In 2012, Tara Rynders’ sister was diagnosed with acute disseminated encephalomyelitis. For Ms. Rynders, a registered nurse in Denver, Colorado, the news was devastating.

“She was this beautiful 26-year-old woman, strong and healthy, and within 12 hours, she went into a coma and couldn’t move or speak,” Ms. Rynders remembered. She flew to her sister in Reno, Nevada, and moved into her intensive care unit room. The helplessness she felt wasn’t just as a sister, but as a healthcare provider.

“As a nurse, we love to fix things,” Ms. Rynders said. “But when my sister was sick, I couldn’t do anything to fix her. The doctors didn’t even know what was going on.”

When Ms. Rynders’ sister woke from the coma, she couldn’t speak. The only comfort Ms. Rynders could provide was her presence and the ability to put a smile on her sister’s face. So, Ms. Rynders did what came naturally ...

She danced.

In that tiny hospital room, she blasted her sister’s favorite song — “Party in the U.S.A.” by Miley Cyrus — and danced around the room, doing anything she could to make her sister laugh.

And this patient who could not form words found her voice.

“She’d holler so deeply, it almost sounded like she was crying,” Ms. Rynders remembered. “The depths of her grief and the depths of her joy coming out simultaneously. It was really amazing and so healing for both of us.”
 

Do You Know How Powerful Dancing Really Is?

Ms. Rynders is far from the only healthcare professional who’s discovered the healing power of dance. In recent years, doctors and nurses across the country, from Los Angeles, California, to Atlanta, Georgia; from TikTok’s “Dancing Nurse,” Cindy Jones, to Max Chiu, Nebraska’s breakdancing oncologist, have demonstrated that finding new ways to move your body isn’t just good advice for patients but could be exactly what healthcare providers need to stay mentally and physically healthy.

It comes at a time when the field faces a “mental health crisis,” according to a 2023 report from the Centers for Disease Control and Prevention. Medscape Physician Burnout & Depression Report 2024 found current rates of 49% for burnout and 20% for depression.

And medical professionals are often hesitant about seeking help. Nearly 40% of physicians reported reluctance to seek out mental health treatment over fears of professional repercussions, according to 2024 recommendations by the Mayo Clinic.

The solution? It just might be dancing.

There’s ample evidence. A 2024 study from the University of Sydney, Australia, found that dancing offers more psychological and cognitive benefits — helping with everything from depression to motivation to emotional well-being — than any other type of exercise.

Another study, published in February by The BMJ medical journal, compared the mental health benefits of everything from aerobic exercise to cognitive behavioral therapy with antidepressants and found that dance consistently offered the largest reductions in depression.

Structured dance, where you learn specific movements, can offer a huge boost to mental health, according to a 2024 University of Sydney study. But so does unchoreographed dancing, where you’re basically just letting your limbs do their own thing. A 2021 study, published in Complementary Therapies in Clinical Practice, found that 95% of dancers who just moved their bodies, regardless of how it looked to the outside world, still had huge benefits with depression, anxiety, and trauma.
 

How to Turn a Mastectomy Into a Dance Party

Deborah Cohan, MD, 55, an obstetrician at Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, discovered firsthand the power of dance back in 2013. After finding a lump in her breast during a self-exam, Dr. Cohan feared the worst. Days later, her radiologist confirmed she had invasive ductal carcinoma.

“It was a complete shock,” Dr. Cohan remembered. “I took care of myself. I ate right. I had no obvious risk factors. I did work the night shift, and there’s actually an increased risk for breast cancer among ob.gyn. workers who do night shift work. But still, it took me completely by surprise. My kids were 5 and 8 at the time, and I was terrified that they’d grow up without a mom.”

So, Dr. Cohan turned to the only thing that gave her comfort — dance class. Dancing had been an escape for Dr. Cohan since she took her first ballet class at age 3. So, she skipped work and went to her weekly Soul Motion dance class, where she found herself doing the exact opposite of escaping. She embraced her fears.

“I visualized death as a dance partner,” Dr. Cohan said. “I felt a freedom come over my body. It didn’t make sense to me at the time, but it was almost joyful. Not that I was accepting death or anticipating death, but just that I acknowledged its presence. There’s so much pressure among people with cancer to be positive. [But] that’s something that needs to come from within a person, not from outside. Nobody can dictate how someone should be feeling. And as I danced, I was genuinely feeling joy even as I recognized my own fears and didn’t turn away from them. I was experiencing all the emotions at once. It was such a relief to realize this wasn’t all going to be about sadness.”

The experience was so healing for Dr. Cohan that she decided to see if she could bring those same feelings into her bilateral mastectomy. When meeting with her surgical team, Dr. Cohan made an unorthodox request: Could her pre-op include a dance party?

“I asked the anesthesiologist in the pre-op appointment if I could dance, and he said yes,” she remembered, laughing. “And then I checked with the surgeon, and he said yes. And then I asked the perioperative nurse, and he said yes, ‘but only if you don’t make me dance, too’. So somehow it all came together.”

Dr. Cohan decided on the Beyoncé song “Get Me Bodied,” which she says resonated with her because “it’s all about being in your body and being your full self. I was like, that is exactly how I want to show up in the operating room.” The moment the music kicked in and Dr. Cohan broke into dance, all of her stress melted away.

“Even though I’d been given permission to dance, I never expected anybody else to join in,” Dr. Cohan said. But that’s exactly what they did. A friend took a video, which shows Dr. Cohan in a hospital gown and bouffant cap, dancing alongside her surgical and anesthesia teams, all of whom are dressed in scrubs, at Mount Zion Hospital in San Francisco, California.

“It’s weird to say, especially about a mastectomy,” Dr. Cohan said, “but it was one of the most joyful moments of my life.”

The video’s been viewed 8.4 million times and is so inspirational — we dare you to watch it and not want to jump out of your chair to dance — that soon others were following Dr. Cohan’s lead.

• Sixteen-year-old Amari Hall danced to celebrate her successful heart transplant.
• Ana-Alecia Ayala, a 32-year-old uterine cancer survivor, danced along to “Juju on That Beat” to make chemotherapy more tolerable.
• Doreta Norris, a patient with breast cancer, chose “Gangnam Style” to serenade her into surgery.

Bringing Dance to Other Medical Pros

Ms. Rynders realized the true power of dance years before her sister’s illness, when her mother died of cancer. “I’ve always considered myself to be very resilient as a human, but I couldn’t bounce back after my mom died,” she said. “I was nursing full time in the emergency room, and I was sad all the time. And then one day I realized, you know what brings me joy? It’s always been dance.”

She went back to school to get her Master of Fine Arts in Dance from the University of Colorado at Boulder, which she believes helped her heal. “I was actually able to grieve instead of just pretending I was okay,” she said.

Inspired by these experiences, Ms. Rynders founded The Clinic in 2017, a company that provides dance workshops for healthcare professionals struggling with burnout and secondary traumatic stress.

“I see these nurses running down hospital hallways, covered in blood from patients whose lives are literally hanging on a thread,” she said. “They’re dealing with so much stress and grief and hardship. And then to see them with us, playing and laughing — those deep belly laughs that you haven’t done since you were a kid, the deep laughing that comes from deep in your soul. It can be transformational, for them and for you.”

Ms. Rynders remembers one especially healing workshop in which the participants pretended to be astronauts in deep space, using zero gravity to inform their movements. After the exercise, a veteran hospital nurse took Ms. Rynders aside to thank her, mentioning that she was still dealing with grief for her late son, who had died from suicide years earlier.

“She had a lot of guilt around it,” Ms. Rynders remembered. “And she said to me, ‘When I went to space, I felt closer to him.’ It was just this silly little game, but it gave her this lightness that she hadn’t felt in years. She was able to be free and laugh and play and feel close to her son again.”
 

Good Medicine

Dr. Cohan, who today is cancer free, said her experience made her completely rethink her relationship with patients. She has danced with more than a few of them, though she’s careful never to force it on them. “I never want to project my idea of joy onto others,” she said. “But more than anything, it’s changed my thinking on what it means to take ownership as a patient.”

The one thing Dr. Cohan never wanted as a patient, and the thing she never wants for her own patients, is the loss of agency. “When I danced, I didn’t feel like I was just handing over my body and begrudgingly accepting what was about to happen to me,” she said. “I was taking ownership around my decision, and I felt connected, really connected, to my surgical team.”

As a patient, Dr. Cohan experienced what she calls the “regimented” atmosphere of medicine. “You’re told where to go, what to do, and you have no control over any of it,” recalled Dr. Cohan, who’s now semiretired and runs retreats for women with breast cancer. “But by bringing in dance, it felt really radical that my healthcare team was doing my thing, not the other way around.”
 

(Re)Learning to Move More Consciously

Healthcare providers need these moments of escape just as much as patients living with disease. The difference is, as Ms. Rynders points out, those in the medical field aren’t always as aware of their emotional distress. “I think if you ask a nurse, ‘How can I help you? What do you need?’ They’re usually like, ‘I don’t know. I don’t even know what I need,’ ” Ms. Rynders said. “Even if they did know what they needed, I think it’s hard to ask for it and even harder to receive it.”

At Ms. Rynders’ workshops, not everybody is comfortable dancing, of course. So, new participants are always given the option just to witness, to be in the room and watch what happens. “But I also really encourage people to take advantage of this opportunity to do something different and disrupt the way we live on a daily basis,” Ms. Rynders said. “Let your brain try something new and be courageous. We’ve only had a few people who sat on the sidelines the whole time.”

It’s not always just about feelings, Dr. Cohan added, but physical relaxation. “Sometimes it’s just about remembering how to move consciously. When I was having surgery, I didn’t just dance to relax myself. I wanted my entire surgical team to be relaxed.”

For Ms. Rynders, every time she dances with her patients, or with fellow healthcare workers, she’s reminded of her sister and the comfort she was able to give her when no amount of medicine would make things better.

“We don’t always need to be fixed by things,” she said. “Sometimes we just need to be present with one another and be with each other. And sometimes, the best way to do that is by dancing till the tears roll down your cheeks.”
 

A version of this article appeared on Medscape.com.

In 2012, Tara Rynders’ sister was diagnosed with acute disseminated encephalomyelitis. For Ms. Rynders, a registered nurse in Denver, Colorado, the news was devastating.

“She was this beautiful 26-year-old woman, strong and healthy, and within 12 hours, she went into a coma and couldn’t move or speak,” Ms. Rynders remembered. She flew to her sister in Reno, Nevada, and moved into her intensive care unit room. The helplessness she felt wasn’t just as a sister, but as a healthcare provider.

“As a nurse, we love to fix things,” Ms. Rynders said. “But when my sister was sick, I couldn’t do anything to fix her. The doctors didn’t even know what was going on.”

When Ms. Rynders’ sister woke from the coma, she couldn’t speak. The only comfort Ms. Rynders could provide was her presence and the ability to put a smile on her sister’s face. So, Ms. Rynders did what came naturally ...

She danced.

In that tiny hospital room, she blasted her sister’s favorite song — “Party in the U.S.A.” by Miley Cyrus — and danced around the room, doing anything she could to make her sister laugh.

And this patient who could not form words found her voice.

“She’d holler so deeply, it almost sounded like she was crying,” Ms. Rynders remembered. “The depths of her grief and the depths of her joy coming out simultaneously. It was really amazing and so healing for both of us.”
 

Do You Know How Powerful Dancing Really Is?

Ms. Rynders is far from the only healthcare professional who’s discovered the healing power of dance. In recent years, doctors and nurses across the country, from Los Angeles, California, to Atlanta, Georgia; from TikTok’s “Dancing Nurse,” Cindy Jones, to Max Chiu, Nebraska’s breakdancing oncologist, have demonstrated that finding new ways to move your body isn’t just good advice for patients but could be exactly what healthcare providers need to stay mentally and physically healthy.

It comes at a time when the field faces a “mental health crisis,” according to a 2023 report from the Centers for Disease Control and Prevention. Medscape Physician Burnout & Depression Report 2024 found current rates of 49% for burnout and 20% for depression.

And medical professionals are often hesitant about seeking help. Nearly 40% of physicians reported reluctance to seek out mental health treatment over fears of professional repercussions, according to 2024 recommendations by the Mayo Clinic.

The solution? It just might be dancing.

There’s ample evidence. A 2024 study from the University of Sydney, Australia, found that dancing offers more psychological and cognitive benefits — helping with everything from depression to motivation to emotional well-being — than any other type of exercise.

Another study, published in February by The BMJ medical journal, compared the mental health benefits of everything from aerobic exercise to cognitive behavioral therapy with antidepressants and found that dance consistently offered the largest reductions in depression.

Structured dance, where you learn specific movements, can offer a huge boost to mental health, according to a 2024 University of Sydney study. But so does unchoreographed dancing, where you’re basically just letting your limbs do their own thing. A 2021 study, published in Complementary Therapies in Clinical Practice, found that 95% of dancers who just moved their bodies, regardless of how it looked to the outside world, still had huge benefits with depression, anxiety, and trauma.
 

How to Turn a Mastectomy Into a Dance Party

Deborah Cohan, MD, 55, an obstetrician at Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, discovered firsthand the power of dance back in 2013. After finding a lump in her breast during a self-exam, Dr. Cohan feared the worst. Days later, her radiologist confirmed she had invasive ductal carcinoma.

“It was a complete shock,” Dr. Cohan remembered. “I took care of myself. I ate right. I had no obvious risk factors. I did work the night shift, and there’s actually an increased risk for breast cancer among ob.gyn. workers who do night shift work. But still, it took me completely by surprise. My kids were 5 and 8 at the time, and I was terrified that they’d grow up without a mom.”

So, Dr. Cohan turned to the only thing that gave her comfort — dance class. Dancing had been an escape for Dr. Cohan since she took her first ballet class at age 3. So, she skipped work and went to her weekly Soul Motion dance class, where she found herself doing the exact opposite of escaping. She embraced her fears.

“I visualized death as a dance partner,” Dr. Cohan said. “I felt a freedom come over my body. It didn’t make sense to me at the time, but it was almost joyful. Not that I was accepting death or anticipating death, but just that I acknowledged its presence. There’s so much pressure among people with cancer to be positive. [But] that’s something that needs to come from within a person, not from outside. Nobody can dictate how someone should be feeling. And as I danced, I was genuinely feeling joy even as I recognized my own fears and didn’t turn away from them. I was experiencing all the emotions at once. It was such a relief to realize this wasn’t all going to be about sadness.”

The experience was so healing for Dr. Cohan that she decided to see if she could bring those same feelings into her bilateral mastectomy. When meeting with her surgical team, Dr. Cohan made an unorthodox request: Could her pre-op include a dance party?

“I asked the anesthesiologist in the pre-op appointment if I could dance, and he said yes,” she remembered, laughing. “And then I checked with the surgeon, and he said yes. And then I asked the perioperative nurse, and he said yes, ‘but only if you don’t make me dance, too’. So somehow it all came together.”

Dr. Cohan decided on the Beyoncé song “Get Me Bodied,” which she says resonated with her because “it’s all about being in your body and being your full self. I was like, that is exactly how I want to show up in the operating room.” The moment the music kicked in and Dr. Cohan broke into dance, all of her stress melted away.

“Even though I’d been given permission to dance, I never expected anybody else to join in,” Dr. Cohan said. But that’s exactly what they did. A friend took a video, which shows Dr. Cohan in a hospital gown and bouffant cap, dancing alongside her surgical and anesthesia teams, all of whom are dressed in scrubs, at Mount Zion Hospital in San Francisco, California.

“It’s weird to say, especially about a mastectomy,” Dr. Cohan said, “but it was one of the most joyful moments of my life.”

The video’s been viewed 8.4 million times and is so inspirational — we dare you to watch it and not want to jump out of your chair to dance — that soon others were following Dr. Cohan’s lead.

• Sixteen-year-old Amari Hall danced to celebrate her successful heart transplant.
• Ana-Alecia Ayala, a 32-year-old uterine cancer survivor, danced along to “Juju on That Beat” to make chemotherapy more tolerable.
• Doreta Norris, a patient with breast cancer, chose “Gangnam Style” to serenade her into surgery.

Bringing Dance to Other Medical Pros

Ms. Rynders realized the true power of dance years before her sister’s illness, when her mother died of cancer. “I’ve always considered myself to be very resilient as a human, but I couldn’t bounce back after my mom died,” she said. “I was nursing full time in the emergency room, and I was sad all the time. And then one day I realized, you know what brings me joy? It’s always been dance.”

She went back to school to get her Master of Fine Arts in Dance from the University of Colorado at Boulder, which she believes helped her heal. “I was actually able to grieve instead of just pretending I was okay,” she said.

Inspired by these experiences, Ms. Rynders founded The Clinic in 2017, a company that provides dance workshops for healthcare professionals struggling with burnout and secondary traumatic stress.

“I see these nurses running down hospital hallways, covered in blood from patients whose lives are literally hanging on a thread,” she said. “They’re dealing with so much stress and grief and hardship. And then to see them with us, playing and laughing — those deep belly laughs that you haven’t done since you were a kid, the deep laughing that comes from deep in your soul. It can be transformational, for them and for you.”

Ms. Rynders remembers one especially healing workshop in which the participants pretended to be astronauts in deep space, using zero gravity to inform their movements. After the exercise, a veteran hospital nurse took Ms. Rynders aside to thank her, mentioning that she was still dealing with grief for her late son, who had died from suicide years earlier.

“She had a lot of guilt around it,” Ms. Rynders remembered. “And she said to me, ‘When I went to space, I felt closer to him.’ It was just this silly little game, but it gave her this lightness that she hadn’t felt in years. She was able to be free and laugh and play and feel close to her son again.”
 

Good Medicine

Dr. Cohan, who today is cancer free, said her experience made her completely rethink her relationship with patients. She has danced with more than a few of them, though she’s careful never to force it on them. “I never want to project my idea of joy onto others,” she said. “But more than anything, it’s changed my thinking on what it means to take ownership as a patient.”

The one thing Dr. Cohan never wanted as a patient, and the thing she never wants for her own patients, is the loss of agency. “When I danced, I didn’t feel like I was just handing over my body and begrudgingly accepting what was about to happen to me,” she said. “I was taking ownership around my decision, and I felt connected, really connected, to my surgical team.”

As a patient, Dr. Cohan experienced what she calls the “regimented” atmosphere of medicine. “You’re told where to go, what to do, and you have no control over any of it,” recalled Dr. Cohan, who’s now semiretired and runs retreats for women with breast cancer. “But by bringing in dance, it felt really radical that my healthcare team was doing my thing, not the other way around.”
 

(Re)Learning to Move More Consciously

Healthcare providers need these moments of escape just as much as patients living with disease. The difference is, as Ms. Rynders points out, those in the medical field aren’t always as aware of their emotional distress. “I think if you ask a nurse, ‘How can I help you? What do you need?’ They’re usually like, ‘I don’t know. I don’t even know what I need,’ ” Ms. Rynders said. “Even if they did know what they needed, I think it’s hard to ask for it and even harder to receive it.”

At Ms. Rynders’ workshops, not everybody is comfortable dancing, of course. So, new participants are always given the option just to witness, to be in the room and watch what happens. “But I also really encourage people to take advantage of this opportunity to do something different and disrupt the way we live on a daily basis,” Ms. Rynders said. “Let your brain try something new and be courageous. We’ve only had a few people who sat on the sidelines the whole time.”

It’s not always just about feelings, Dr. Cohan added, but physical relaxation. “Sometimes it’s just about remembering how to move consciously. When I was having surgery, I didn’t just dance to relax myself. I wanted my entire surgical team to be relaxed.”

For Ms. Rynders, every time she dances with her patients, or with fellow healthcare workers, she’s reminded of her sister and the comfort she was able to give her when no amount of medicine would make things better.

“We don’t always need to be fixed by things,” she said. “Sometimes we just need to be present with one another and be with each other. And sometimes, the best way to do that is by dancing till the tears roll down your cheeks.”
 

A version of this article appeared on Medscape.com.

In 2012, Tara Rynders’ sister was diagnosed with acute disseminated encephalomyelitis. For Ms. Rynders, a registered nurse in Denver, Colorado, the news was devastating.

“She was this beautiful 26-year-old woman, strong and healthy, and within 12 hours, she went into a coma and couldn’t move or speak,” Ms. Rynders remembered. She flew to her sister in Reno, Nevada, and moved into her intensive care unit room. The helplessness she felt wasn’t just as a sister, but as a healthcare provider.

“As a nurse, we love to fix things,” Ms. Rynders said. “But when my sister was sick, I couldn’t do anything to fix her. The doctors didn’t even know what was going on.”

When Ms. Rynders’ sister woke from the coma, she couldn’t speak. The only comfort Ms. Rynders could provide was her presence and the ability to put a smile on her sister’s face. So, Ms. Rynders did what came naturally ...

She danced.

In that tiny hospital room, she blasted her sister’s favorite song — “Party in the U.S.A.” by Miley Cyrus — and danced around the room, doing anything she could to make her sister laugh.

And this patient who could not form words found her voice.

“She’d holler so deeply, it almost sounded like she was crying,” Ms. Rynders remembered. “The depths of her grief and the depths of her joy coming out simultaneously. It was really amazing and so healing for both of us.”
 

Do You Know How Powerful Dancing Really Is?

Ms. Rynders is far from the only healthcare professional who’s discovered the healing power of dance. In recent years, doctors and nurses across the country, from Los Angeles, California, to Atlanta, Georgia; from TikTok’s “Dancing Nurse,” Cindy Jones, to Max Chiu, Nebraska’s breakdancing oncologist, have demonstrated that finding new ways to move your body isn’t just good advice for patients but could be exactly what healthcare providers need to stay mentally and physically healthy.

It comes at a time when the field faces a “mental health crisis,” according to a 2023 report from the Centers for Disease Control and Prevention. Medscape Physician Burnout & Depression Report 2024 found current rates of 49% for burnout and 20% for depression.

And medical professionals are often hesitant about seeking help. Nearly 40% of physicians reported reluctance to seek out mental health treatment over fears of professional repercussions, according to 2024 recommendations by the Mayo Clinic.

The solution? It just might be dancing.

There’s ample evidence. A 2024 study from the University of Sydney, Australia, found that dancing offers more psychological and cognitive benefits — helping with everything from depression to motivation to emotional well-being — than any other type of exercise.

Another study, published in February by The BMJ medical journal, compared the mental health benefits of everything from aerobic exercise to cognitive behavioral therapy with antidepressants and found that dance consistently offered the largest reductions in depression.

Structured dance, where you learn specific movements, can offer a huge boost to mental health, according to a 2024 University of Sydney study. But so does unchoreographed dancing, where you’re basically just letting your limbs do their own thing. A 2021 study, published in Complementary Therapies in Clinical Practice, found that 95% of dancers who just moved their bodies, regardless of how it looked to the outside world, still had huge benefits with depression, anxiety, and trauma.
 

How to Turn a Mastectomy Into a Dance Party

Deborah Cohan, MD, 55, an obstetrician at Zuckerberg San Francisco General Hospital and Trauma Center, San Francisco, California, discovered firsthand the power of dance back in 2013. After finding a lump in her breast during a self-exam, Dr. Cohan feared the worst. Days later, her radiologist confirmed she had invasive ductal carcinoma.

“It was a complete shock,” Dr. Cohan remembered. “I took care of myself. I ate right. I had no obvious risk factors. I did work the night shift, and there’s actually an increased risk for breast cancer among ob.gyn. workers who do night shift work. But still, it took me completely by surprise. My kids were 5 and 8 at the time, and I was terrified that they’d grow up without a mom.”

So, Dr. Cohan turned to the only thing that gave her comfort — dance class. Dancing had been an escape for Dr. Cohan since she took her first ballet class at age 3. So, she skipped work and went to her weekly Soul Motion dance class, where she found herself doing the exact opposite of escaping. She embraced her fears.

“I visualized death as a dance partner,” Dr. Cohan said. “I felt a freedom come over my body. It didn’t make sense to me at the time, but it was almost joyful. Not that I was accepting death or anticipating death, but just that I acknowledged its presence. There’s so much pressure among people with cancer to be positive. [But] that’s something that needs to come from within a person, not from outside. Nobody can dictate how someone should be feeling. And as I danced, I was genuinely feeling joy even as I recognized my own fears and didn’t turn away from them. I was experiencing all the emotions at once. It was such a relief to realize this wasn’t all going to be about sadness.”

The experience was so healing for Dr. Cohan that she decided to see if she could bring those same feelings into her bilateral mastectomy. When meeting with her surgical team, Dr. Cohan made an unorthodox request: Could her pre-op include a dance party?

“I asked the anesthesiologist in the pre-op appointment if I could dance, and he said yes,” she remembered, laughing. “And then I checked with the surgeon, and he said yes. And then I asked the perioperative nurse, and he said yes, ‘but only if you don’t make me dance, too’. So somehow it all came together.”

Dr. Cohan decided on the Beyoncé song “Get Me Bodied,” which she says resonated with her because “it’s all about being in your body and being your full self. I was like, that is exactly how I want to show up in the operating room.” The moment the music kicked in and Dr. Cohan broke into dance, all of her stress melted away.

“Even though I’d been given permission to dance, I never expected anybody else to join in,” Dr. Cohan said. But that’s exactly what they did. A friend took a video, which shows Dr. Cohan in a hospital gown and bouffant cap, dancing alongside her surgical and anesthesia teams, all of whom are dressed in scrubs, at Mount Zion Hospital in San Francisco, California.

“It’s weird to say, especially about a mastectomy,” Dr. Cohan said, “but it was one of the most joyful moments of my life.”

The video’s been viewed 8.4 million times and is so inspirational — we dare you to watch it and not want to jump out of your chair to dance — that soon others were following Dr. Cohan’s lead.

• Sixteen-year-old Amari Hall danced to celebrate her successful heart transplant.
• Ana-Alecia Ayala, a 32-year-old uterine cancer survivor, danced along to “Juju on That Beat” to make chemotherapy more tolerable.
• Doreta Norris, a patient with breast cancer, chose “Gangnam Style” to serenade her into surgery.

Bringing Dance to Other Medical Pros

Ms. Rynders realized the true power of dance years before her sister’s illness, when her mother died of cancer. “I’ve always considered myself to be very resilient as a human, but I couldn’t bounce back after my mom died,” she said. “I was nursing full time in the emergency room, and I was sad all the time. And then one day I realized, you know what brings me joy? It’s always been dance.”

She went back to school to get her Master of Fine Arts in Dance from the University of Colorado at Boulder, which she believes helped her heal. “I was actually able to grieve instead of just pretending I was okay,” she said.

Inspired by these experiences, Ms. Rynders founded The Clinic in 2017, a company that provides dance workshops for healthcare professionals struggling with burnout and secondary traumatic stress.

“I see these nurses running down hospital hallways, covered in blood from patients whose lives are literally hanging on a thread,” she said. “They’re dealing with so much stress and grief and hardship. And then to see them with us, playing and laughing — those deep belly laughs that you haven’t done since you were a kid, the deep laughing that comes from deep in your soul. It can be transformational, for them and for you.”

Ms. Rynders remembers one especially healing workshop in which the participants pretended to be astronauts in deep space, using zero gravity to inform their movements. After the exercise, a veteran hospital nurse took Ms. Rynders aside to thank her, mentioning that she was still dealing with grief for her late son, who had died from suicide years earlier.

“She had a lot of guilt around it,” Ms. Rynders remembered. “And she said to me, ‘When I went to space, I felt closer to him.’ It was just this silly little game, but it gave her this lightness that she hadn’t felt in years. She was able to be free and laugh and play and feel close to her son again.”
 

Good Medicine

Dr. Cohan, who today is cancer free, said her experience made her completely rethink her relationship with patients. She has danced with more than a few of them, though she’s careful never to force it on them. “I never want to project my idea of joy onto others,” she said. “But more than anything, it’s changed my thinking on what it means to take ownership as a patient.”

The one thing Dr. Cohan never wanted as a patient, and the thing she never wants for her own patients, is the loss of agency. “When I danced, I didn’t feel like I was just handing over my body and begrudgingly accepting what was about to happen to me,” she said. “I was taking ownership around my decision, and I felt connected, really connected, to my surgical team.”

As a patient, Dr. Cohan experienced what she calls the “regimented” atmosphere of medicine. “You’re told where to go, what to do, and you have no control over any of it,” recalled Dr. Cohan, who’s now semiretired and runs retreats for women with breast cancer. “But by bringing in dance, it felt really radical that my healthcare team was doing my thing, not the other way around.”
 

(Re)Learning to Move More Consciously

Healthcare providers need these moments of escape just as much as patients living with disease. The difference is, as Ms. Rynders points out, those in the medical field aren’t always as aware of their emotional distress. “I think if you ask a nurse, ‘How can I help you? What do you need?’ They’re usually like, ‘I don’t know. I don’t even know what I need,’ ” Ms. Rynders said. “Even if they did know what they needed, I think it’s hard to ask for it and even harder to receive it.”

At Ms. Rynders’ workshops, not everybody is comfortable dancing, of course. So, new participants are always given the option just to witness, to be in the room and watch what happens. “But I also really encourage people to take advantage of this opportunity to do something different and disrupt the way we live on a daily basis,” Ms. Rynders said. “Let your brain try something new and be courageous. We’ve only had a few people who sat on the sidelines the whole time.”

It’s not always just about feelings, Dr. Cohan added, but physical relaxation. “Sometimes it’s just about remembering how to move consciously. When I was having surgery, I didn’t just dance to relax myself. I wanted my entire surgical team to be relaxed.”

For Ms. Rynders, every time she dances with her patients, or with fellow healthcare workers, she’s reminded of her sister and the comfort she was able to give her when no amount of medicine would make things better.

“We don’t always need to be fixed by things,” she said. “Sometimes we just need to be present with one another and be with each other. And sometimes, the best way to do that is by dancing till the tears roll down your cheeks.”
 

A version of this article appeared on Medscape.com.

Use of a modified sleep apnea index can identify cardiovascular risk factors in adults with moderate to severe obstructive sleep apnea (OSA), according to results from a new study presented at the American Academy of Otolaryngology–Head and Neck Surgery 2024 Annual Meeting.

The modified sleep apnea severity index (mSASI) combines patient anatomy, weight, sleep study metrics, and symptoms, to provide a more nuanced measure of OSA than the standard apnea-hypopnea index (AHI), said Jennifer A. Goldfarb, MHS, a medical student at Thomas Jefferson University, Philadelphia, Pennsylvania, who presented the findings.

OSA has an association with many negative cardiovascular comorbidities; however, “the AHI provides only a single metric and does not provide a holistic assessment of the individual patient’s disease severity,” said senior author Colin T. Huntley, MD, also of Thomas Jefferson University. 

“OSA is very complex, and having a robust system to assess the disease may be a better predictor of overall severity,” he told this news organization. 

Previous research has shown a correlation between mSASI and mean arterial pressure and serum C-reactive protein in OSA patients, but the connection with cardiovascular risk factors has not been well studied, Ms. Goldfarb noted. 

In the retrospective cohort study, Ms. Goldfarb and colleagues looked at mSASI scores from 260 CPAP-intolerant patients with OSA who underwent upper airway stimulation, maxillomandibular advancement, or expansion sphincter pharyngoplasty at a single sleep surgery clinic between 2014 and 2021. The mSASI uses a score of 1-3, with 3 as the highest level of OSA severity.

Cardiovascular risk factors were assessed at the patient’s initial evaluation by the sleep surgery team. They included coronary artery disease, type 2 diabetes, atrial fibrillation, congestive heart failure, hypertension, and cerebrovascular accident. 

A total of 142 patients (55%) had an mSASI of 1; 91 (35%) had an mSASI of 2; and 27 (10%) had an mSASI of 3. At least one cardiovascular risk factor was present in 58%, 68%, and 63% of these groups, respectively (P = .3). 

Stratifying participants by mSASI scores, the researchers found that patients with an mSASI of 2 or 3 were significantly more likely than those with an mSASI of 1 to have more cardiovascular risk factors on initial presentation, and were significantly more likely to be diagnosed with hypertension (P = .02 for both). 

Using the AHI, however, patients with moderate to severe OSA (AHI > 15) had a similar number of cardiovascular risk factors as those with mild OSA (P > .05). 

“A higher mSASI score, which represents worse disease, was associated with a higher Framingham risk score, which supported our hypothesis; however, the AHI was not found to be associated with an increased Framingham score,” Dr. Huntley told this news organization.
 

Takeaways and Next Steps

These results suggest that the AHI, while a good metric, might not be the best tool for assessment of overall disease severity, given the complexity of OSA, the impact of the disease on patient quality of life, and the risk for downstream cardiovascular disease, said Dr. Huntley. 

The findings were limited by the retrospective design and use of data from a single center. 

Population-level data are needed to identify variables that may be meaningful to create a future tool that provides the best picture of the individual patient’s disease, he added. Additional prospective data are also needed to assess the impact of the scoring system on long-term treatment outcomes. 

“The current study is especially interesting as we are just beginning to understand the factors that predict cardiovascular risk for patients with obstructive sleep apnea,” Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“For a long time, we primarily looked at the AHI and/or oxygen levels during sleep as risk factors, and we haven’t looked as much at other factors.” said Dr. Durr, who served as a moderator for the session in which the study was presented.

The current findings provide a more comprehensive look at cardiovascular risk; the inclusion of patient anatomy and symptoms add to the knowledge of this topic, and will lead to further work in this area, she added. 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Huntley disclosed receiving research support from Nyxoah and Inspire, and serving as a consultant for Nyxoah, Inspire, and Avivomed. 

Dr. Durr had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

Use of a modified sleep apnea index can identify cardiovascular risk factors in adults with moderate to severe obstructive sleep apnea (OSA), according to results from a new study presented at the American Academy of Otolaryngology–Head and Neck Surgery 2024 Annual Meeting.

The modified sleep apnea severity index (mSASI) combines patient anatomy, weight, sleep study metrics, and symptoms, to provide a more nuanced measure of OSA than the standard apnea-hypopnea index (AHI), said Jennifer A. Goldfarb, MHS, a medical student at Thomas Jefferson University, Philadelphia, Pennsylvania, who presented the findings.

OSA has an association with many negative cardiovascular comorbidities; however, “the AHI provides only a single metric and does not provide a holistic assessment of the individual patient’s disease severity,” said senior author Colin T. Huntley, MD, also of Thomas Jefferson University. 

“OSA is very complex, and having a robust system to assess the disease may be a better predictor of overall severity,” he told this news organization. 

Previous research has shown a correlation between mSASI and mean arterial pressure and serum C-reactive protein in OSA patients, but the connection with cardiovascular risk factors has not been well studied, Ms. Goldfarb noted. 

In the retrospective cohort study, Ms. Goldfarb and colleagues looked at mSASI scores from 260 CPAP-intolerant patients with OSA who underwent upper airway stimulation, maxillomandibular advancement, or expansion sphincter pharyngoplasty at a single sleep surgery clinic between 2014 and 2021. The mSASI uses a score of 1-3, with 3 as the highest level of OSA severity.

Cardiovascular risk factors were assessed at the patient’s initial evaluation by the sleep surgery team. They included coronary artery disease, type 2 diabetes, atrial fibrillation, congestive heart failure, hypertension, and cerebrovascular accident. 

A total of 142 patients (55%) had an mSASI of 1; 91 (35%) had an mSASI of 2; and 27 (10%) had an mSASI of 3. At least one cardiovascular risk factor was present in 58%, 68%, and 63% of these groups, respectively (P = .3). 

Stratifying participants by mSASI scores, the researchers found that patients with an mSASI of 2 or 3 were significantly more likely than those with an mSASI of 1 to have more cardiovascular risk factors on initial presentation, and were significantly more likely to be diagnosed with hypertension (P = .02 for both). 

Using the AHI, however, patients with moderate to severe OSA (AHI > 15) had a similar number of cardiovascular risk factors as those with mild OSA (P > .05). 

“A higher mSASI score, which represents worse disease, was associated with a higher Framingham risk score, which supported our hypothesis; however, the AHI was not found to be associated with an increased Framingham score,” Dr. Huntley told this news organization.
 

Takeaways and Next Steps

These results suggest that the AHI, while a good metric, might not be the best tool for assessment of overall disease severity, given the complexity of OSA, the impact of the disease on patient quality of life, and the risk for downstream cardiovascular disease, said Dr. Huntley. 

The findings were limited by the retrospective design and use of data from a single center. 

Population-level data are needed to identify variables that may be meaningful to create a future tool that provides the best picture of the individual patient’s disease, he added. Additional prospective data are also needed to assess the impact of the scoring system on long-term treatment outcomes. 

“The current study is especially interesting as we are just beginning to understand the factors that predict cardiovascular risk for patients with obstructive sleep apnea,” Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“For a long time, we primarily looked at the AHI and/or oxygen levels during sleep as risk factors, and we haven’t looked as much at other factors.” said Dr. Durr, who served as a moderator for the session in which the study was presented.

The current findings provide a more comprehensive look at cardiovascular risk; the inclusion of patient anatomy and symptoms add to the knowledge of this topic, and will lead to further work in this area, she added. 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Huntley disclosed receiving research support from Nyxoah and Inspire, and serving as a consultant for Nyxoah, Inspire, and Avivomed. 

Dr. Durr had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

Use of a modified sleep apnea index can identify cardiovascular risk factors in adults with moderate to severe obstructive sleep apnea (OSA), according to results from a new study presented at the American Academy of Otolaryngology–Head and Neck Surgery 2024 Annual Meeting.

The modified sleep apnea severity index (mSASI) combines patient anatomy, weight, sleep study metrics, and symptoms, to provide a more nuanced measure of OSA than the standard apnea-hypopnea index (AHI), said Jennifer A. Goldfarb, MHS, a medical student at Thomas Jefferson University, Philadelphia, Pennsylvania, who presented the findings.

OSA has an association with many negative cardiovascular comorbidities; however, “the AHI provides only a single metric and does not provide a holistic assessment of the individual patient’s disease severity,” said senior author Colin T. Huntley, MD, also of Thomas Jefferson University. 

“OSA is very complex, and having a robust system to assess the disease may be a better predictor of overall severity,” he told this news organization. 

Previous research has shown a correlation between mSASI and mean arterial pressure and serum C-reactive protein in OSA patients, but the connection with cardiovascular risk factors has not been well studied, Ms. Goldfarb noted. 

In the retrospective cohort study, Ms. Goldfarb and colleagues looked at mSASI scores from 260 CPAP-intolerant patients with OSA who underwent upper airway stimulation, maxillomandibular advancement, or expansion sphincter pharyngoplasty at a single sleep surgery clinic between 2014 and 2021. The mSASI uses a score of 1-3, with 3 as the highest level of OSA severity.

Cardiovascular risk factors were assessed at the patient’s initial evaluation by the sleep surgery team. They included coronary artery disease, type 2 diabetes, atrial fibrillation, congestive heart failure, hypertension, and cerebrovascular accident. 

A total of 142 patients (55%) had an mSASI of 1; 91 (35%) had an mSASI of 2; and 27 (10%) had an mSASI of 3. At least one cardiovascular risk factor was present in 58%, 68%, and 63% of these groups, respectively (P = .3). 

Stratifying participants by mSASI scores, the researchers found that patients with an mSASI of 2 or 3 were significantly more likely than those with an mSASI of 1 to have more cardiovascular risk factors on initial presentation, and were significantly more likely to be diagnosed with hypertension (P = .02 for both). 

Using the AHI, however, patients with moderate to severe OSA (AHI > 15) had a similar number of cardiovascular risk factors as those with mild OSA (P > .05). 

“A higher mSASI score, which represents worse disease, was associated with a higher Framingham risk score, which supported our hypothesis; however, the AHI was not found to be associated with an increased Framingham score,” Dr. Huntley told this news organization.
 

Takeaways and Next Steps

These results suggest that the AHI, while a good metric, might not be the best tool for assessment of overall disease severity, given the complexity of OSA, the impact of the disease on patient quality of life, and the risk for downstream cardiovascular disease, said Dr. Huntley. 

The findings were limited by the retrospective design and use of data from a single center. 

Population-level data are needed to identify variables that may be meaningful to create a future tool that provides the best picture of the individual patient’s disease, he added. Additional prospective data are also needed to assess the impact of the scoring system on long-term treatment outcomes. 

“The current study is especially interesting as we are just beginning to understand the factors that predict cardiovascular risk for patients with obstructive sleep apnea,” Megan Durr, MD, of the University of California, San Francisco, said in an interview.

“For a long time, we primarily looked at the AHI and/or oxygen levels during sleep as risk factors, and we haven’t looked as much at other factors.” said Dr. Durr, who served as a moderator for the session in which the study was presented.

The current findings provide a more comprehensive look at cardiovascular risk; the inclusion of patient anatomy and symptoms add to the knowledge of this topic, and will lead to further work in this area, she added. 

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Huntley disclosed receiving research support from Nyxoah and Inspire, and serving as a consultant for Nyxoah, Inspire, and Avivomed. 

Dr. Durr had no financial conflicts to disclose. 
 

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

Common complaints of abdominal pain, fever, shortness of breath, or rash can signal more serious disease that should be referred to specialty care or might be related to benign conditions.

Combine the vague nature of many patients’ descriptions and the pressure of short visits, and clinicians have a recipe for all manner of diagnostic error.

An estimated 5% of US adults who seek outpatient care each year experience a diagnostic error. Most Americans will eventually have this experience, according to a 2015 report from the National Academy of Medicine.

The most frequently missed diagnoses in primary care involve conditions such as pneumonia, decompensated heart failure, acute renal failure, cancer, urinary tract infection, and pyelonephritis.

“It’s not one or two or three types of diagnosis that are missed: We miss a lot of things, especially in primary care,” said Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey VA Medical Center and the Baylor College of Medicine in Houston, Texas.

One of the most serious errors is to miss cancer, with failing to follow‐up on abnormal tests ranking consistently as one of the leading causes of malpractice claims. But most diagnostic errors do not lead to lawsuits, although they often result in missed and delayed opportunities for patients to get needed care.

In interviews with this news organization, experts who have studied the root causes of diagnostic error suggested primary care clinicians focus on several practices to avoid mistakes: Ask questions with humility and curiosity, use checklists, and brainstorm with patients the potential root cause of symptoms.
 

Humility and Curiosity 

Clinicians should remain aware of the potential for errors and reach out for assistance when needed, keeping an open mind that common symptoms may, in rare cases, signal serious illness, Dr. Singh said.

Dr. Singh recommends continual review with what he calls “byte-sized” learning through digital tools such as the Human Diagnosis app and podcasts and webinars offered by Clinical Problem Solvers.

Continuing education activities such as classes for Maintenance of Certification (MOC) can help keep physicians up to date and alert for cases where seemingly common symptoms may turn out to be something serious, said Richard M. Wardrop, III, MD, PhD, an internal medicine physician at the Cleveland Clinic in Ohio, and chair of the internal medicine board at the American Board of Internal Medicine.

“I’ve been in practice for 20 years. I’m double board certified in peds and medicine, and I regularly teach students and residents and mentor other physicians, but the further I go in my career and in practice, the more humble I become,” Dr. Wardrop told this news organization.

He said he recently spent a few hours on MOC for pediatrics and found the review was helpful in his practice in medicine.

“If I find myself taking care of a patient in a newborn nursery anytime soon, I’m going to understand the new hyperbilirubinemia guidelines,” Dr. Wardrop said. “That takes time and energy, but when I was done with the questions for this quarter, I felt good about myself.”
 

Checking It Twice

Clinicians should incorporate checklists into daily practice. Reviewing these with patients can not only help rule out an illness but also serve as a nonconfrontational method to inquire about issues patients may find uncomfortable, said John Ely, MD, MSPH, professor emeritus of family medicine at the University of Iowa Carver College of Medicine in Iowa City.

Clinicians could benefit from the approach used in aviation, where checklists are a required and routine part of a pilot’s job, Dr. Ely said.

Although clinicians may assume patients expect them to work from memory and knowledge without this aide, many will see using a checklist as a sign of providing thorough care, he said.

Checklists can also open a pathway for discussions about potentially difficult or touchy issues in short visits. For example, a patient might feel defensive if a clinician asks about depression during a visit for abdominal pain. But incorporating a question in a checklist allows for a different framing of the question.

“A clinician could say ‘I didn’t say you were depressed because of your abdominal pain, I brought it up because it’s on the list,’” Dr. Ely said. The checklist is “a very easy way to bring up those things.”

Dr. Ely said he has cared for a few patients who sought help for abdominal pain that turned out to be linked to sexual abuse in their past. Dr. Ely used a checklist with these patients to review possible causes for their illness. He recalled one of these patients who had suffered sexual abuse and had depression, neither of which was readily apparent.

“There was nothing about her affect that appeared to be depressed, and she had seen multiple physicians unable to make a diagnosis,” Dr. Ely said. “She had worked up for multiple other diseases and this had never come up before.”
 

Cooperation 

“Coproduction” is how Kathryn McDonald, PhD, describes an ideal path to getting an accurate diagnosis. The intent is for clinicians to enlist patients in helping them in finding the root cause of symptoms.

“It’s bringing the patient into knowing that they are in a partnership to coproduce, knowing that there is a process going on,” said Dr. McDonald, who is codirector of the Armstrong Institute Center for Diagnostic Excellence at Johns Hopkins University in Baltimore, Maryland.

In many cases, patients seek reassurance for ruling out a suspected condition, which the physician can sometimes provide. In others, clinicians may not be able to offer a concrete diagnosis.

“There are times when uncertainty is more pervasive and I will ask patients, ‘Let’s brainstorm this together,’” Dr. Wardrop said.

A version of this article appeared on Medscape.com.

MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.

If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.

The study was presented at the 37th European College of Neuropsychopharmacology Congress.
 

Differences in Brain Activity

During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.

The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.

To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.

The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.

All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.

This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”

Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.

“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”

Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.

If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.

“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.

Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.

“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.

The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.

If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.

The study was presented at the 37th European College of Neuropsychopharmacology Congress.
 

Differences in Brain Activity

During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.

The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.

To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.

The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.

All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.

This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”

Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.

“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”

Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.

If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.

“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.

Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.

“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.

The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.

A version of this article appeared on Medscape.com.

MILAN, ITALY — Pregnant women with heightened amygdala activity have a reduced capacity to regulate emotions and report more symptoms of depression than those with lower activity in this brain region, a new imaging study suggested.

If validated, these findings could pave the way for identifying women at higher risk for postpartum depression, said lead researcher Franziska Weinmar, MSc, from the University of Tübingen in Germany.

The study was presented at the 37th European College of Neuropsychopharmacology Congress.
 

Differences in Brain Activity

During pregnancy and the peripartum period, rising hormone levels create a “psychoneuroendocrinological window of vulnerability” for mental health in which 80% of women can develop transitory “baby blues,” and about one in seven develop more serious postpartum depression, Ms. Weinmar told this news organization.

The study included 47 women — 15 pregnant women and 32 nonpregnant controls. The nonpregnant women had normal menstrual cycles; 16 were in the early follicular phase with low estradiol levels (231.7 pmol/L), and 16 had high estradiol levels (516.6 pmol/L) after administration of estradiol.

To examine brain activity, participants were asked to view negative emotional images while undergoing functional MRI. They were then asked to use cognitive reappraisal to regulate their emotional response to the images.

The findings showed that both pregnant and nonpregnant women were equally successful at emotional regulation, but this process involved different brain activity in pregnant vs their nonpregnant counterpart.

All women had increased left middle frontal gyrus activity when regulating their emotions, but there was a difference in the amygdala between the pregnancy group and controls, Ms. Weinmar noted.

This suggests that pregnant women may have to exert more neural effort in emotional regulation, she said. “And pregnant women with higher amygdala activity were less able to regulate their emotions successfully compared to those with less amygdala activity.”

Linear regression analyses were performed to assess the relation of brain activity during down-regulation, regulation success, and self-reported depression scores, and this showed that higher amygdala activity was also associated with higher depression scores.

“We need to be cautious in interpreting this,” said Ms. Weinmar. “This is a small sample, and we are the first to undertake this work.”

Nonetheless, she said that if the findings are confirmed by larger studies, pregnant women could be assessed “in the waiting room” using existing questionnaires that evaluate emotional regulation.

If a woman has difficulties with emotion regulation, “there are adaptive strategies, like cognitive reappraisal that a counseling psychotherapist can help with,” said Ms. Weinmar.

“I could also imagine group sessions, for example, or online courses,” she said, adding that obstetricians could also be trained to identify these women.

Commenting on the findings in a press release, Susana Carmona, PhD, from Gregorio Marañón Hospital in Madrid, Spain, said research like this is crucial for gaining insight into one of the most intense physiological processes a human can undergo: pregnancy. It’s remarkable how much remains unknown.

“Recently, the FDA [Food and Drug Administration] approved the first treatment for postpartum depression. However, we still have a long way to go in characterizing what happens in the brain during pregnancy, identifying biomarkers that can indicate the risk of developing perinatal mental disorders, and designing strategies to prevent mother and infant suffering during the delicate and critical peripartum period,” Dr. Carmona added.

The study was supported by the Center for Integrative Neuroscience in Tübingen, Germany, and the International Research Training Group “Women’s Mental Health Across the Reproductive Years” (IRTG 2804). Ms. Weinmar and Dr. Carmona reported no relevant disclosures.

A version of this article appeared on Medscape.com.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

THE DIAGNOSIS: Dengue Hemorrhagic Fever

The retiform purpura observed in our patient was suggestive of a vasculitic, thrombotic, or embolic etiology. Dengue IgM serologic testing performed based on her extensive travel history and recent return from a dengue-endemic area was positive, indicating acute infection. A clinical diagnosis of dengue hemorrhagic fever (DHF) was made based on the hemorrhagic appearance of the lesion. Histopathology revealed leukocytoclastic vasculitis (Figure). Anti–double-stranded DNA, antideoxyribonuclease, C3 and C4, CH50 (total hemolytic complement), antineutrophil cytoplasmic antibodies, HIV, and hepatitis B virus tests were normal. Direct immunofluorescence was negative.

Dengue virus is a single-stranded RNA virus transmitted by Aedes aegypti and Aedes albopictus mosquitoes and is one of the most prevalent arthropod-borne viruses affecting humans today.^1,2 Infection with the dengue virus generally is seen in travelers visiting tropical regions of Africa, Mexico, South America, South and Central Asia, Southeast Asia, and the Caribbean.¹ The Table shows the global distribution of dengue serotypes from 2000 to 2014.^3,4 There are 4 serotypes of the dengue virus: DENV-1 to DENV-4. Infection with 1 strain elicits longlasting immunity to that strain, but subsequent infection with another strain can result in severe DHF due to antibody cross-reaction.¹

Dengue virus infection ranges from mildly symptomatic to a spectrum of increasingly severe conditions that comprise dengue fever (DF) and DHF, as well as dengue shock syndrome and brain stem hemorrhage, which may be fatal.^2,5 Dengue fever manifests as severe myalgia, fever, headache (usually retro-orbital), arthralgia, erythema, and rubelliform exanthema.⁶ The frequency of skin eruptions in patients with DF varies with the virus strain and outbreaks.⁷ The lesions initially develop with the onset of fever and manifest as flushing or erythematous mottling of the face, neck, and chest areas.^1,7 The morbilliform eruption develops 2 to 6 days after the onset of the fever, beginning on the trunk and spreading to the face and extremities.^1,7 The rash may become confluent with characteristic sparing of small round areas of normal skin described as white islands in a sea of red.² Verrucous papules on the ears also have been described and may resemble those seen in Cowden syndrome. In patients with prior infection with a different strain of the virus, hemorrhagic lesions may develop, including characteristic retiform purpura, a positive tourniquet test, and the appearance of petechiae on the lower legs. Pruritus and desquamation, especially on the palms and soles, may follow the termination of the eruption.⁷

The differential diagnosis of DF includes measles, rubella, enteroviruses, and influenza. Chikungunya and West Nile viruses in Asia and Africa and the O’nyong-nyong virus in Africa are also arboviruses that cause a clinical picture similar to DF but not DHF. Other diagnostic considerations include phases of scarlet fever, typhoid, malaria, leptospirosis, hepatitis A, and trypanosomal and rickettsial diseases.⁷ The differential diagnosis of DHF includes antineutrophil cytoplasmic antibody–associated vasculitis, rheumatoid vasculitis, and bacterial septic vasculitis.

Acute clinical diagnosis of DF can be challenging because of the nonspecific symptoms that can be seen in almost every infectious disease. Clinical presentation assessment should be confirmed with laboratory testing.⁶ Dengue virus infection usually is confirmed by the identification of viral genomic RNA, antigens, or the antibodies it elicits. Enzyme-linked immunosorbent assay–based serologic tests are cost-effective and easy to perform.⁵ IgM antibodies usually show cross-reactivity with platelets, but the antibody levels are not positively correlated with the severity of DF.⁸ Primary infection with the dengue virus is characterized by the elevation of specific IgM levels that usually occurs 3 to 5 days after symptom onset and persists during the postfebrile stage (up to 30 to 60 days). In secondary infections, the IgM levels usually rise more slowly and reach a lower level than in primary infections.⁹ For both primary and secondary infections, testing IgM levels after the febrile stage may be helpful with the laboratory diagnosis.

Currently, there is no antiviral drug available for dengue. Treatment of dengue infection is symptomatic and supportive.²

Dengue hemorrhagic fever is indicated by a rising hematocrit (≥20%) and a falling platelet count (>100,000/mm³) accompanying clinical signs of hemorrhage. Treatment includes intravenous fluid replacement and careful clinical monitoring of hematocrit levels, platelet count, vitals, urine output, and other signs of shock.⁵ For patients with a history of dengue infection, travel to areas with other serotypes is not recommended.

If any travel to a high-risk area is planned, countryspecific travel recommendations and warnings should be reviewed from the Centers for Disease Control and Prevention’s website (https://wwwnc.cdc.gov/travel/notices/level1/dengue-global). Use of an Environmental Protection Agency–registered insect repellent to avoid mosquito bites and acetaminophen for managing symptoms is advised. During travel, staying in places with window and door screens and using a bed net during sleep are suggested. Long-sleeved shirts and long pants also are preferred. Travelers should see a health care provider if they have symptoms of dengue.¹⁰

African tick bite fever (ATBF) is caused by Rickettsia africae transmitted by Amblyomma ticks. Skin findings in ATBF include erythematous, firm, tender papules with central eschars consistent with the feeding patterns of ticks.¹¹ Histopathology of ATBF usually includes fibrinoid necrosis of vessels in the dermis with a perivascular inflammatory infiltrate and coagulation necrosis of the surrounding dermis consistent with eschar formation.¹² The lack of an eschar weighs against this diagnosis.

African trypanosomiasis (also known as sleeping sickness) is caused by protozoa transmitted by the tsetse fly. A chancrelike, circumscribed, rubbery, indurated red or violaceous nodule measuring 2 to 5 cm in diameter often develops as the earliest cutaneous sign of the disease.¹³ Nonspecific histopathologic findings, such as infiltration of lymphocytes and macrophages and proliferation of endothelial cells and fibroblasts, may be observed.¹⁴ Extravascular parasites have been noted in skin biopsies.¹⁵ In later stages, skin lesions called trypanids may be observed as macular, papular, annular, targetoid, purpuric, and erythematous lesions, and histopathologic findings consistent with vasculitis also may be seen.¹³

Chikungunya virus infection is an acute-onset, mosquito-borne viral disease. Skin manifestations may start with nonspecific, generalized, morbilliform, maculopapular rashes coinciding with fever, which also may be seen initially with DHF. Skin hyperpigmentation, mostly centrofacial and involving the nose (chik sign); purpuric and ecchymotic lesions over the trunk and flexors of limbs in adults, often surmounted by subepidermal bullae and lesions resembling toxic epidermal necrolysis; and nonhealing ulcers in the genital and groin areas are common skin manifestations of chikungunya infection.¹⁶ Intraepithelial splitting with acantholysis and perivascular lymphohistiocytic infiltration may be observed in the histopathology of blistering lesions, which are not consistent with DHF.¹⁷

Zika virus infection is caused by an arbovirus within the Flaviviridae family, which also includes the dengue virus. Initial mucocutaneous findings of the Zika virus include nonspecific diffuse maculopapular eruptions. The eruption generally spares the palms and soles; however, various manifestations including involvement of the palms and soles have been reported.¹⁸ The morbilliform eruption begins on the face and extends to the trunk and extremities. Mild hemorrhagic manifestations, including petechiae and bleeding gums, may be observed. Distinguishing between dengue and Zika virus infection relies on the severity of symptoms and laboratory tests, including polymerase chain reaction or IgM antibody testing.¹⁹ The other conditions listed do not produce hemorrhagic fever.

Percutaneous endoscopic gastrostomy (PEG) was first introduced in the early 1980s by surgeons Michael Gauderer and Jeffrey Ponsky as a less-invasive alternative to surgical gastrostomy via open laparotomy. The concept was born after the pair observed that the light from an endoscope in an infant undergoing endoscopy caused the abdominal wall to glow in the darkened operating room.

In fact, PEG was among the first procedures that defined minimally invasive surgery, a concept that has now revolutionized the surgical field. Since that time, PEG has evolved as a preferred method for patients needing long-term nutritional support for various indications. By 2001, approximately 216,000 PEGs were placed annually in the United States. While the volume of PEG procedures has declined in recent years at some institutions as practice patterns have shifted toward interventional radiology–placed gastrostomy tubes, evaluation of patients for PEG insertion, removal, or management of PEG complications remains a core area of gastroenterology practice.

University of Michigan

Among the most important roles of the gastroenterologist in considering potential PEG candidates is to determine whether an appropriate indication exists, a decision that requires a detailed understanding of a patient’s overall clinical condition, goals of care, values, and preferences. This month’s Ethics Corner column provides important expert insights on navigating the complex ethical and clinical issues relating to PEG placement, a common GI consultation that deserves thoughtful consideration and demands effective communication among members of the multidisciplinary team and with patients.

Also in our October issue, we highlight a recently published large multicohort study from Gastroenterology elucidating clinical, serologic, and genetic factors associated with extraintestinal manifestations in IBD. We also review key updates to colonoscopy quality indicators, including modifications to existing indicators such as ADR and the addition of two new “priority indicators” — rate of inadequate bowel prep and sessile serrated lesion detection rate.

In this month’s Member Spotlight, Dr. Stephanie Pointer of Digestive & Liver Health Specialists in Nashville, Tennessee, shares the many ways in which she has given back to her community through music and mentoring while leading a thriving GI practice. We hope you enjoy this, and all the coverage included in our October issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

Percutaneous endoscopic gastrostomy (PEG) was first introduced in the early 1980s by surgeons Michael Gauderer and Jeffrey Ponsky as a less-invasive alternative to surgical gastrostomy via open laparotomy. The concept was born after the pair observed that the light from an endoscope in an infant undergoing endoscopy caused the abdominal wall to glow in the darkened operating room.

In fact, PEG was among the first procedures that defined minimally invasive surgery, a concept that has now revolutionized the surgical field. Since that time, PEG has evolved as a preferred method for patients needing long-term nutritional support for various indications. By 2001, approximately 216,000 PEGs were placed annually in the United States. While the volume of PEG procedures has declined in recent years at some institutions as practice patterns have shifted toward interventional radiology–placed gastrostomy tubes, evaluation of patients for PEG insertion, removal, or management of PEG complications remains a core area of gastroenterology practice.

University of Michigan

Among the most important roles of the gastroenterologist in considering potential PEG candidates is to determine whether an appropriate indication exists, a decision that requires a detailed understanding of a patient’s overall clinical condition, goals of care, values, and preferences. This month’s Ethics Corner column provides important expert insights on navigating the complex ethical and clinical issues relating to PEG placement, a common GI consultation that deserves thoughtful consideration and demands effective communication among members of the multidisciplinary team and with patients.

Also in our October issue, we highlight a recently published large multicohort study from Gastroenterology elucidating clinical, serologic, and genetic factors associated with extraintestinal manifestations in IBD. We also review key updates to colonoscopy quality indicators, including modifications to existing indicators such as ADR and the addition of two new “priority indicators” — rate of inadequate bowel prep and sessile serrated lesion detection rate.

In this month’s Member Spotlight, Dr. Stephanie Pointer of Digestive & Liver Health Specialists in Nashville, Tennessee, shares the many ways in which she has given back to her community through music and mentoring while leading a thriving GI practice. We hope you enjoy this, and all the coverage included in our October issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

Percutaneous endoscopic gastrostomy (PEG) was first introduced in the early 1980s by surgeons Michael Gauderer and Jeffrey Ponsky as a less-invasive alternative to surgical gastrostomy via open laparotomy. The concept was born after the pair observed that the light from an endoscope in an infant undergoing endoscopy caused the abdominal wall to glow in the darkened operating room.

In fact, PEG was among the first procedures that defined minimally invasive surgery, a concept that has now revolutionized the surgical field. Since that time, PEG has evolved as a preferred method for patients needing long-term nutritional support for various indications. By 2001, approximately 216,000 PEGs were placed annually in the United States. While the volume of PEG procedures has declined in recent years at some institutions as practice patterns have shifted toward interventional radiology–placed gastrostomy tubes, evaluation of patients for PEG insertion, removal, or management of PEG complications remains a core area of gastroenterology practice.

University of Michigan

Among the most important roles of the gastroenterologist in considering potential PEG candidates is to determine whether an appropriate indication exists, a decision that requires a detailed understanding of a patient’s overall clinical condition, goals of care, values, and preferences. This month’s Ethics Corner column provides important expert insights on navigating the complex ethical and clinical issues relating to PEG placement, a common GI consultation that deserves thoughtful consideration and demands effective communication among members of the multidisciplinary team and with patients.

Also in our October issue, we highlight a recently published large multicohort study from Gastroenterology elucidating clinical, serologic, and genetic factors associated with extraintestinal manifestations in IBD. We also review key updates to colonoscopy quality indicators, including modifications to existing indicators such as ADR and the addition of two new “priority indicators” — rate of inadequate bowel prep and sessile serrated lesion detection rate.

In this month’s Member Spotlight, Dr. Stephanie Pointer of Digestive & Liver Health Specialists in Nashville, Tennessee, shares the many ways in which she has given back to her community through music and mentoring while leading a thriving GI practice. We hope you enjoy this, and all the coverage included in our October issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

The global withdrawal of voxelotor (Oxbryta, Pfizer) has left clinicians who treat sickle cell disease (SCD) with the urgent task of reaching patients taking the medicine, while trying to understand why it was taken off the market.

The National Alliance of Sickle Cell Centers issued a statement urging patients not to stop voxelotor abruptly. Instead, they should work out plans with their physicians and medical teams for weaning plans.

“Don’t lose faith. This a step backward, but we will stay on the path to better outcomes for everyone,” said the alliance in a statement to patients and clinicians.

On September 25, Pfizer said it would withdraw all lots of voxelotor in all markets where it is approved. The New York–based drugmaker also said it was discontinuing all active voxelotor clinical trials and expanded access programs worldwide. The cause was data that suggested “an imbalance in vaso-occlusive crises and fatal events which require further assessment.”

Pfizer told this news organization in an email exchange that it is focused on analyzing the data and will share updates in the future about presenting or publishing on this issue.

The withdrawal came amid increased scrutiny of the drug by the European Medicines Agency (EMA). The EMA in July began a review of voxelotor after data from a clinical trial showed that a higher number of deaths occurred with the drug than with placebo and another trial showed the total number of deaths was higher than anticipated.

On September 26, the EMA’s human medicines committee recommended suspending the marketing authorization of voxelotor, citing new safety data that emerged during the review. The drug had received marketing authorization for the European Union in 2022, the agency said.

The US Food and Drug Administration (FDA), which first cleared voxelotor for sale in 2019, also said it has been conducting a safety review of the drug. The agency continues to examine post-marketing clinical trial data for voxelotor, the real-world registry studies, and data from the FDA Adverse Event Reporting System. At the conclusion of this review, the FDA will communicate any additional findings, if necessary, the agency said.

The FDA said it appeared that more deaths and a higher rate of vaso-occlusive crisis occurred in patients taking voxelotor vs placebo in post-marketing clinical trials.

“Pfizer also observed a higher rate of vaso-occlusive crisis in patients with sickle cell disease receiving Oxbryta in two real-world registry studies,” the FDA said. “Based on the totality of clinical data, Pfizer has determined the benefit of Oxbryta does not outweigh the risk.”
 

Gene Therapy, Tried-and-True Hydroxyurea (HU)

As a field, SCD has drawn more interest in recent years, with significant gains made lately in cutting-edge projects.

The FDA in December approved two gene-editing treatments for patients aged 12 years or older. These are considered “milestone treatments” for a debilitating and potentially life-threatening blood disorder that affects about 100,000 people in the United States. Exagamglogene autotemcel (Casgevy, Vertex Pharmaceuticals and CRISPR Therapeutics) is the first to use the gene-editing tool CRISPR. And lovotibeglogene autotemcel (Lyfgenia, bluebird bio) uses a different gene-editing tool called a lentiviral vector.

These advances have been covered widely by the news media but are not expected to be widely available, with the cost of these extensive treatments estimated around $2-$3 million per patient.

“Gene therapy is amazing in that it can offer a cure, but it’s very expensive and not all patients are suitable for it. Some have so much existing organ damage that it’s not an option for them,” said John Wood, MD, PhD, director of cardiovascular MRI at Children’s Hospital Los Angeles, Los Angeles, who does research on SCD.

“So it really is a great treatment for a very few people,” he said in an interview.

The mainstay of treatment for SCD remains a drug that Lydia Pecker, MD, a pediatric hematologist at Johns Hopkins University in Baltimore, describes as the “first, oldest, and best”: HU.

The FDA approved this in 1998 for use in SCD. It reduces the frequency of painful crises and acute chest syndrome and other complications of SCD that otherwise could be serious or even lethal, Pecker said.

“Older doctors can tell you that what they experienced with sickle cell disease in the hospitals has been completely transformed because of the high uptake of the drug,” she said, adding that it made a “profound” change. “We just don’t have data for any other agent that’s quite like that.”

Voxelotor had been a good second drug to add for some patients, in addition to HU and blood transfusions, Dr. Pecker noted. It was a first-line drug for those for whom transfusion and HU were not options, which constitutes a relatively small number of patients, she said.

“So we have, in the last 5 years, felt more hopeful because we had something else to offer,” she said.

Alexis A. Thompson, MD, MPH, chief of the Division of Hematology at Children’s Hospital of Philadelphia in Pennsylvania, said in an interview that her organization also had patients who appeared to benefit from voxelotor, some of whom had been participants in clinical trials.

Dr. Thompson, who has been a top researcher involved in the study of gene therapy, urged the need for companies to keep seeking to expand the options for people with SCD, even after the setback with voxelotor.

“I hope that there’s an appreciation for the need for continued investment in this very serious condition, for which there are insufficient options for treatments,” Dr. Thompson said. “So ongoing investment is really needed if we expect to make progress.”

Dr. Pecker disclosed ties with Novartis, Afimmune, the American Society of Hematology, and the National Institutes of Health. Thompson reported relationships with bluebird bio, Beam, Editas, Novartis, and Novo Nordisk.
 

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Demand for new weight loss drugs has surged over the past few years. 

Led by the antiobesity drugs semaglutide (Wegovy) and tirzepatide (Zepbound), these popular medications — more commonly known as glucagon-like peptide 1 (GLP-1) agonists — have become game changers for shedding excess pounds.

Aside from obesity indications, both drugs have been approved to treat type 2 diabetes under different brand names and have a growing list of other potential benefits, such as reducing inflammation and depression. 

These antiobesity drugs could even have a place in cancer care.

While there’s limited data to support the use of GLP-1 agonists for weight loss in cancer, some oncologists have begun carefully integrating the antiobesity agents into care and studying their effects in this patient population.

The reason: Research suggests that obesity can reduce the effectiveness of cancer therapies, especially in patients with breast cancer, and can increase the risk for treatment-related side effects. 

The idea is that managing patients’ weight will improve their cancer outcomes, explained Lajos Pusztai, MD, PhD, a breast cancer specialist and professor of medicine at Yale School of Medicine in New Haven, Connecticut. 

Although Dr. Pusztai and his oncology peers at Yale don’t yet use GPL-1 agonists, Neil Iyengar, MD, and colleagues have begun doing so to help some patients with breast cancer manage their weight. Dr. Iyengar estimates that a few hundred — almost 40% — of his patients are on the antiobesity drugs.

“For a patient who has really tried to reduce their weight and who is in the obese range, that’s where I think the use of these medications can be considered,” said Dr. Iyengar, a breast cancer oncologist at Memorial Sloan Kettering Cancer Center in New York City. 

Why GLP-1s in Cancer?

GLP-1 is a hormone that the small intestine releases after eating. GLP-1 agonists work by mimicking GLP-1 to trigger the release of insulin and reduce the production of glucagon — two processes that help regulate blood sugar. 

These agents, such as Wegovy (or Ozempic when prescribed for diabetes), also slow gastric emptying and can make people feel fuller longer. 

Zebound (or Mounjaro for type 2 diabetes) is considered a dual GLP-1 and glucose-dependent insulinotropic polypeptide agonist, which may enhance its weight loss benefits.

In practice, however, these drugs can increase nausea and vomiting from chemotherapy, so Dr. Iyengar typically has patients use them afterwards, during maintenance treatment.

Oncologists don’t prescribe the drugs themselves but instead refer patients to endocrinologists or weight management centers that then write the prescriptions. Taking these drugs involves weekly subcutaneous injections patients can administer themselves.

Endocrinologist Emily Gallagher, MD, PhD, of Mount Sinai Hospital in New York City, estimates she has prescribed the antiobesity drugs to a few hundred patients with cancer and, like Dr. Iyengar, uses the drugs during maintenance treatment with hormone therapy for breast cancer. She also has used these agents in patients with prostate and endometrial cancers and has found the drugs can help counter steroid weight gain in multiple myeloma. 

But, to date, the evidence for using GPL-1 agonists in cancer remains limited and the practice has not yet become widespread.

Research largely comes down to a few small retrospective studies in patients with breast cancer receiving aromatase inhibitors. Although no safety issues have emerged so far, these initial reports suggest that the drugs lead to significantly less weight loss in patients with cancer compared to the general population. 

Dr. Iyengar led one recent study, presented at the 2024 annual meeting of the American Society of Clinical Oncology, in which he and his team assessed outcomes in 75 women with breast cancer who received a GLP-1 agonist. Almost 80% of patients had diabetes, and 60% received hormone therapy, most commonly an aromatase inhibitor. Patients’ median body mass index (BMI) at baseline was 34 kg/m² (range, 23-50 kg/m²).

From baseline, patients lost 6.2 kg, on average, or about 5% of their total body weight, 12 months after initiating GLP-1 therapy. 

In contrast, phase 3 trials show much higher mean weight loss — about two times — in patients without cancer. 

Another recent study also reported modest weight loss results in patients with breast cancer undergoing endocrine therapy. The researchers reported that, at 12 months, Wegovy led to 4.34% reduction in BMI, compared with a 14% change reported in the general population. Zebound, however, was associated with a 2.31% BMI increase overall — though some patients did experience a decrease — compared with a 15% reduction in the general population. 

“These findings indicate a substantially reduced weight loss efficacy in breast cancer patients on endocrine therapy compared to the general population,” the authors concluded.

It’s unclear why the drugs appear to not work as well in patients with cancer. It’s possible that hormone therapy or metabolic changes interfere with their effectiveness, given that some cancer therapies lead to weight gain. Steroids and hormone therapies, for instance, often increase appetite, and some treatments can slow patients’ metabolism or lead to fatigue, which can make it harder to exercise.

Patients with cancer may need a higher dose of GLP-1 agonists to achieve similar weight loss to the general population, Dr. Iyengar noted.

However, Dr. Gallagher said, in her own experience, she hasn’t found the drugs to be less effective in patients with cancer, especially the newer agents, like Wegovy and Zepbound. 

As for safety, Wegovy and Zepbound both carry a black box warning for thyroid C-cell tumors, including medullary thyroid carcinoma. (Recent research, however, has found that GLP-1 agonists do not increase thyroid cancer risk). 

These antiobesity agents are also contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients who have multiple endocrine neoplasia syndrome type 2, which is associated with medullary thyroid carcinoma.

Dr. Gallagher hasn’t seen any secondary tumors — thyroid or otherwise — in her patients with cancer, but she follows the labeling contraindications. Dr. Iyengar also noted that more recent and larger data sets have shown no impact on this risk, which may not actually exist, he said

Dr. Gallagher remains cautious about using GPL-1 agonists in patients who have had bariatric surgery because these agents can compound the slower gastric emptying and intestinal transit from surgery, potentially leading to gastrointestinal obstructions. 

Looking ahead, GPL-1 manufacturers are interested in adding cancer indications to the drug labeling. Both Dr. Iyengar and Dr. Gallagher said their institutions are in talks with companies to participate in large, multicenter, global phase 3 trials.

Dr. Iyengar welcomes the efforts, not only to test the effectiveness of GPL-1 agonists in oncology but also to “nail down” their safety in cancer. 

“I don’t think that there’s mechanistically anything that’s particularly worrisome,” and current observations suggest that these drugs are likely to be safe, Dr. Iyengar said. Even so, “GLP-1 agonists do a lot of things that we don’t fully understand yet.”

The bigger challenge, Dr. Iyengar noted, is that companies will have to show a sizable benefit to using these drugs in patients with cancer to get the Food and Drug Administration’s approval. And to move the needle on cancer-specific outcomes, these antiobesity drugs will need to demonstrate significant, durable weight loss in patients with cancer. 

But if these drugs can do that, “I think it’s going to be one of the biggest advances in medicine and oncology given the obesity and cancer epidemic,” Dr. Iyengar said. 

Dr. Iyengar has adviser and/or researcher ties with companies that make or are developing GPL-1 agonists, including AstraZeneca, Novartis, Gilead, and Pfizer. Dr. Gallagher is a consultant for Novartis, Flare Therapeutics, Reactive Biosciences, and Seagen.

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

Eliezer Masliah, MD, director of the neuroscience division at the National Institute on Aging (NIA), has been “relieved of his position” following an investigation by the National Institutes of Health (NIH) that turned up research misconduct, the NIH said in a statement.

The misconduct involved “falsification and/or fabrication involving reuse and relabel of figure panels representing different experimental results in two publications,” the NIH said.

The agency said it will notify the two journals of its findings so that appropriate action can be taken.

The NIH reportedly launched its probe into potential research misconduct in May 2023 after it received allegations from the Health and Human Service (HHS) Office of Research Integrity (ORI) that month.

The investigation phase began in December 2023 and concluded on September 15, 2024. The institute subsequently notified HHS ORI of its findings.

Dr. Masliah joined the NIH in the summer of 2016 as director of the Division of Neuroscience at the NIA and an NIH intramural researcher investigating synaptic damage in neurodegenerative disorders, publishing “numerous” papers, the NIH said.

Given the findings of their investigation, the NIH said, Dr. Masliah is no longer serving as director of NIA’s Division of Neuroscience.

NIA deputy director Amy Kelley, MD, is now acting director of NIA’s neuroscience division.

Consistent with NIH policies and procedures, any allegations involving Dr. Masliah’s NIH-supported extramural research prior to joining NIH would be referred to HHS ORI, the NIH said.

The NIH announcement came on the same day that Science magazine published an investigative piece suggesting that Dr. Masliah may have fabricated or falsified images or other information in far more than the two studies NIH cited.

According to the article, “scores” of Dr. Masliah’s lab studies conducted at the NIA and the University of California San Diego are “riddled with apparently falsified Western blots — images used to show the presence of proteins — and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.”

The article noted that a neuroscientist and forensic analysts who had previously worked with Science magazine produced a “300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers.”

They concluded that this “pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” the Science article stated.
 

A version of this article appeared on Medscape.com.

Eliezer Masliah, MD, director of the neuroscience division at the National Institute on Aging (NIA), has been “relieved of his position” following an investigation by the National Institutes of Health (NIH) that turned up research misconduct, the NIH said in a statement.

The misconduct involved “falsification and/or fabrication involving reuse and relabel of figure panels representing different experimental results in two publications,” the NIH said.

The agency said it will notify the two journals of its findings so that appropriate action can be taken.

The NIH reportedly launched its probe into potential research misconduct in May 2023 after it received allegations from the Health and Human Service (HHS) Office of Research Integrity (ORI) that month.

The investigation phase began in December 2023 and concluded on September 15, 2024. The institute subsequently notified HHS ORI of its findings.

Dr. Masliah joined the NIH in the summer of 2016 as director of the Division of Neuroscience at the NIA and an NIH intramural researcher investigating synaptic damage in neurodegenerative disorders, publishing “numerous” papers, the NIH said.

Given the findings of their investigation, the NIH said, Dr. Masliah is no longer serving as director of NIA’s Division of Neuroscience.

NIA deputy director Amy Kelley, MD, is now acting director of NIA’s neuroscience division.

Consistent with NIH policies and procedures, any allegations involving Dr. Masliah’s NIH-supported extramural research prior to joining NIH would be referred to HHS ORI, the NIH said.

The NIH announcement came on the same day that Science magazine published an investigative piece suggesting that Dr. Masliah may have fabricated or falsified images or other information in far more than the two studies NIH cited.

According to the article, “scores” of Dr. Masliah’s lab studies conducted at the NIA and the University of California San Diego are “riddled with apparently falsified Western blots — images used to show the presence of proteins — and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.”

The article noted that a neuroscientist and forensic analysts who had previously worked with Science magazine produced a “300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers.”

They concluded that this “pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” the Science article stated.
 

A version of this article appeared on Medscape.com.

Eliezer Masliah, MD, director of the neuroscience division at the National Institute on Aging (NIA), has been “relieved of his position” following an investigation by the National Institutes of Health (NIH) that turned up research misconduct, the NIH said in a statement.

The misconduct involved “falsification and/or fabrication involving reuse and relabel of figure panels representing different experimental results in two publications,” the NIH said.

The agency said it will notify the two journals of its findings so that appropriate action can be taken.

The NIH reportedly launched its probe into potential research misconduct in May 2023 after it received allegations from the Health and Human Service (HHS) Office of Research Integrity (ORI) that month.

The investigation phase began in December 2023 and concluded on September 15, 2024. The institute subsequently notified HHS ORI of its findings.

Dr. Masliah joined the NIH in the summer of 2016 as director of the Division of Neuroscience at the NIA and an NIH intramural researcher investigating synaptic damage in neurodegenerative disorders, publishing “numerous” papers, the NIH said.

Given the findings of their investigation, the NIH said, Dr. Masliah is no longer serving as director of NIA’s Division of Neuroscience.

NIA deputy director Amy Kelley, MD, is now acting director of NIA’s neuroscience division.

Consistent with NIH policies and procedures, any allegations involving Dr. Masliah’s NIH-supported extramural research prior to joining NIH would be referred to HHS ORI, the NIH said.

The NIH announcement came on the same day that Science magazine published an investigative piece suggesting that Dr. Masliah may have fabricated or falsified images or other information in far more than the two studies NIH cited.

According to the article, “scores” of Dr. Masliah’s lab studies conducted at the NIA and the University of California San Diego are “riddled with apparently falsified Western blots — images used to show the presence of proteins — and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.”

The article noted that a neuroscientist and forensic analysts who had previously worked with Science magazine produced a “300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers.”

They concluded that this “pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” the Science article stated.
 

A version of this article appeared on Medscape.com.

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer

EDITOR’S NOTE

This year, we again focus on rare neurological diseases that have new therapies that have been recently approved as well as conditions for which the treatment pipeline is robust. Let’s hope the work of many dedicated researchers adds to the list of rare neurological diseases for which treatment is available.

This year also marks a change of leadership at NORD, our publishing partner in this annual supplement. We here at Neurology Reviews salute the leadership and accomplishments of former NORD CEO Peter Saltonstall and also welcome incoming CEO Pamela Gavin, who has spent many years in NORD leadership roles and was essential in the planning, launch, and early years of this annual supplement. I can think of no one better than Pamela Gavin to continue NORD’s mission into the future.

And finally, a recap of accolades for this annual supplement. For the second year in a row, the Rare Neurological Disease Special Report has won an Azbee award in the category of annual supplement from the American Society of Business Publication Editors. The 2023 issue won a National Gold Award and a Regional Gold Award.

—Glenn Williams, VP, Group Editor, Neurology Reviews and MDedge Neurology

A NOTE FROM NORD

Hello, and Welcome! The National Organization for Rare Disorders (NORD) is pleased to partner with Neurology Reviews to bring you the 2024 edition of the Rare Neurological Disease Report. Through this collaboration, we share cutting-edge research and insights from leading medical experts, including specialists from the NORD Rare Disease Centers of Excellence network, about the latest advances in the treatment of rare neurological conditions.

As healthcare providers, you play a key role in catalyzing advancements and bringing new hope and possibilities to the rare disease community. Your efforts can contribute to shortening the diagnostic odyssey and improving day-to-day care for people living with rare disorders in crucial ways:

Identifying patients: Healthcare providers can recognize the possible signs of a rare disease and initiate further investigation or referral to specialists. Early detection is key as it can lead to a quicker, more accurate diagnosis, better management, and improved outcomes.

Educating other physicians: Many rare diseases are not well-known or understood by the general medical community. Healthcare providers can help bridge this knowledge gap by educating other physicians about rare conditions. They can raise awareness through clinical teaching, seminars, medical literature, or continuing medical education (CME) sessions focused on rare diseases. Raising awareness and providing up-to-date information about rare diseases bolsters diagnostic and treatment capabilities within the medical field.

Providing information to patients: Once a rare disease is identified, healthcare providers can offer valuable support to patients and their families. They can provide potential treatments and management strategies. They can also connect patients with support groups, support programs, educational resources, and specialists with expertise in specific rare conditions. Clear communication and guidance on support resources can positively impact patients’ well-being, empower them to make informed decisions, and help them navigate a complex rare condition.

This issue of the Rare Disease Neurological Special Report features articles by rare disease medical experts on specific diseases with updates on clinical management. Topics include the diagnosis and management of Duchenne muscular dystrophy, the promise of disease-modifying therapies for Huntington’s disease, patient choices and cultural changes around myasthenia gravis, advances in neuromyelitis optica, and untangling chronic inflammatory demyelinating polyneuropathy. In addition, two online-only articles offer timely insights from key opinion leaders on the pros and cons of genetic testing and what clinicians need to know about newborn screening.

You will also find information about the NORD Rare Diseases and Orphan Products Breakthrough Summit. This annual event convenes thought leaders from patient advocacy organizations, industry, academia, medical and research institutions, and government to discuss critical topics facing the rare disease community. 

NORD is deeply appreciative of healthcare professionals like you, who despite long hours and demanding workloads, remain committed to staying up to date on the latest medical advances for the benefit of their patients. Your dedication and hard work make a significant difference to the patients and families we serve, and your commitment does not go unnoticed. Thank you for all that you do.

—Pamela Gavin, NORD Chief Executive Officer