not to tell people to get healthy light exposure patterns and sleep, especially in the context of diabetes,” said Dr. Phillips.

Other known strategies for reducing diabetes risk include intensive lifestyle programs, which reduce risk by up to 58%, and GLP-1 agonists.

“Probably a GLP-1 agonist is going to be more effective,” Dr. Peterson said. “But this is still a fairly large effect without having to go through the expense of buying a GLP-1 or losing a lot of weight or making a big lifestyle change.”

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

Federal officials on July 11 proposed Medicare rates that effectively would cut physician pay by about 3% in 2025, touching off a fresh round of protests from medical associations.

The 2025 draft base rate, or conversion factor, is slated to drop to $32.36 from the current level of $33.29, the Centers for Medicare & Medicaid Services said.

The American Medical Association (AMA), the American Academy of Family Physicians (AAFP) and other groups on July 10 reiterated calls on Congress to revise the law on Medicare payment for physicians and move away from short-term tweaks.

This proposed cut is mostly due to the 5-year freeze in the physician schedule base rate mandated by the 2015 Medicare Access and CHIP Reauthorization Act (MACRA). Congress designed MACRA with an aim of shifting clinicians toward programs that would peg pay increases to quality measures.

Lawmakers have since had to soften the blow of that freeze, acknowledging flaws in MACRA and inflation’s significant toll on medical practices. Yet lawmakers have made temporary fixes, such as a 2.93% increase in current payment that’s set to expire.

“Previous quick fixes have been insufficient — this situation requires a bold, substantial approach,” Bruce A. Scott, MD, the AMA president, said in a statement. “A Band-Aid goes only so far when the patient is in dire need.”

Dr. Scott noted that the Medicare Economic Index — a measure of practice cost inflation — is expected to rise by 3.6% in 2025.

“As a first step, Congress must enact an annual inflationary update to help physician payment rates keep pace with rising practice costs,” Steven P. Furr, MD, AAFP’s president, said in a statement released July 10. “Any payment reductions will threaten practices and exacerbate workforce shortages, preventing patients from accessing the primary care, behavioral health care, and other critical preventive services they need.”

Many medical groups, including the AMA, AAFP, and the Medical Group Management Association, are pressing Congress to pass a law that would tie the conversion factor of the physician fee schedule to inflation.

Influential advisory groups also have backed the idea of increasing the conversion factor. For example, the Medicare Payment Advisory Commission in March recommended to Congress that it increase the 2025 conversion factor, suggesting a bump of half of the projected increase in the Medicare Economic Index.

Congress seems unlikely to revamp the physician fee schedule this year, with members spending significant time away from Washington ahead of the November election.

That could make it likely that Congress’ next action on Medicare payment rates would be another short-term tweak — instead of long-lasting change.

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

Federal officials on July 11 proposed Medicare rates that effectively would cut physician pay by about 3% in 2025, touching off a fresh round of protests from medical associations.

The 2025 draft base rate, or conversion factor, is slated to drop to $32.36 from the current level of $33.29, the Centers for Medicare & Medicaid Services said.

The American Medical Association (AMA), the American Academy of Family Physicians (AAFP) and other groups on July 10 reiterated calls on Congress to revise the law on Medicare payment for physicians and move away from short-term tweaks.

This proposed cut is mostly due to the 5-year freeze in the physician schedule base rate mandated by the 2015 Medicare Access and CHIP Reauthorization Act (MACRA). Congress designed MACRA with an aim of shifting clinicians toward programs that would peg pay increases to quality measures.

Lawmakers have since had to soften the blow of that freeze, acknowledging flaws in MACRA and inflation’s significant toll on medical practices. Yet lawmakers have made temporary fixes, such as a 2.93% increase in current payment that’s set to expire.

“Previous quick fixes have been insufficient — this situation requires a bold, substantial approach,” Bruce A. Scott, MD, the AMA president, said in a statement. “A Band-Aid goes only so far when the patient is in dire need.”

Dr. Scott noted that the Medicare Economic Index — a measure of practice cost inflation — is expected to rise by 3.6% in 2025.

“As a first step, Congress must enact an annual inflationary update to help physician payment rates keep pace with rising practice costs,” Steven P. Furr, MD, AAFP’s president, said in a statement released July 10. “Any payment reductions will threaten practices and exacerbate workforce shortages, preventing patients from accessing the primary care, behavioral health care, and other critical preventive services they need.”

Many medical groups, including the AMA, AAFP, and the Medical Group Management Association, are pressing Congress to pass a law that would tie the conversion factor of the physician fee schedule to inflation.

Influential advisory groups also have backed the idea of increasing the conversion factor. For example, the Medicare Payment Advisory Commission in March recommended to Congress that it increase the 2025 conversion factor, suggesting a bump of half of the projected increase in the Medicare Economic Index.

Congress seems unlikely to revamp the physician fee schedule this year, with members spending significant time away from Washington ahead of the November election.

That could make it likely that Congress’ next action on Medicare payment rates would be another short-term tweak — instead of long-lasting change.

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

Federal officials on July 11 proposed Medicare rates that effectively would cut physician pay by about 3% in 2025, touching off a fresh round of protests from medical associations.

The 2025 draft base rate, or conversion factor, is slated to drop to $32.36 from the current level of $33.29, the Centers for Medicare & Medicaid Services said.

The American Medical Association (AMA), the American Academy of Family Physicians (AAFP) and other groups on July 10 reiterated calls on Congress to revise the law on Medicare payment for physicians and move away from short-term tweaks.

This proposed cut is mostly due to the 5-year freeze in the physician schedule base rate mandated by the 2015 Medicare Access and CHIP Reauthorization Act (MACRA). Congress designed MACRA with an aim of shifting clinicians toward programs that would peg pay increases to quality measures.

Lawmakers have since had to soften the blow of that freeze, acknowledging flaws in MACRA and inflation’s significant toll on medical practices. Yet lawmakers have made temporary fixes, such as a 2.93% increase in current payment that’s set to expire.

“Previous quick fixes have been insufficient — this situation requires a bold, substantial approach,” Bruce A. Scott, MD, the AMA president, said in a statement. “A Band-Aid goes only so far when the patient is in dire need.”

Dr. Scott noted that the Medicare Economic Index — a measure of practice cost inflation — is expected to rise by 3.6% in 2025.

“As a first step, Congress must enact an annual inflationary update to help physician payment rates keep pace with rising practice costs,” Steven P. Furr, MD, AAFP’s president, said in a statement released July 10. “Any payment reductions will threaten practices and exacerbate workforce shortages, preventing patients from accessing the primary care, behavioral health care, and other critical preventive services they need.”

Many medical groups, including the AMA, AAFP, and the Medical Group Management Association, are pressing Congress to pass a law that would tie the conversion factor of the physician fee schedule to inflation.

Influential advisory groups also have backed the idea of increasing the conversion factor. For example, the Medicare Payment Advisory Commission in March recommended to Congress that it increase the 2025 conversion factor, suggesting a bump of half of the projected increase in the Medicare Economic Index.

Congress seems unlikely to revamp the physician fee schedule this year, with members spending significant time away from Washington ahead of the November election.

That could make it likely that Congress’ next action on Medicare payment rates would be another short-term tweak — instead of long-lasting change.

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

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

Agitation is a neuropsychiatric symptom in patients with Alzheimer’s disease (AD), the most common form of dementia. The prevalence of this symptom is about 40%-65%, with the higher end of the range applying to patients who have moderate to severe dementia. Agitation often begins early in the course of the disease and is persistent, which contributes to increased healthcare costs and significantly increases both caregiver burden and patient distress. The DICE approach is a collaborative process for managing behavioral symptoms in dementia, wherein the caregiver describes the behaviors, the provider investigates the etiology, the provider and caregiver create a treatment plan, and the provider evaluates the outcome of the interventions. We use this widely adopted approach as the framework for discussing recent advances in the management of agitation.

Here are five things to know about managing agitation in AD.
 

1. There is a new operational definition for agitation in dementia.

Agitation in dementia is a syndrome that encompasses specific behaviors across all dementia types. The 2023 operational definition of agitation in dementia by the International Psychogeriatric Association (IPA) includes three domains: excessive motor activity (including pacing, rocking, restlessness, and performing repetitious mannerisms), verbal aggression (including using profanity, screaming, and shouting), and physical aggression (including interpersonal aggression and mishandling or destruction of property). These behaviors must be persistent or recurrent for at least 2 weeks or represent a dramatic change from the person’s baseline behavior, must be associated with excessive distress or disability beyond what is caused by the cognitive impairment itself, and result in significant impairment in at least one of the three specified functional domains. Behavioral symptoms in dementia frequently co-occur, which affects treatment and prognosis. For instance, the risk for stroke associated with antipsychotic treatments appears to be higher in dementia-related psychosis without agitation than in agitation alone or in psychosis with agitation. Therefore, the use of a rating scale such as the Neuropsychiatric Inventory–Questionnaire (NPI-Q), which takes 5 minutes or less to administer, is recommended to identify and track behavioral symptoms and caregiver distress.

2. The etiology of agitation in dementia may be multifactorial.

It is important in every case to identify all underlying etiologies so that presumed causal and/or exacerbating factors are not inadvertently missed. Agitation may be a means of communicating distress owing to unmet needs or a patient-environment mismatch (function-focused approach) or may be a direct consequence of the dementia itself (behavioral-symptom approach). These approaches are not mutually exclusive. A patient can present with agitation as a direct consequence of dementia and inadequately treated pain concurrently. 

The new IPA definition specifies several exclusion criteria for agitation in dementia, including underlying medical conditions, delirium, substance use, and suboptimal care conditions. It is especially crucial to accurately identify delirium because dementia is an independent risk factor for delirium, which in turn may accelerate the progression of cognitive and functional decline. Even subsyndromal delirium in older adults leads to a higher 3-year mortality rate that is comparable to that seen in delirium. Older adults with acute-onset agitation in the context of dementia should undergo a comprehensive assessment for delirium, as agitation may be the only indication of a serious underlying medical condition. 
 

3. Nonpharmacologic interventions should be used whenever possible. 

The wider adoption of nonpharmacologic interventions in clinical practice has been greatly limited by the heterogeneity in study protocols, including in selection of participants, in the types of dementias included, and in defining and applying the intervention strategies. Nevertheless, there is general consensus that individualized behavioral strategies that build on the patients’ interests and preserved abilities are more effective, at least in the short term. Patients best suited for these interventions are those with less cognitive decline, better communication skills, less impairment in activities of daily living, and higher responsiveness. A systematic review of systematic reviews found music therapy to be the most effective intervention for reducing agitation and aggression in dementia, along with behavioral management techniques when supervised by healthcare professionals. On the other hand, physical restraints are best avoided, as their use in hospitalized patients has been associated with longer stays, higher costs, lower odds of being discharged to home, and in long-term care patients with longer stays, with increased risk for medical complications and functional decline. 

4. Antidepressants are not all equally safe or efficacious in managing agitation.

In a network meta-analysis that looked at the effects of several antidepressants on agitation in dementia, citalopram had just under 95% probability of efficacy and was the only antidepressant that was significantly more efficacious than placebo. In the multicenter CitAD trial, citalopram was efficacious and well tolerated for the treatment of agitation in AD, but the mean dose of citalopram used, 30 mg/d, was higher than the maximum dose of 20 mg/d recommended by the US Food and Drug Administration (FDA) in those aged 60 years or above. The optimal candidates for citalopram were those under the age of 85 with mild to moderate AD and mild to moderate nonpsychotic agitation, and it took up to 9 weeks for it to be fully effective. Due to the risk for dose-dependent QTc prolongation with citalopram, a baseline ECG must be done, and a second ECG is recommended if a clinical decision is made to exceed the recommended maximum daily dose. In the CitAD trial, 66% of patients in the citalopram arm received cholinesterase inhibitors concurrently while 44% received memantine, so these symptomatic treatments for AD should not be stopped solely for initiating a citalopram trial. 

The antiagitation effect of citalopram may well be a class effect of all selective serotonin reuptake inhibitors (SSRIs), given that there is also evidence favoring the use of sertraline and escitalopram. The S-CitAD trial, the first large, randomized controlled study of escitalopram for the treatment of agitation in dementia, is expected to announce its top-line results sometime this year. However, not all antidepressant classes appear to be equally efficacious or safe. In the large, 12-week randomized placebo-controlled trial SYMBAD, mirtazapine was not only ineffective in treating nonpsychotic agitation in AD but was also associated with a higher mortality rate that just missed statistical significance. Trazodone is also often used for treating agitation, but there is insufficient evidence regarding efficacy and a high probability of adverse effects, even at low doses.
 

5. Antipsychotics may be effective drugs for treating severe dementia-related agitation.

The CATIE-AD study found that the small beneficial effects of antipsychotics for treating agitation and psychosis in AD were offset by their adverse effects and high discontinuation rates, and the FDA-imposed boxed warnings in 2005 and 2008 cautioned against the use of both first- and second-generation antipsychotics to manage dementia-related psychosis owing to an increased risk for death. Subsequently, the quest for safer and more effective alternatives culminated in the FDA approval of brexpiprazole in 2023 for the treatment of agitation in AD, but the black box warning was left in place. Three randomized controlled trials found brexpiprazole to be relatively safe, with statistically significant improvement in agitation. It was especially efficacious for severe agitation, but there is controversy about whether such improvement is clinically meaningful and whether brexpiprazole is truly superior to other antipsychotics for treating dementia-related agitation. As in the previously mentioned citalopram studies, most patients in the brexpiprazole studies received the drug as an add-on to memantine and/or a cholinesterase inhibitor, and it was proven effective over a period of up to 12 weeks across the three trials. Regarding other antipsychotics, aripiprazole and risperidone have been shown to be effective in treating agitation in patients with mixed dementia, but risperidone has also been associated with the highest risk for strokes (about 80% probability). Unfortunately, an unintended consequence of the boxed warnings on antipsychotics has been an increase in off-label substitution of psychotropic drugs with unproven efficacy and a questionable safety profile, such as valproic acid preparations, that have been linked to an increased short-term risk for accelerated brain volume loss and rapid cognitive decline, as well as a higher risk for mortality.

Lisa M. Wise, assistant professor, Psychiatry, at Oregon Health & Science University, and staff psychiatrist, Department of Psychiatry, Portland VA Medical Center, Portland, Oregon, and Vimal M. Aga, adjunct assistant professor, Department of Neurology, Oregon Health & Science University, and geriatric psychiatrist, Layton Aging and Alzheimer’s Disease Center, Portland, Oregon, have disclosed no relevant financial relationships.

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

MILAN — Liver transplantation improves survival in patients with acute-on-chronic liver failure (ACLF), according to interim clinical outcomes of the large, international CHANCE study.

To date, the results show that 3-month post–liver transplantation mortality rates in patients with ACLF grades 2 and 3 were only 9%, which is not significantly different than that of patients with decompensated cirrhosis, with a mortality of 7%.

University College London Hospitals

“Treatment of ACLF is an unmet medical need,” said Rajiv Jalan, MD, professor of hepatology and honorary consultant in hepatology, University College London Hospitals, London, England.

These findings highlight “the inadequacy of current transplant allocation criteria for patients with ACLF 2 and 3,” which is leading to excess mortality on the wait list, he added.

Dr. Jalan presented the interim results at the European Association for the Study of the Liver (EASL) Congress 2024.

If confirmed in the full analysis, these results argue strongly for increasing access to liver transplantation and changing organ allocation for patients with ACLF 2 and 3, he said.
 

Organ Allocation Principally Based on MELD Scores

ACLF, which occurs in patients with cirrhosis and acutely decompensated liver disease admitted to hospital, carries a high, short-term risk for death. The risk for 28-day mortality for ACLF 2 and 3 is between 30% and 90% and characterized by multiorgan failure.

As seen in previous data, even patients on the transplant waiting list with a low Model for End-Stage Liver Disease (MELD) score have a risk for death between 20% and 30% if they are ACLF 2 and 3, Dr. Jalan said.

MELD scores do not consider the risk for death because of failure of extrahepatic organs, he added. Existing worldwide organ allocation systems are principally based on patient MELD scores or its variations; therefore, many patients die on the waiting list.

With this in mind, the CHANCE study aimed to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF 2 or 3 at the time of transplantation with patients with decompensated cirrhosis without ACLF and transplantation-free survival of patients with ACLF 2 or 3 not listed for liver transplantation.

The multicenter observational study comprised 66 liver transplant centers from 21 countries and over 500 investigators. Recruitment was closed after 1000 patients were enrolled.

Patients were aged 54-56 years, 31%-35% were women, 48%-70% had alcohol-related cirrhosis, and 19%-24% had metabolic dysfunction–associated steatohepatitis. MELD scores ranged from 25 to 36.

For the interim results, Dr. Jalan and colleagues assessed mortality on the waiting list and 3-month post–liver transplantation mortality.

Secondary endpoints included quality of life and cost of care.

Of the 823 patients in the study, they were grouped as follows: 376 patients with ACLF 2 or 3 listed for liver transplantation (group 1), 313 patients with ACLF 0 or 1 and MELD score > 20 listed for liver transplantation (group 2), and 134 patients with ACLF 2 or 3 not listed for liver transplantation (group 3).

Overall, patients in group 1 had very severe ACLF; 177 patients with ACLF 3 had three or more organ failures, Dr. Jalan noted.

“It is interesting to note that, in group 3, there is an overrepresentation of alcohol-related cirrhosis, and this might reflect a bias in transplantation,” he added.

Dr. Jalan highlighted geographical points of difference. Patients in the United States were younger, which could be important when interpreting results of post-transplantation outcomes. In Asia, the majority of the patients were men and primarily from India, where living donor transplantation is commonly performed. In Latin America, only 33% of study participants had alcohol-related cirrhosis in contrast to 67% of those in North America.

However, “comorbidities across the world were similar, and MELD scores were also similar,” Dr. Jalan said.
 

Death or Delisting

Between listing and transplantation, 28% of patients in group 1 either died or were delisted, compared with 16% of those in group 2. In group 3, 85% of patients who were not listed for transplantation in the first place died.

Similar to what has been seen in other studies, nearly 50% of patients with ACLF 3 but a MELD score < 25 on the wait list died or were delisted, Dr. Jalan pointed out, suggesting that these patients are disadvantaged under the current system of waiting list priority.

Geographically, deaths on the wait list were significantly higher in Latin America at 40% than in North America, Europe, and Asia at 20%, 18%, and 13%, respectively.

“This is likely due to low donation rates in Latin America,” Dr. Jalan said.

Turning to 3-month post-transplantation mortality, the rates in groups 1 and 2 were 9% and 7%, respectively.

“This demonstrates very nicely the clear benefit of transplant,” Dr. Jalan said. “The risk of death post transplant, even with ACLF 2 or 3, is not significantly different to those patients with decompensated cirrhosis.”

There was a slightly higher risk for death in patients with ACLF 3 than in those with ACLF 2 at 14% vs 7%, but “the risk of death in these patients if they don’t have transportation is 70%-80%,” he said.

Looking at 3-month post-transplantation mortality by continent, Dr. Jalan highlighted that Latin America showed 16% risk, compared with Asia, Europe, and North America that showed 12%, 7%, and 3% risk, respectively.

“This is probably multifactorial and likely to be influenced by time on the waiting list, quality of organs available, and patient demographics, among other factors,” Dr. Jalan said. When very sick people undergo transplantation, “there is a higher risk of death.”

The patients in this study have waited a long time, “which worsens their situation,” said Dr. Jalan, reinforcing his argument for changing the international organ allocation system to allow earlier access for these patients.
 

‘The Landscape of Organ Allocation Is Extremely Complex’

Comoderator Ana Lleo, MD, PhD, full professor of internal medicine and hepatology, Humanitas University, Milan, Italy, commented that “the number of patients included in this international study is significant,” and that the issue of mortality on the wait list is of great clinical interest.

“The landscape of organ allocation is extremely complex,” she added.

The system for liver transplantation considers a large number of clinical conditions with very diverse benefit profiles, she explained.

“While we would like to offer liver transplantation for all patients with any range of benefit, the current donations are not sufficient to cover the request,” Dr. Lleo said. “Therefore, prioritization remains key.”

The findings do illustrate the inadequacy of current transplantation allocation criteria for patients with ACLF 2 and 3, said Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College Hospital, London, England, who is also serving as vice-secretary of the EASL Governing Board.

However, “this must be balanced by the recognition that the global donor pool of organs available is a finite resource,” she said, echoing Dr. Lleo’s comments.

This calls for wider ethical discussions to avoid disadvantaging more stable, often younger patients with cirrhosis who are listed for transplantation, she added.

Dr. Jalan declared he is the inventor of Ornithine Phenylacetate, licensed by UCL to Mallinckrodt Pharma; a speaker and grant reviewer for Grifols Research Collaboration: Yaqrit; and the founder of Yaqrit, Hepyx, CyberLiver, and Gigabiome. Dr. Lleo declared that she does not have any conflicts relevant to this work but received lecture fees from Gilead, Advanz Pharma, Alfasigma, GSK, Incyte, Gore, AstraZeneca, and Ipsen and consulted for Advanz Pharma, AstraZeneca, Ipsen, GSK, and Dr Falk. Dr. Shawcross declared advisory board/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.

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

MILAN — Liver transplantation improves survival in patients with acute-on-chronic liver failure (ACLF), according to interim clinical outcomes of the large, international CHANCE study.

To date, the results show that 3-month post–liver transplantation mortality rates in patients with ACLF grades 2 and 3 were only 9%, which is not significantly different than that of patients with decompensated cirrhosis, with a mortality of 7%.

University College London Hospitals

“Treatment of ACLF is an unmet medical need,” said Rajiv Jalan, MD, professor of hepatology and honorary consultant in hepatology, University College London Hospitals, London, England.

These findings highlight “the inadequacy of current transplant allocation criteria for patients with ACLF 2 and 3,” which is leading to excess mortality on the wait list, he added.

Dr. Jalan presented the interim results at the European Association for the Study of the Liver (EASL) Congress 2024.

If confirmed in the full analysis, these results argue strongly for increasing access to liver transplantation and changing organ allocation for patients with ACLF 2 and 3, he said.
 

Organ Allocation Principally Based on MELD Scores

ACLF, which occurs in patients with cirrhosis and acutely decompensated liver disease admitted to hospital, carries a high, short-term risk for death. The risk for 28-day mortality for ACLF 2 and 3 is between 30% and 90% and characterized by multiorgan failure.

As seen in previous data, even patients on the transplant waiting list with a low Model for End-Stage Liver Disease (MELD) score have a risk for death between 20% and 30% if they are ACLF 2 and 3, Dr. Jalan said.

MELD scores do not consider the risk for death because of failure of extrahepatic organs, he added. Existing worldwide organ allocation systems are principally based on patient MELD scores or its variations; therefore, many patients die on the waiting list.

With this in mind, the CHANCE study aimed to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF 2 or 3 at the time of transplantation with patients with decompensated cirrhosis without ACLF and transplantation-free survival of patients with ACLF 2 or 3 not listed for liver transplantation.

The multicenter observational study comprised 66 liver transplant centers from 21 countries and over 500 investigators. Recruitment was closed after 1000 patients were enrolled.

Patients were aged 54-56 years, 31%-35% were women, 48%-70% had alcohol-related cirrhosis, and 19%-24% had metabolic dysfunction–associated steatohepatitis. MELD scores ranged from 25 to 36.

For the interim results, Dr. Jalan and colleagues assessed mortality on the waiting list and 3-month post–liver transplantation mortality.

Secondary endpoints included quality of life and cost of care.

Of the 823 patients in the study, they were grouped as follows: 376 patients with ACLF 2 or 3 listed for liver transplantation (group 1), 313 patients with ACLF 0 or 1 and MELD score > 20 listed for liver transplantation (group 2), and 134 patients with ACLF 2 or 3 not listed for liver transplantation (group 3).

Overall, patients in group 1 had very severe ACLF; 177 patients with ACLF 3 had three or more organ failures, Dr. Jalan noted.

“It is interesting to note that, in group 3, there is an overrepresentation of alcohol-related cirrhosis, and this might reflect a bias in transplantation,” he added.

Dr. Jalan highlighted geographical points of difference. Patients in the United States were younger, which could be important when interpreting results of post-transplantation outcomes. In Asia, the majority of the patients were men and primarily from India, where living donor transplantation is commonly performed. In Latin America, only 33% of study participants had alcohol-related cirrhosis in contrast to 67% of those in North America.

However, “comorbidities across the world were similar, and MELD scores were also similar,” Dr. Jalan said.
 

Death or Delisting

Between listing and transplantation, 28% of patients in group 1 either died or were delisted, compared with 16% of those in group 2. In group 3, 85% of patients who were not listed for transplantation in the first place died.

Similar to what has been seen in other studies, nearly 50% of patients with ACLF 3 but a MELD score < 25 on the wait list died or were delisted, Dr. Jalan pointed out, suggesting that these patients are disadvantaged under the current system of waiting list priority.

Geographically, deaths on the wait list were significantly higher in Latin America at 40% than in North America, Europe, and Asia at 20%, 18%, and 13%, respectively.

“This is likely due to low donation rates in Latin America,” Dr. Jalan said.

Turning to 3-month post-transplantation mortality, the rates in groups 1 and 2 were 9% and 7%, respectively.

“This demonstrates very nicely the clear benefit of transplant,” Dr. Jalan said. “The risk of death post transplant, even with ACLF 2 or 3, is not significantly different to those patients with decompensated cirrhosis.”

There was a slightly higher risk for death in patients with ACLF 3 than in those with ACLF 2 at 14% vs 7%, but “the risk of death in these patients if they don’t have transportation is 70%-80%,” he said.

Looking at 3-month post-transplantation mortality by continent, Dr. Jalan highlighted that Latin America showed 16% risk, compared with Asia, Europe, and North America that showed 12%, 7%, and 3% risk, respectively.

“This is probably multifactorial and likely to be influenced by time on the waiting list, quality of organs available, and patient demographics, among other factors,” Dr. Jalan said. When very sick people undergo transplantation, “there is a higher risk of death.”

The patients in this study have waited a long time, “which worsens their situation,” said Dr. Jalan, reinforcing his argument for changing the international organ allocation system to allow earlier access for these patients.
 

‘The Landscape of Organ Allocation Is Extremely Complex’

Comoderator Ana Lleo, MD, PhD, full professor of internal medicine and hepatology, Humanitas University, Milan, Italy, commented that “the number of patients included in this international study is significant,” and that the issue of mortality on the wait list is of great clinical interest.

“The landscape of organ allocation is extremely complex,” she added.

The system for liver transplantation considers a large number of clinical conditions with very diverse benefit profiles, she explained.

“While we would like to offer liver transplantation for all patients with any range of benefit, the current donations are not sufficient to cover the request,” Dr. Lleo said. “Therefore, prioritization remains key.”

The findings do illustrate the inadequacy of current transplantation allocation criteria for patients with ACLF 2 and 3, said Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College Hospital, London, England, who is also serving as vice-secretary of the EASL Governing Board.

However, “this must be balanced by the recognition that the global donor pool of organs available is a finite resource,” she said, echoing Dr. Lleo’s comments.

This calls for wider ethical discussions to avoid disadvantaging more stable, often younger patients with cirrhosis who are listed for transplantation, she added.

Dr. Jalan declared he is the inventor of Ornithine Phenylacetate, licensed by UCL to Mallinckrodt Pharma; a speaker and grant reviewer for Grifols Research Collaboration: Yaqrit; and the founder of Yaqrit, Hepyx, CyberLiver, and Gigabiome. Dr. Lleo declared that she does not have any conflicts relevant to this work but received lecture fees from Gilead, Advanz Pharma, Alfasigma, GSK, Incyte, Gore, AstraZeneca, and Ipsen and consulted for Advanz Pharma, AstraZeneca, Ipsen, GSK, and Dr Falk. Dr. Shawcross declared advisory board/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.

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

MILAN — Liver transplantation improves survival in patients with acute-on-chronic liver failure (ACLF), according to interim clinical outcomes of the large, international CHANCE study.

To date, the results show that 3-month post–liver transplantation mortality rates in patients with ACLF grades 2 and 3 were only 9%, which is not significantly different than that of patients with decompensated cirrhosis, with a mortality of 7%.

University College London Hospitals

“Treatment of ACLF is an unmet medical need,” said Rajiv Jalan, MD, professor of hepatology and honorary consultant in hepatology, University College London Hospitals, London, England.

These findings highlight “the inadequacy of current transplant allocation criteria for patients with ACLF 2 and 3,” which is leading to excess mortality on the wait list, he added.

Dr. Jalan presented the interim results at the European Association for the Study of the Liver (EASL) Congress 2024.

If confirmed in the full analysis, these results argue strongly for increasing access to liver transplantation and changing organ allocation for patients with ACLF 2 and 3, he said.
 

Organ Allocation Principally Based on MELD Scores

ACLF, which occurs in patients with cirrhosis and acutely decompensated liver disease admitted to hospital, carries a high, short-term risk for death. The risk for 28-day mortality for ACLF 2 and 3 is between 30% and 90% and characterized by multiorgan failure.

As seen in previous data, even patients on the transplant waiting list with a low Model for End-Stage Liver Disease (MELD) score have a risk for death between 20% and 30% if they are ACLF 2 and 3, Dr. Jalan said.

MELD scores do not consider the risk for death because of failure of extrahepatic organs, he added. Existing worldwide organ allocation systems are principally based on patient MELD scores or its variations; therefore, many patients die on the waiting list.

With this in mind, the CHANCE study aimed to compare 1-year graft and patient survival rates after liver transplantation in patients with ACLF 2 or 3 at the time of transplantation with patients with decompensated cirrhosis without ACLF and transplantation-free survival of patients with ACLF 2 or 3 not listed for liver transplantation.

The multicenter observational study comprised 66 liver transplant centers from 21 countries and over 500 investigators. Recruitment was closed after 1000 patients were enrolled.

Patients were aged 54-56 years, 31%-35% were women, 48%-70% had alcohol-related cirrhosis, and 19%-24% had metabolic dysfunction–associated steatohepatitis. MELD scores ranged from 25 to 36.

For the interim results, Dr. Jalan and colleagues assessed mortality on the waiting list and 3-month post–liver transplantation mortality.

Secondary endpoints included quality of life and cost of care.

Of the 823 patients in the study, they were grouped as follows: 376 patients with ACLF 2 or 3 listed for liver transplantation (group 1), 313 patients with ACLF 0 or 1 and MELD score > 20 listed for liver transplantation (group 2), and 134 patients with ACLF 2 or 3 not listed for liver transplantation (group 3).

Overall, patients in group 1 had very severe ACLF; 177 patients with ACLF 3 had three or more organ failures, Dr. Jalan noted.

“It is interesting to note that, in group 3, there is an overrepresentation of alcohol-related cirrhosis, and this might reflect a bias in transplantation,” he added.

Dr. Jalan highlighted geographical points of difference. Patients in the United States were younger, which could be important when interpreting results of post-transplantation outcomes. In Asia, the majority of the patients were men and primarily from India, where living donor transplantation is commonly performed. In Latin America, only 33% of study participants had alcohol-related cirrhosis in contrast to 67% of those in North America.

However, “comorbidities across the world were similar, and MELD scores were also similar,” Dr. Jalan said.
 

Death or Delisting

Between listing and transplantation, 28% of patients in group 1 either died or were delisted, compared with 16% of those in group 2. In group 3, 85% of patients who were not listed for transplantation in the first place died.

Similar to what has been seen in other studies, nearly 50% of patients with ACLF 3 but a MELD score < 25 on the wait list died or were delisted, Dr. Jalan pointed out, suggesting that these patients are disadvantaged under the current system of waiting list priority.

Geographically, deaths on the wait list were significantly higher in Latin America at 40% than in North America, Europe, and Asia at 20%, 18%, and 13%, respectively.

“This is likely due to low donation rates in Latin America,” Dr. Jalan said.

Turning to 3-month post-transplantation mortality, the rates in groups 1 and 2 were 9% and 7%, respectively.

“This demonstrates very nicely the clear benefit of transplant,” Dr. Jalan said. “The risk of death post transplant, even with ACLF 2 or 3, is not significantly different to those patients with decompensated cirrhosis.”

There was a slightly higher risk for death in patients with ACLF 3 than in those with ACLF 2 at 14% vs 7%, but “the risk of death in these patients if they don’t have transportation is 70%-80%,” he said.

Looking at 3-month post-transplantation mortality by continent, Dr. Jalan highlighted that Latin America showed 16% risk, compared with Asia, Europe, and North America that showed 12%, 7%, and 3% risk, respectively.

“This is probably multifactorial and likely to be influenced by time on the waiting list, quality of organs available, and patient demographics, among other factors,” Dr. Jalan said. When very sick people undergo transplantation, “there is a higher risk of death.”

The patients in this study have waited a long time, “which worsens their situation,” said Dr. Jalan, reinforcing his argument for changing the international organ allocation system to allow earlier access for these patients.
 

‘The Landscape of Organ Allocation Is Extremely Complex’

Comoderator Ana Lleo, MD, PhD, full professor of internal medicine and hepatology, Humanitas University, Milan, Italy, commented that “the number of patients included in this international study is significant,” and that the issue of mortality on the wait list is of great clinical interest.

“The landscape of organ allocation is extremely complex,” she added.

The system for liver transplantation considers a large number of clinical conditions with very diverse benefit profiles, she explained.

“While we would like to offer liver transplantation for all patients with any range of benefit, the current donations are not sufficient to cover the request,” Dr. Lleo said. “Therefore, prioritization remains key.”

The findings do illustrate the inadequacy of current transplantation allocation criteria for patients with ACLF 2 and 3, said Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College Hospital, London, England, who is also serving as vice-secretary of the EASL Governing Board.

However, “this must be balanced by the recognition that the global donor pool of organs available is a finite resource,” she said, echoing Dr. Lleo’s comments.

This calls for wider ethical discussions to avoid disadvantaging more stable, often younger patients with cirrhosis who are listed for transplantation, she added.

Dr. Jalan declared he is the inventor of Ornithine Phenylacetate, licensed by UCL to Mallinckrodt Pharma; a speaker and grant reviewer for Grifols Research Collaboration: Yaqrit; and the founder of Yaqrit, Hepyx, CyberLiver, and Gigabiome. Dr. Lleo declared that she does not have any conflicts relevant to this work but received lecture fees from Gilead, Advanz Pharma, Alfasigma, GSK, Incyte, Gore, AstraZeneca, and Ipsen and consulted for Advanz Pharma, AstraZeneca, Ipsen, GSK, and Dr Falk. Dr. Shawcross declared advisory board/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.

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

MILAN — Survodutide, an investigational dual glucagon-like peptide 1 (GLP-1) and glucagon receptor agonist, led to “exceptional improvement in disease activity and fibrosis” in patients with metabolic dysfunction–associated steatohepatitis (MASH), according to phase 2 results presented here at the European Association for the Study of the Liver (EASL) Congress 2024.

The data were simultaneously published in The New England Journal of Medicine .

The primary endpoint data, reported earlier this year in a press release, showed that up to 83% of participants on survodutide showed a statistically significant improvement in MASH compared with those on placebo (18.2%) based on paired biopsy results.

In addition, 75% of patients treated with survodutide experienced resolution of MASH with no worsening of fibrosis compared with 15% of patients on placebo, and in patients with F2/F3 fibrosis, 64.5% achieved improvement in fibrosis without worsening of MASH, reported Arun J. Sanyal, MD, principal study investigator and director of the Virginia Commonwealth University (VCU) Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, Virginia.

American Association for the Study of Liver Diseases

What’s so amazing is that this “exceptional improvement” is after 48 weeks of therapy with a class of molecule that is already known to also have cardiometabolic benefits, Dr. Sanyal said in an interview.

“At the highest dose of survodutide [6.0 mg], two thirds of patients in whom we have biopsy data, at both the beginning and the end, actually showed fibrosis regression within 48 weeks,” he said. “This is pretty dramatic.”
 

Efficacy and Safety of Survodutide

A total of 293 participants with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned (1:1:1:1) to receive once-weekly subcutaneous injections of survodutide 2.4 mg (n = 73), 4.8 mg (n = 72), or 6.0 mg (n = 74) or placebo (n = 74).

Around half of study participants were women, with mean age around 50 years and a body mass index around 35 kg/m². Overall, 26%-30% had type 2 diabetes, 24%-36% had F2 fibrosis, and 23%-30% had F3 fibrosis. The total Nonalcoholic Fatty Liver Disease Activity Score was 5.2.

After completing a 24-week rapid-dose-escalation phase, participants followed a 24-week maintenance phase. Histologic improvement (reduction) in MASH without worsening of fibrosis after 48 weeks of treatment comprised the primary endpoint, whereas a reduction in liver fat content by at least 30% and biopsy-assessed reduction in fibrosis by at least one stage were among the secondary endpoints.

The main analyses of the trial were based on two treatment sets: Actual treatment (the actual dose received at the start of the maintenance phase; per protocol) and planned treatment (the maintenance dose assigned to participants at randomization). Dr. Sanyal mainly reported results based on actual treatment, which were used for the primary analysis.

The overall primary endpoint data, including nonresponders, showed a 47% improvement in MASH in the 2.4-mg treatment group, 62% in the 4.8 mg group, and 43% in the 6.0-mg group compared with 13.5% in the placebo group (P < .001).

In addition, 50% of patients on 2.4- and 6-mg doses experienced a statistically significant improvement in fibrosis (F1-F3) without worsening of MASH. In patients with F2/F3 fibrosis, 64.5% of participants in the 6-mg survodutide group showed improvement vs 25.9% in the placebo group.

Reduction in liver fat by at least 30% was achieved by up to 87% in the 6-mg group according to MRI-estimated proton density fat fraction; when nonresponders were included, the percentage was 76.9% of the 6-mg group. Other outcomes included weight loss and reductions in A1c.

The results did not differ markedly between doses, which “is really exciting news,” Dr. Sanyal said.

Patients who are intolerant of the highest dose can switch to a lower dose without a big loss of efficacy, he said, adding that even the low dose was sufficient to get near maximal glucagon effect.

Adverse events were similar between survodutide and placebo, except for gastrointestinal events, including nausea, diarrhea, and vomiting. The occurrence of serious adverse events also was similar between survodutide and placebo.

Discontinuation due to adverse events was 20% across all the survodutide groups (with 16% due to gastrointestinal events) vs 3% in the placebo group.
 

Dual Agonist vs Monoagonist Therapy

The dual agonist approach may confer clinical advantages over GLP-1 receptor monoagonist pharmacotherapies for MASH.

“GLP has no receptors in the liver, so all its effects are mediated outside the liver, particularly for weight loss and improvement in metabolic status, increase in insulin secretion and sensitivity, and overall systemic glycemia,” Dr. Sanyal explained.

“People with established fibrosis take longer to respond in terms of downstream liver scarring with extrahepatic changes alone,” he added.

With “glucagon directly targeting the liver, we believe this reduces oxidative stress and possibly stimulates FGF-21 secretion [liver-derived factor that regulates lipid and glucose metabolism] in the liver, so there are likely multiple mechanisms driving the antifibrogenic benefits,” Dr. Sanyal said.

In comparison, the study authors highlighted that data on the GLP-1 receptor monoagonist semaglutide suggest a significantly higher proportion of patients on semaglutide achieve MASH resolution than those on placebo but that it does not result in “a significantly higher percentage of patients with improvement in fibrosis stage.

“It might be that it takes longer to get an effect in the liver with semaglutide,” Dr. Sanyal said.

By year-end, we’ll know how the GLP-1 alone approach (eg, semaglutide) and the dual agonist approach work, and we’ll eventually have data on triple agonists, Dr. Sanyal added.
 

The Burden of Liver Disease

Comoderator Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College, London, England, remarked on the importance of new drugs, including survodutide, in reducing the burden of steatotic liver disease.

Approximately one third of the world’s population and between 7% and 9% of children have steatotic liver disease, she noted. The buildup of fat causes inflammation and scarring of the liver, which may then progress to liver cirrhosis and primary liver cancers.

Survodutide offers much hope “as a drug that will reduce both liver inflammation and scarring, while also providing the benefit of improved diabetic control,” Dr. Shawcross said.

Reflecting on the dual agonism, she said that both the glucagon and GLP-1 receptors are critical to controlling metabolic functions.

Survodutide is currently being investigated in five phase 3 studies for people living with overweight and obesity, both of which are associated with MASH. There is also a trial looking at people with overweight/obesity with confirmed or presumed diagnosis of MASH, according to a company press release.

Dr. Sanyal reported grants, consultancy fees, and speaker fees from a wide range of companies working in the field of liver medicine. Dr. Shawcross reported no conflicts in relation to this drug and advisory board membership/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.
 

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

MILAN — Survodutide, an investigational dual glucagon-like peptide 1 (GLP-1) and glucagon receptor agonist, led to “exceptional improvement in disease activity and fibrosis” in patients with metabolic dysfunction–associated steatohepatitis (MASH), according to phase 2 results presented here at the European Association for the Study of the Liver (EASL) Congress 2024.

The data were simultaneously published in The New England Journal of Medicine .

The primary endpoint data, reported earlier this year in a press release, showed that up to 83% of participants on survodutide showed a statistically significant improvement in MASH compared with those on placebo (18.2%) based on paired biopsy results.

In addition, 75% of patients treated with survodutide experienced resolution of MASH with no worsening of fibrosis compared with 15% of patients on placebo, and in patients with F2/F3 fibrosis, 64.5% achieved improvement in fibrosis without worsening of MASH, reported Arun J. Sanyal, MD, principal study investigator and director of the Virginia Commonwealth University (VCU) Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, Virginia.

American Association for the Study of Liver Diseases

What’s so amazing is that this “exceptional improvement” is after 48 weeks of therapy with a class of molecule that is already known to also have cardiometabolic benefits, Dr. Sanyal said in an interview.

“At the highest dose of survodutide [6.0 mg], two thirds of patients in whom we have biopsy data, at both the beginning and the end, actually showed fibrosis regression within 48 weeks,” he said. “This is pretty dramatic.”
 

Efficacy and Safety of Survodutide

A total of 293 participants with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned (1:1:1:1) to receive once-weekly subcutaneous injections of survodutide 2.4 mg (n = 73), 4.8 mg (n = 72), or 6.0 mg (n = 74) or placebo (n = 74).

Around half of study participants were women, with mean age around 50 years and a body mass index around 35 kg/m². Overall, 26%-30% had type 2 diabetes, 24%-36% had F2 fibrosis, and 23%-30% had F3 fibrosis. The total Nonalcoholic Fatty Liver Disease Activity Score was 5.2.

After completing a 24-week rapid-dose-escalation phase, participants followed a 24-week maintenance phase. Histologic improvement (reduction) in MASH without worsening of fibrosis after 48 weeks of treatment comprised the primary endpoint, whereas a reduction in liver fat content by at least 30% and biopsy-assessed reduction in fibrosis by at least one stage were among the secondary endpoints.

The main analyses of the trial were based on two treatment sets: Actual treatment (the actual dose received at the start of the maintenance phase; per protocol) and planned treatment (the maintenance dose assigned to participants at randomization). Dr. Sanyal mainly reported results based on actual treatment, which were used for the primary analysis.

The overall primary endpoint data, including nonresponders, showed a 47% improvement in MASH in the 2.4-mg treatment group, 62% in the 4.8 mg group, and 43% in the 6.0-mg group compared with 13.5% in the placebo group (P < .001).

In addition, 50% of patients on 2.4- and 6-mg doses experienced a statistically significant improvement in fibrosis (F1-F3) without worsening of MASH. In patients with F2/F3 fibrosis, 64.5% of participants in the 6-mg survodutide group showed improvement vs 25.9% in the placebo group.

Reduction in liver fat by at least 30% was achieved by up to 87% in the 6-mg group according to MRI-estimated proton density fat fraction; when nonresponders were included, the percentage was 76.9% of the 6-mg group. Other outcomes included weight loss and reductions in A1c.

The results did not differ markedly between doses, which “is really exciting news,” Dr. Sanyal said.

Patients who are intolerant of the highest dose can switch to a lower dose without a big loss of efficacy, he said, adding that even the low dose was sufficient to get near maximal glucagon effect.

Adverse events were similar between survodutide and placebo, except for gastrointestinal events, including nausea, diarrhea, and vomiting. The occurrence of serious adverse events also was similar between survodutide and placebo.

Discontinuation due to adverse events was 20% across all the survodutide groups (with 16% due to gastrointestinal events) vs 3% in the placebo group.
 

Dual Agonist vs Monoagonist Therapy

The dual agonist approach may confer clinical advantages over GLP-1 receptor monoagonist pharmacotherapies for MASH.

“GLP has no receptors in the liver, so all its effects are mediated outside the liver, particularly for weight loss and improvement in metabolic status, increase in insulin secretion and sensitivity, and overall systemic glycemia,” Dr. Sanyal explained.

“People with established fibrosis take longer to respond in terms of downstream liver scarring with extrahepatic changes alone,” he added.

With “glucagon directly targeting the liver, we believe this reduces oxidative stress and possibly stimulates FGF-21 secretion [liver-derived factor that regulates lipid and glucose metabolism] in the liver, so there are likely multiple mechanisms driving the antifibrogenic benefits,” Dr. Sanyal said.

In comparison, the study authors highlighted that data on the GLP-1 receptor monoagonist semaglutide suggest a significantly higher proportion of patients on semaglutide achieve MASH resolution than those on placebo but that it does not result in “a significantly higher percentage of patients with improvement in fibrosis stage.

“It might be that it takes longer to get an effect in the liver with semaglutide,” Dr. Sanyal said.

By year-end, we’ll know how the GLP-1 alone approach (eg, semaglutide) and the dual agonist approach work, and we’ll eventually have data on triple agonists, Dr. Sanyal added.
 

The Burden of Liver Disease

Comoderator Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College, London, England, remarked on the importance of new drugs, including survodutide, in reducing the burden of steatotic liver disease.

Approximately one third of the world’s population and between 7% and 9% of children have steatotic liver disease, she noted. The buildup of fat causes inflammation and scarring of the liver, which may then progress to liver cirrhosis and primary liver cancers.

Survodutide offers much hope “as a drug that will reduce both liver inflammation and scarring, while also providing the benefit of improved diabetic control,” Dr. Shawcross said.

Reflecting on the dual agonism, she said that both the glucagon and GLP-1 receptors are critical to controlling metabolic functions.

Survodutide is currently being investigated in five phase 3 studies for people living with overweight and obesity, both of which are associated with MASH. There is also a trial looking at people with overweight/obesity with confirmed or presumed diagnosis of MASH, according to a company press release.

Dr. Sanyal reported grants, consultancy fees, and speaker fees from a wide range of companies working in the field of liver medicine. Dr. Shawcross reported no conflicts in relation to this drug and advisory board membership/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.
 

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

MILAN — Survodutide, an investigational dual glucagon-like peptide 1 (GLP-1) and glucagon receptor agonist, led to “exceptional improvement in disease activity and fibrosis” in patients with metabolic dysfunction–associated steatohepatitis (MASH), according to phase 2 results presented here at the European Association for the Study of the Liver (EASL) Congress 2024.

The data were simultaneously published in The New England Journal of Medicine .

The primary endpoint data, reported earlier this year in a press release, showed that up to 83% of participants on survodutide showed a statistically significant improvement in MASH compared with those on placebo (18.2%) based on paired biopsy results.

In addition, 75% of patients treated with survodutide experienced resolution of MASH with no worsening of fibrosis compared with 15% of patients on placebo, and in patients with F2/F3 fibrosis, 64.5% achieved improvement in fibrosis without worsening of MASH, reported Arun J. Sanyal, MD, principal study investigator and director of the Virginia Commonwealth University (VCU) Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, VCU School of Medicine, Richmond, Virginia.

American Association for the Study of Liver Diseases

What’s so amazing is that this “exceptional improvement” is after 48 weeks of therapy with a class of molecule that is already known to also have cardiometabolic benefits, Dr. Sanyal said in an interview.

“At the highest dose of survodutide [6.0 mg], two thirds of patients in whom we have biopsy data, at both the beginning and the end, actually showed fibrosis regression within 48 weeks,” he said. “This is pretty dramatic.”
 

Efficacy and Safety of Survodutide

A total of 293 participants with biopsy-confirmed MASH and fibrosis stages F1-F3 were randomly assigned (1:1:1:1) to receive once-weekly subcutaneous injections of survodutide 2.4 mg (n = 73), 4.8 mg (n = 72), or 6.0 mg (n = 74) or placebo (n = 74).

Around half of study participants were women, with mean age around 50 years and a body mass index around 35 kg/m². Overall, 26%-30% had type 2 diabetes, 24%-36% had F2 fibrosis, and 23%-30% had F3 fibrosis. The total Nonalcoholic Fatty Liver Disease Activity Score was 5.2.

After completing a 24-week rapid-dose-escalation phase, participants followed a 24-week maintenance phase. Histologic improvement (reduction) in MASH without worsening of fibrosis after 48 weeks of treatment comprised the primary endpoint, whereas a reduction in liver fat content by at least 30% and biopsy-assessed reduction in fibrosis by at least one stage were among the secondary endpoints.

The main analyses of the trial were based on two treatment sets: Actual treatment (the actual dose received at the start of the maintenance phase; per protocol) and planned treatment (the maintenance dose assigned to participants at randomization). Dr. Sanyal mainly reported results based on actual treatment, which were used for the primary analysis.

The overall primary endpoint data, including nonresponders, showed a 47% improvement in MASH in the 2.4-mg treatment group, 62% in the 4.8 mg group, and 43% in the 6.0-mg group compared with 13.5% in the placebo group (P < .001).

In addition, 50% of patients on 2.4- and 6-mg doses experienced a statistically significant improvement in fibrosis (F1-F3) without worsening of MASH. In patients with F2/F3 fibrosis, 64.5% of participants in the 6-mg survodutide group showed improvement vs 25.9% in the placebo group.

Reduction in liver fat by at least 30% was achieved by up to 87% in the 6-mg group according to MRI-estimated proton density fat fraction; when nonresponders were included, the percentage was 76.9% of the 6-mg group. Other outcomes included weight loss and reductions in A1c.

The results did not differ markedly between doses, which “is really exciting news,” Dr. Sanyal said.

Patients who are intolerant of the highest dose can switch to a lower dose without a big loss of efficacy, he said, adding that even the low dose was sufficient to get near maximal glucagon effect.

Adverse events were similar between survodutide and placebo, except for gastrointestinal events, including nausea, diarrhea, and vomiting. The occurrence of serious adverse events also was similar between survodutide and placebo.

Discontinuation due to adverse events was 20% across all the survodutide groups (with 16% due to gastrointestinal events) vs 3% in the placebo group.
 

Dual Agonist vs Monoagonist Therapy

The dual agonist approach may confer clinical advantages over GLP-1 receptor monoagonist pharmacotherapies for MASH.

“GLP has no receptors in the liver, so all its effects are mediated outside the liver, particularly for weight loss and improvement in metabolic status, increase in insulin secretion and sensitivity, and overall systemic glycemia,” Dr. Sanyal explained.

“People with established fibrosis take longer to respond in terms of downstream liver scarring with extrahepatic changes alone,” he added.

With “glucagon directly targeting the liver, we believe this reduces oxidative stress and possibly stimulates FGF-21 secretion [liver-derived factor that regulates lipid and glucose metabolism] in the liver, so there are likely multiple mechanisms driving the antifibrogenic benefits,” Dr. Sanyal said.

In comparison, the study authors highlighted that data on the GLP-1 receptor monoagonist semaglutide suggest a significantly higher proportion of patients on semaglutide achieve MASH resolution than those on placebo but that it does not result in “a significantly higher percentage of patients with improvement in fibrosis stage.

“It might be that it takes longer to get an effect in the liver with semaglutide,” Dr. Sanyal said.

By year-end, we’ll know how the GLP-1 alone approach (eg, semaglutide) and the dual agonist approach work, and we’ll eventually have data on triple agonists, Dr. Sanyal added.
 

The Burden of Liver Disease

Comoderator Debbie Shawcross, MBBS, PhD, professor of hepatology and chronic liver failure, King’s College, London, England, remarked on the importance of new drugs, including survodutide, in reducing the burden of steatotic liver disease.

Approximately one third of the world’s population and between 7% and 9% of children have steatotic liver disease, she noted. The buildup of fat causes inflammation and scarring of the liver, which may then progress to liver cirrhosis and primary liver cancers.

Survodutide offers much hope “as a drug that will reduce both liver inflammation and scarring, while also providing the benefit of improved diabetic control,” Dr. Shawcross said.

Reflecting on the dual agonism, she said that both the glucagon and GLP-1 receptors are critical to controlling metabolic functions.

Survodutide is currently being investigated in five phase 3 studies for people living with overweight and obesity, both of which are associated with MASH. There is also a trial looking at people with overweight/obesity with confirmed or presumed diagnosis of MASH, according to a company press release.

Dr. Sanyal reported grants, consultancy fees, and speaker fees from a wide range of companies working in the field of liver medicine. Dr. Shawcross reported no conflicts in relation to this drug and advisory board membership/consultancy for EnteroBiotix, Norgine, Satellite Bio, and MRN Health.
 

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

FHM is a rare phenotype of migraine with aura with a characteristic presentation of motor aura. Motor aura presents as unilateral muscle weakness that tends to be felt first in the hands or arm and may spread to the face. To date, three distinct types have been identified by mutations in one of three genes. Type 1 is the most common and is associated with mutations in the gene CACNA1A. Mutations in ATP1A2 underlie type 2 FHM, and mutations in SCN1A underlie type 3 FHM.

FHM is distinguished from other hemiplegic migraine by family history of one or more affected first- or second-degree relatives. Genetic studies have shown FHM to have autosomal dominant inheritance. From half to three quarters of patients with FHM will have one of the more than 30 identified mutations on CACNA1A that diagnose type 1 FHM. These mutations affect transmission of glutamate in the neurons and neuronal reactions, increasing the susceptibility to cortical spreading depression associated with migraine. Mutations in ATP1A2 are found in about 20% of patients with FHM (type 2). More than 80 individual mutations have been identified, which alter sodium-potassium metabolism in neurons. About 5% of patients have type 3 FHM, associated with mutations in SCN1A that create gain of function or loss of function in neuronal voltage-gated sodium channels. Studies of other possible genes and mutations in relation to FHM, including PRRT2, are ongoing, but to date the associations are not clearly established. 

Patients with FHM may also report sensory symptoms, visual disturbances, or aphasia. FHM generally affects people in their teens and twenties (women more than men) and has an estimated prevalence of 0.003% of the population. On average, patients report having two to three attacks per year, and some patients go for extended periods without a recurrent attack. Motor aura may occur on the same or opposite side of the body as headache and may alternate affected sides with each attack. Differential diagnoses that should be ruled out include transient ischemic attacks, infections (eg, meningitis, encephalitis), tumors, seizures, other inherited disorders, and metabolic issues.

Like other forms of migraine with aura, FHM is treated with abortive and/or preventive medications. Given the rarity of FHM, there are few studies specifically in families with this phenotype. Patients should be counseled on trigger avoidance to limit exposure. Acute treatment includes nonsteroidal anti-inflammatory drugs, acetaminophen, and other nonopioid pain relievers. The class of calcitonin gene-related peptide (CGRP) antagonists (rimegepant, ubrogepant, zavegepant) may be considered. However, with FHM, medications associated with ischemia must be avoided. As such, triptans and ergotamines are generally contraindicated, as are beta-blockers. Patients with FHM and more frequent or severe attacks may be considered for preventive treatment to improve function and quality of life and avoid reliance on acute therapies. Options include CGRP monoclonal antibodies (mAbs), administered subcutaneously or by intravenous infusion, and onabotulinumtoxinA injection. Current CGRP mAbs include eptinezumab, erenumab, fremanezumab, and galcanezumab. Combined CGRP mAb therapy with onabotulinumtoxinA may be an effective alternative for patients with resistant FHM. 

Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Heidi Moawad, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

FHM is a rare phenotype of migraine with aura with a characteristic presentation of motor aura. Motor aura presents as unilateral muscle weakness that tends to be felt first in the hands or arm and may spread to the face. To date, three distinct types have been identified by mutations in one of three genes. Type 1 is the most common and is associated with mutations in the gene CACNA1A. Mutations in ATP1A2 underlie type 2 FHM, and mutations in SCN1A underlie type 3 FHM.

FHM is distinguished from other hemiplegic migraine by family history of one or more affected first- or second-degree relatives. Genetic studies have shown FHM to have autosomal dominant inheritance. From half to three quarters of patients with FHM will have one of the more than 30 identified mutations on CACNA1A that diagnose type 1 FHM. These mutations affect transmission of glutamate in the neurons and neuronal reactions, increasing the susceptibility to cortical spreading depression associated with migraine. Mutations in ATP1A2 are found in about 20% of patients with FHM (type 2). More than 80 individual mutations have been identified, which alter sodium-potassium metabolism in neurons. About 5% of patients have type 3 FHM, associated with mutations in SCN1A that create gain of function or loss of function in neuronal voltage-gated sodium channels. Studies of other possible genes and mutations in relation to FHM, including PRRT2, are ongoing, but to date the associations are not clearly established. 

Patients with FHM may also report sensory symptoms, visual disturbances, or aphasia. FHM generally affects people in their teens and twenties (women more than men) and has an estimated prevalence of 0.003% of the population. On average, patients report having two to three attacks per year, and some patients go for extended periods without a recurrent attack. Motor aura may occur on the same or opposite side of the body as headache and may alternate affected sides with each attack. Differential diagnoses that should be ruled out include transient ischemic attacks, infections (eg, meningitis, encephalitis), tumors, seizures, other inherited disorders, and metabolic issues.

Like other forms of migraine with aura, FHM is treated with abortive and/or preventive medications. Given the rarity of FHM, there are few studies specifically in families with this phenotype. Patients should be counseled on trigger avoidance to limit exposure. Acute treatment includes nonsteroidal anti-inflammatory drugs, acetaminophen, and other nonopioid pain relievers. The class of calcitonin gene-related peptide (CGRP) antagonists (rimegepant, ubrogepant, zavegepant) may be considered. However, with FHM, medications associated with ischemia must be avoided. As such, triptans and ergotamines are generally contraindicated, as are beta-blockers. Patients with FHM and more frequent or severe attacks may be considered for preventive treatment to improve function and quality of life and avoid reliance on acute therapies. Options include CGRP monoclonal antibodies (mAbs), administered subcutaneously or by intravenous infusion, and onabotulinumtoxinA injection. Current CGRP mAbs include eptinezumab, erenumab, fremanezumab, and galcanezumab. Combined CGRP mAb therapy with onabotulinumtoxinA may be an effective alternative for patients with resistant FHM. 

Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Heidi Moawad, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

FHM is a rare phenotype of migraine with aura with a characteristic presentation of motor aura. Motor aura presents as unilateral muscle weakness that tends to be felt first in the hands or arm and may spread to the face. To date, three distinct types have been identified by mutations in one of three genes. Type 1 is the most common and is associated with mutations in the gene CACNA1A. Mutations in ATP1A2 underlie type 2 FHM, and mutations in SCN1A underlie type 3 FHM.

FHM is distinguished from other hemiplegic migraine by family history of one or more affected first- or second-degree relatives. Genetic studies have shown FHM to have autosomal dominant inheritance. From half to three quarters of patients with FHM will have one of the more than 30 identified mutations on CACNA1A that diagnose type 1 FHM. These mutations affect transmission of glutamate in the neurons and neuronal reactions, increasing the susceptibility to cortical spreading depression associated with migraine. Mutations in ATP1A2 are found in about 20% of patients with FHM (type 2). More than 80 individual mutations have been identified, which alter sodium-potassium metabolism in neurons. About 5% of patients have type 3 FHM, associated with mutations in SCN1A that create gain of function or loss of function in neuronal voltage-gated sodium channels. Studies of other possible genes and mutations in relation to FHM, including PRRT2, are ongoing, but to date the associations are not clearly established. 

Patients with FHM may also report sensory symptoms, visual disturbances, or aphasia. FHM generally affects people in their teens and twenties (women more than men) and has an estimated prevalence of 0.003% of the population. On average, patients report having two to three attacks per year, and some patients go for extended periods without a recurrent attack. Motor aura may occur on the same or opposite side of the body as headache and may alternate affected sides with each attack. Differential diagnoses that should be ruled out include transient ischemic attacks, infections (eg, meningitis, encephalitis), tumors, seizures, other inherited disorders, and metabolic issues.

Like other forms of migraine with aura, FHM is treated with abortive and/or preventive medications. Given the rarity of FHM, there are few studies specifically in families with this phenotype. Patients should be counseled on trigger avoidance to limit exposure. Acute treatment includes nonsteroidal anti-inflammatory drugs, acetaminophen, and other nonopioid pain relievers. The class of calcitonin gene-related peptide (CGRP) antagonists (rimegepant, ubrogepant, zavegepant) may be considered. However, with FHM, medications associated with ischemia must be avoided. As such, triptans and ergotamines are generally contraindicated, as are beta-blockers. Patients with FHM and more frequent or severe attacks may be considered for preventive treatment to improve function and quality of life and avoid reliance on acute therapies. Options include CGRP monoclonal antibodies (mAbs), administered subcutaneously or by intravenous infusion, and onabotulinumtoxinA injection. Current CGRP mAbs include eptinezumab, erenumab, fremanezumab, and galcanezumab. Combined CGRP mAb therapy with onabotulinumtoxinA may be an effective alternative for patients with resistant FHM. 

Heidi Moawad, MD, Clinical Assistant Professor, Department of Medical Education, Case Western Reserve University School of Medicine, Cleveland, Ohio.

Heidi Moawad, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Meet Our New Chair

Douglas J. Robertson, MD, MPH, AGAFAGA Institute Council Chair

VA Medical Center, White River Junction, Vermont

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire

Dr. Robertson will serve as council chair for 3 years (May 2024-May 2027; DDW 2025, 2026 and 2027).

Geisel School of Medicine

Section Leadership

We are pleased to announce the results of the elections held recently by the AGA Institute Council, the driving force behind AGA’s programming at Digestive Disease Week (DDW). We welcome 8 members into their new roles as section vice chairs, joining the existing 17 Council members. Each new vice chair will serve a 2-year term that began immediately following this year’s DDW meeting and extends through DDW 2026. Following their term as vice chair, they will move into the role of section chair for an additional 2 years through DDW 2028.

AGA

We are also pleased to announce the members joining nominating committees during the 2026 nomination/election cycle. The chairs of the nominating committee will be the immediate past section chairs, whom we also recognize and thank for their service and dedication to the section and the council.
 

Basic & Clinical Intestinal Disorders (BCID)

Uma Sundaram, MDVice chair

Marshall University School of Medicine, Huntington, West Virginia

Nominating committee members

• Colleen Renee Kelly, MD, AGAF, Chair
• Amy C. Engevik, PhD, Medical University of South Carolina
• Ravinder Gill, PhD, University of Illinois at Chicago
• Madhusudan Grover, MD, Mayo Clinic, Rochester, Minnesota
• Lisa L. Strate, MD, Harborview Medical Center, Seattle

Clinical Practice (CP)

Linda Anh Nguyen, MDVice Chair

Stanford (Calif.) University School of Medicine

Nominating committee members

• Gary W. Falk, MD, MS, AGAF, Chair
• Megan Adams, MD, JD, MSc, VA Ann Arbor Healthcare System Endoscopy Unit
• Mohammad Bilal, MD, Minneapolis VA Health Care System
• Carolyn Newberry, MD, Weill Cornell Medical Center, New York
• Adam Weizman, MD, MSc, Mount Sinai Hospital, Toronto

Endoscopy, Technology & Imaging (ETI)

Vivek Kaul, MD, AGAFVice Chair

University of Rochester (N.Y.) Medical Center

Nominating committee members

• Irving Waxman, MD, Chair
• Sushovan Guha, MD, PhD, University of Texas at Houston
• Pichamol Jirapinyo, MD, MPH, Brigham and Women’s Hospital, Boston
• Vladimir Kushnir, MD, Washington University St. Louis Barnes–Jewish West County Hospital
• Andrew C. Storm, MD, Mayo Clinic, Rochester, Minnesota

Immunology, Microbiology & Inflammatory Bowel Diseases (IMIBD)

Florian Rieder, MDVice Chair

Cleveland Clinic Foundation

Nominating committee members

• Fernando S. Velayos, MD, AGAF, Chair
• Brigid S. Boland, MD, University of California, San Diego
• Karen L. Edelblum, PhD, Icahn School of Medicine at Mount Sinai, New York
• Michael Kattah, MD, PhD, UCSF Gastroenterology
• Andres J. Yarur, MD, Cedars Sinai Medical Center. Los Angeles

Liver & Biliary (LB)

Don Rockey, MDVice Chair

Medical University of South Carolina, Charleston

Nominating committee members

• Gyongyi Szabo, MD, PhD, AGAF, Chair
• Brett Fortune, MD, MSc, Montefiore Medical Center
• Ruben Hernaez, MD, MPH, PhD, Baylor College of Medicine, Houston
• Cynthia Ann Moylan, MD, MHS, MS, Duke University, Durham, North Carolina
• Douglas A. Simonetto, MD, Mayo Clinic, Rochester, Minnesota

Microbiome & Microbial Therapy (MMT)

Jessica Allegretti, MD, MPHVice Chair

Brigham and Women’s Hospital, Boston

Nominating committee members

• Purna C. Kashyap, MBBS, AGAF, Chair
• Melinda Engevik, PhD, Medical University of South Carolina
• Christian Jobin, PhD, University of Florida
• Vanessa Leone, PhD, The University of Wisconsin–Madison
• Jun Yu, MD, PhD, The Chinese University of Hong Kong

Obesity, Metabolism & Nutrition (OMN)

Berkeley M. Limketkai, MD, PhDVice Chair

University of California Los Angeles

Nominating committee members

• Andres Jose Acosta, MD, PhD, Chair
• Barham K. Abu Dayyeh, MD, MPH, Mayo Clinic, Rochester, Minnesota
• Alan L. Buchman, MD, MSPH, University of Illinois at Chicago
• Octavia Pickett-Blakely, MD, MHS, Hospital of the University of Pennsylvania
• Robert Shulman, MD, Texas Children’s Hospital, Baylor College of Medicine

Pediatric Gastroenterology & Developmental Biology (PGDB)

Kelli L. VanDussen, PhDVice Chair

Cincinnati Children’s Hospital Medical Center 

Meet Our New Chair

Douglas J. Robertson, MD, MPH, AGAFAGA Institute Council Chair

VA Medical Center, White River Junction, Vermont

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire

Dr. Robertson will serve as council chair for 3 years (May 2024-May 2027; DDW 2025, 2026 and 2027).

Geisel School of Medicine

Section Leadership

We are pleased to announce the results of the elections held recently by the AGA Institute Council, the driving force behind AGA’s programming at Digestive Disease Week (DDW). We welcome 8 members into their new roles as section vice chairs, joining the existing 17 Council members. Each new vice chair will serve a 2-year term that began immediately following this year’s DDW meeting and extends through DDW 2026. Following their term as vice chair, they will move into the role of section chair for an additional 2 years through DDW 2028.

AGA

We are also pleased to announce the members joining nominating committees during the 2026 nomination/election cycle. The chairs of the nominating committee will be the immediate past section chairs, whom we also recognize and thank for their service and dedication to the section and the council.
 

Basic & Clinical Intestinal Disorders (BCID)

Uma Sundaram, MDVice chair

Marshall University School of Medicine, Huntington, West Virginia

Nominating committee members

• Colleen Renee Kelly, MD, AGAF, Chair
• Amy C. Engevik, PhD, Medical University of South Carolina
• Ravinder Gill, PhD, University of Illinois at Chicago
• Madhusudan Grover, MD, Mayo Clinic, Rochester, Minnesota
• Lisa L. Strate, MD, Harborview Medical Center, Seattle

Clinical Practice (CP)

Linda Anh Nguyen, MDVice Chair

Stanford (Calif.) University School of Medicine

Nominating committee members

• Gary W. Falk, MD, MS, AGAF, Chair
• Megan Adams, MD, JD, MSc, VA Ann Arbor Healthcare System Endoscopy Unit
• Mohammad Bilal, MD, Minneapolis VA Health Care System
• Carolyn Newberry, MD, Weill Cornell Medical Center, New York
• Adam Weizman, MD, MSc, Mount Sinai Hospital, Toronto

Endoscopy, Technology & Imaging (ETI)

Vivek Kaul, MD, AGAFVice Chair

University of Rochester (N.Y.) Medical Center

Nominating committee members

• Irving Waxman, MD, Chair
• Sushovan Guha, MD, PhD, University of Texas at Houston
• Pichamol Jirapinyo, MD, MPH, Brigham and Women’s Hospital, Boston
• Vladimir Kushnir, MD, Washington University St. Louis Barnes–Jewish West County Hospital
• Andrew C. Storm, MD, Mayo Clinic, Rochester, Minnesota

Immunology, Microbiology & Inflammatory Bowel Diseases (IMIBD)

Florian Rieder, MDVice Chair

Cleveland Clinic Foundation

Nominating committee members

• Fernando S. Velayos, MD, AGAF, Chair
• Brigid S. Boland, MD, University of California, San Diego
• Karen L. Edelblum, PhD, Icahn School of Medicine at Mount Sinai, New York
• Michael Kattah, MD, PhD, UCSF Gastroenterology
• Andres J. Yarur, MD, Cedars Sinai Medical Center. Los Angeles

Liver & Biliary (LB)

Don Rockey, MDVice Chair

Medical University of South Carolina, Charleston

Nominating committee members

• Gyongyi Szabo, MD, PhD, AGAF, Chair
• Brett Fortune, MD, MSc, Montefiore Medical Center
• Ruben Hernaez, MD, MPH, PhD, Baylor College of Medicine, Houston
• Cynthia Ann Moylan, MD, MHS, MS, Duke University, Durham, North Carolina
• Douglas A. Simonetto, MD, Mayo Clinic, Rochester, Minnesota

Microbiome & Microbial Therapy (MMT)

Jessica Allegretti, MD, MPHVice Chair

Brigham and Women’s Hospital, Boston

Nominating committee members

• Purna C. Kashyap, MBBS, AGAF, Chair
• Melinda Engevik, PhD, Medical University of South Carolina
• Christian Jobin, PhD, University of Florida
• Vanessa Leone, PhD, The University of Wisconsin–Madison
• Jun Yu, MD, PhD, The Chinese University of Hong Kong

Obesity, Metabolism & Nutrition (OMN)

Berkeley M. Limketkai, MD, PhDVice Chair

University of California Los Angeles

Nominating committee members

• Andres Jose Acosta, MD, PhD, Chair
• Barham K. Abu Dayyeh, MD, MPH, Mayo Clinic, Rochester, Minnesota
• Alan L. Buchman, MD, MSPH, University of Illinois at Chicago
• Octavia Pickett-Blakely, MD, MHS, Hospital of the University of Pennsylvania
• Robert Shulman, MD, Texas Children’s Hospital, Baylor College of Medicine

Pediatric Gastroenterology & Developmental Biology (PGDB)

Kelli L. VanDussen, PhDVice Chair

Cincinnati Children’s Hospital Medical Center 

Meet Our New Chair

Douglas J. Robertson, MD, MPH, AGAFAGA Institute Council Chair

VA Medical Center, White River Junction, Vermont

Geisel School of Medicine at Dartmouth, Hanover, New Hampshire

Dr. Robertson will serve as council chair for 3 years (May 2024-May 2027; DDW 2025, 2026 and 2027).

Geisel School of Medicine

Section Leadership

We are pleased to announce the results of the elections held recently by the AGA Institute Council, the driving force behind AGA’s programming at Digestive Disease Week (DDW). We welcome 8 members into their new roles as section vice chairs, joining the existing 17 Council members. Each new vice chair will serve a 2-year term that began immediately following this year’s DDW meeting and extends through DDW 2026. Following their term as vice chair, they will move into the role of section chair for an additional 2 years through DDW 2028.

AGA

We are also pleased to announce the members joining nominating committees during the 2026 nomination/election cycle. The chairs of the nominating committee will be the immediate past section chairs, whom we also recognize and thank for their service and dedication to the section and the council.
 

Basic & Clinical Intestinal Disorders (BCID)

Uma Sundaram, MDVice chair

Marshall University School of Medicine, Huntington, West Virginia

Nominating committee members

• Colleen Renee Kelly, MD, AGAF, Chair
• Amy C. Engevik, PhD, Medical University of South Carolina
• Ravinder Gill, PhD, University of Illinois at Chicago
• Madhusudan Grover, MD, Mayo Clinic, Rochester, Minnesota
• Lisa L. Strate, MD, Harborview Medical Center, Seattle

Clinical Practice (CP)

Linda Anh Nguyen, MDVice Chair

Stanford (Calif.) University School of Medicine

Nominating committee members

• Gary W. Falk, MD, MS, AGAF, Chair
• Megan Adams, MD, JD, MSc, VA Ann Arbor Healthcare System Endoscopy Unit
• Mohammad Bilal, MD, Minneapolis VA Health Care System
• Carolyn Newberry, MD, Weill Cornell Medical Center, New York
• Adam Weizman, MD, MSc, Mount Sinai Hospital, Toronto

Endoscopy, Technology & Imaging (ETI)

Vivek Kaul, MD, AGAFVice Chair

University of Rochester (N.Y.) Medical Center

Nominating committee members

• Irving Waxman, MD, Chair
• Sushovan Guha, MD, PhD, University of Texas at Houston
• Pichamol Jirapinyo, MD, MPH, Brigham and Women’s Hospital, Boston
• Vladimir Kushnir, MD, Washington University St. Louis Barnes–Jewish West County Hospital
• Andrew C. Storm, MD, Mayo Clinic, Rochester, Minnesota

Immunology, Microbiology & Inflammatory Bowel Diseases (IMIBD)

Florian Rieder, MDVice Chair

Cleveland Clinic Foundation

Nominating committee members

• Fernando S. Velayos, MD, AGAF, Chair
• Brigid S. Boland, MD, University of California, San Diego
• Karen L. Edelblum, PhD, Icahn School of Medicine at Mount Sinai, New York
• Michael Kattah, MD, PhD, UCSF Gastroenterology
• Andres J. Yarur, MD, Cedars Sinai Medical Center. Los Angeles

Liver & Biliary (LB)

Don Rockey, MDVice Chair

Medical University of South Carolina, Charleston

Nominating committee members

• Gyongyi Szabo, MD, PhD, AGAF, Chair
• Brett Fortune, MD, MSc, Montefiore Medical Center
• Ruben Hernaez, MD, MPH, PhD, Baylor College of Medicine, Houston
• Cynthia Ann Moylan, MD, MHS, MS, Duke University, Durham, North Carolina
• Douglas A. Simonetto, MD, Mayo Clinic, Rochester, Minnesota

Microbiome & Microbial Therapy (MMT)

Jessica Allegretti, MD, MPHVice Chair

Brigham and Women’s Hospital, Boston

Nominating committee members

• Purna C. Kashyap, MBBS, AGAF, Chair
• Melinda Engevik, PhD, Medical University of South Carolina
• Christian Jobin, PhD, University of Florida
• Vanessa Leone, PhD, The University of Wisconsin–Madison
• Jun Yu, MD, PhD, The Chinese University of Hong Kong

Obesity, Metabolism & Nutrition (OMN)

Berkeley M. Limketkai, MD, PhDVice Chair

University of California Los Angeles

Nominating committee members

• Andres Jose Acosta, MD, PhD, Chair
• Barham K. Abu Dayyeh, MD, MPH, Mayo Clinic, Rochester, Minnesota
• Alan L. Buchman, MD, MSPH, University of Illinois at Chicago
• Octavia Pickett-Blakely, MD, MHS, Hospital of the University of Pennsylvania
• Robert Shulman, MD, Texas Children’s Hospital, Baylor College of Medicine

Pediatric Gastroenterology & Developmental Biology (PGDB)

Kelli L. VanDussen, PhDVice Chair

Cincinnati Children’s Hospital Medical Center