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Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

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

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

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

Childhood cancers represent a diverse group of neoplasms, and thanks to advances in treatment, survival rates have improved significantly. Today, more than 80%-85% of children diagnosed with cancer in developed countries survive into adulthood.

This increase in survival has brought new challenges, however. Compared with the general population, childhood cancer survivors (CCS) are at a notably higher risk for early mortality, developing secondary cancers, and experiencing various long-term clinical and psychosocial issues stemming from their disease or its treatment.

Long-term follow-up care for CCS is a complex and evolving field. Despite ongoing efforts to establish global and national guidelines, current evidence indicates that the care and management of these patients remain suboptimal.

Sexual dysfunction is a common and significant late effect among CCS. The disruptions caused by cancer and its treatment can interfere with normal physiological and psychological development, leading to issues with sexual function. This aspect of health is critical as it influences not just physical well-being but also psychosocial, developmental, and emotional health.
 

Characteristics and Mechanisms

Sexual functioning encompasses the physiological and psychological aspects of sexual behavior, including desire, arousal, orgasm, sexual pleasure, and overall satisfaction.

As CCS reach adolescence or adulthood, they often face sexual and reproductive issues, particularly as they enter romantic relationships.

Sexual functioning is a complex process that relies on the interaction of various factors, including physiological health, psychosexual development, romantic relationships, body image, and desire.

Despite its importance, the impact of childhood cancer on sexual function is often overlooked, even though cancer and its treatments can have lifelong effects. 
 

Sexual Function in CCS

A recent review aimed to summarize the existing research on sexual function among CCS, highlighting assessment tools, key stages of psychosexual development, common sexual problems, and the prevalence of sexual dysfunction.

The review study included 22 studies published between 2000 and 2022, comprising two qualitative, six cohort, and 14 cross-sectional studies.

Most CCS reached all key stages of psychosexual development at an average age of 29.8 years. Although some milestones were achieved later than is typical, many survivors felt they reached these stages at the appropriate time. Sexual initiation was less common among those who had undergone intensive neurotoxic treatments, such as those diagnosed with brain tumors or leukemia in childhood.

In a cross-sectional study of CCS aged 17-39 years, about one third had never engaged in sexual intercourse, 41.4% reported never experiencing sexual attraction, 44.8% were dissatisfied with their sex lives, and many rarely felt sexually attractive to others. Another study found that common issues among CCS included a lack of interest in sex (30%), difficulty enjoying sex (24%), and difficulty becoming aroused (23%). However, comparing and analyzing these problems was challenging due to the lack of standardized assessment criteria.

The prevalence of sexual dysfunction among CCS ranged from 12.3% to 46.5%. For males, the prevalence ranged from 12.3% to 54.0%, while for females, it ranged from 19.9% to 57.0%.
 

Factors Influencing Sexual Function

The review identified the following four categories of factors influencing sexual function in CCS: Demographic, treatment-related, psychological, and physiological.

Demographic factors: Gender, age, education level, relationship status, income level, and race all play roles in sexual function.

Female survivors reported more severe sexual dysfunction and poorer sexual health than did male survivors. Age at cancer diagnosis, age at evaluation, and the time since diagnosis were closely linked to sexual experiences. Patients diagnosed with cancer during childhood tended to report better sexual function than those diagnosed during adolescence.

Treatment-related factors: The type of cancer and intensity of treatment, along with surgical history, were significant factors. Surgeries involving the spinal cord or sympathetic nerves, as well as a history of prostate or pelvic surgery, were strongly associated with erectile dysfunction in men. In women, pelvic surgeries and treatments to the pelvic area were commonly linked to sexual dysfunction.

The association between treatment intensity and sexual function was noted across several studies, although the results were not always consistent. For example, testicular radiation above 10 Gy was positively correlated with sexual dysfunction. Women who underwent more intensive treatments were more likely to report issues in multiple areas of sexual function, while men in this group were less likely to have children.

Among female CCS, certain types of cancer, such as germ cell tumors, renal tumors, and leukemia, present a higher risk for sexual dysfunction. Women who had CNS tumors in childhood frequently reported problems like difficulty in sexual arousal, low sexual satisfaction, infrequent sexual activity, and fewer sexual partners, compared with survivors of other cancers. Survivors of acute lymphoblastic leukemia and those who underwent hematopoietic stem cell transplantation (HSCT) also showed varying degrees of impaired sexual function, compared with the general population. The HSCT group showed significant testicular damage, including reduced testicular volumes, low testosterone levels, and low sperm counts.

Psychological factors: These factors, such as emotional distress, play a significant role in sexual dysfunction among CCS. Symptoms like anxiety, nervousness during sexual activity, and depression are commonly reported by those with sexual dysfunction. The connection between body image and sexual function is complex. Many CCS with sexual dysfunction express concern about how others, particularly their partners, perceived their altered body image due to cancer and its treatment.

Physiological factors: In male CCS, low serum testosterone levels and low lean muscle mass are linked to an increased risk for sexual dysfunction. Treatments involving alkylating agents or testicular radiation, and surgery or radiotherapy targeting the genitourinary organs or the hypothalamic-pituitary region, can lead to various physiological and endocrine disorders, contributing to sexual dysfunction. Despite these risks, there is a lack of research evaluating sexual function through the lens of the hypothalamic-pituitary-gonadal axis and neuroendocrine pathways.
 

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

This transcript has been edited for clarity.

I heard recently about a fascinating, important development in artificial intelligence (AI). All kinds of things are happening in AI. Clearly, it’s being used in the background to trace and keep track of medical information inside hospitals.

There are AI bots out there that are starting to talk to patients about, say, mental health issues. Plenty of people are using AI to get information about their medical condition, seeing it supplement search engines, and on and on AI goes. 

It has entered into a space where I think patients may raise questions about whether they should use it or seek opinions from doctors and nurses, particularly those involved with seriously ill people. That space is grieving, and what might be called “death bots.”

Here’s what’s going on. There’s a gentleman I read about online, who was dying of end-stage colon cancer. His wife and he were talking, knowing his death was coming, about what it would be like after his death. She said she would really miss being able to ask him questions about a variety of topics that he was expert at and that he knew very well. 

He thought about it and decided, well, maybe he could record his voice and then use AI to search information that he would record and have available, which could really address questions that his wife might put to “him” once he was gone.

It turns out that a company was formed shortly thereafter, which is now offering the service both in the US and Europe, and in fact, I think perhaps even worldwide, basically saying we’ll record a dying person’s voice. We will help people grieve by allowing people to interact with the AI version of the departed when they’re gone. 

It will be able to, if you will, search not just recorded information but anything they might have online — diaries, things they may have written, earlier videos, and information from earlier parts of their life — to generate plausible answers to questions that might be put to the artificial version of the deceased.

Obviously, this would allow not only spouses but grandchildren and people in future generations to have some way to interact with an ancestor who’s gone. It may allow people to feel comfort when they miss a loved one, to hear their voice, and not just in a prerecorded way but creatively interacting with them.

On the other hand, there are clearly many ethical issues about creating an artificial version of yourself. One obvious issue is how accurate this AI version of you will be if the death bot can create information that sounds like you, but really isn’t what you would have said, despite the effort to glean it from recordings and past information about you. Is it all right if people wander from the truth in trying to interact with someone who’s died? 

There are other ways to leave memories behind. You certainly can record messages so that you can control the content. Many people video themselves and so on. There are obviously people who would say that they have a diary or have written information they can leave behind. 

Is there a place in terms of accuracy for a kind of artificial version of ourselves to go on forever? Another interesting issue is who controls that. Can you add to it after your death? Can information be shared about you with third parties who don’t sign up for the service? Maybe the police take an interest in how you died. You can imagine many scenarios where questions might come up about wanting to access these data that the artificial agent is providing. 

Some people might say that it’s just not the way to grieve. Maybe the best way to grieve is to accept death and not try to interact with a constructed version of yourself once you’ve passed. That isn’t really accepting death. It’s a form, perhaps, of denial of death, and maybe that isn’t going to be good for the mental health of survivors who really have not come to terms with the fact that someone has passed on.

I’m not against these death bots or AI versions of trying to leave a legacy. There are all kinds of legacies that people might want to leave. While perhaps not 100% accurate, I can see how this technology has a use. 

I do think one has to go in with their eyes open. We need consent before anything like this is really purchased by or sold to surviving people. They really have to understand it may not be an accurate version of what the deceased might have said in response to questions, conversations, or interactions. 

I think we need to know who controls the information, who can erase it, and who can say, “I’m done with it, and I don’t want my husband’s AI to go on anymore.”

All that said, it’s an interesting development in a world in which I think those who are very ill might start to plan to leave a legacy that is more than just a diary or a video message. It becomes a kind of ongoing, artificial, interactive version of themselves that may provide some people with comfort.

Dr. Caplan, director of the Division of Medical Ethics at New York University Langone Medical Center, New York City, reported conflicts of interest with Johnson & Johnson and Medscape.

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

This transcript has been edited for clarity.

I heard recently about a fascinating, important development in artificial intelligence (AI). All kinds of things are happening in AI. Clearly, it’s being used in the background to trace and keep track of medical information inside hospitals.

There are AI bots out there that are starting to talk to patients about, say, mental health issues. Plenty of people are using AI to get information about their medical condition, seeing it supplement search engines, and on and on AI goes. 

It has entered into a space where I think patients may raise questions about whether they should use it or seek opinions from doctors and nurses, particularly those involved with seriously ill people. That space is grieving, and what might be called “death bots.”

Here’s what’s going on. There’s a gentleman I read about online, who was dying of end-stage colon cancer. His wife and he were talking, knowing his death was coming, about what it would be like after his death. She said she would really miss being able to ask him questions about a variety of topics that he was expert at and that he knew very well. 

He thought about it and decided, well, maybe he could record his voice and then use AI to search information that he would record and have available, which could really address questions that his wife might put to “him” once he was gone.

It turns out that a company was formed shortly thereafter, which is now offering the service both in the US and Europe, and in fact, I think perhaps even worldwide, basically saying we’ll record a dying person’s voice. We will help people grieve by allowing people to interact with the AI version of the departed when they’re gone. 

It will be able to, if you will, search not just recorded information but anything they might have online — diaries, things they may have written, earlier videos, and information from earlier parts of their life — to generate plausible answers to questions that might be put to the artificial version of the deceased.

Obviously, this would allow not only spouses but grandchildren and people in future generations to have some way to interact with an ancestor who’s gone. It may allow people to feel comfort when they miss a loved one, to hear their voice, and not just in a prerecorded way but creatively interacting with them.

On the other hand, there are clearly many ethical issues about creating an artificial version of yourself. One obvious issue is how accurate this AI version of you will be if the death bot can create information that sounds like you, but really isn’t what you would have said, despite the effort to glean it from recordings and past information about you. Is it all right if people wander from the truth in trying to interact with someone who’s died? 

There are other ways to leave memories behind. You certainly can record messages so that you can control the content. Many people video themselves and so on. There are obviously people who would say that they have a diary or have written information they can leave behind. 

Is there a place in terms of accuracy for a kind of artificial version of ourselves to go on forever? Another interesting issue is who controls that. Can you add to it after your death? Can information be shared about you with third parties who don’t sign up for the service? Maybe the police take an interest in how you died. You can imagine many scenarios where questions might come up about wanting to access these data that the artificial agent is providing. 

Some people might say that it’s just not the way to grieve. Maybe the best way to grieve is to accept death and not try to interact with a constructed version of yourself once you’ve passed. That isn’t really accepting death. It’s a form, perhaps, of denial of death, and maybe that isn’t going to be good for the mental health of survivors who really have not come to terms with the fact that someone has passed on.

I’m not against these death bots or AI versions of trying to leave a legacy. There are all kinds of legacies that people might want to leave. While perhaps not 100% accurate, I can see how this technology has a use. 

I do think one has to go in with their eyes open. We need consent before anything like this is really purchased by or sold to surviving people. They really have to understand it may not be an accurate version of what the deceased might have said in response to questions, conversations, or interactions. 

I think we need to know who controls the information, who can erase it, and who can say, “I’m done with it, and I don’t want my husband’s AI to go on anymore.”

All that said, it’s an interesting development in a world in which I think those who are very ill might start to plan to leave a legacy that is more than just a diary or a video message. It becomes a kind of ongoing, artificial, interactive version of themselves that may provide some people with comfort.

Dr. Caplan, director of the Division of Medical Ethics at New York University Langone Medical Center, New York City, reported conflicts of interest with Johnson & Johnson and Medscape.

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

This transcript has been edited for clarity.

I heard recently about a fascinating, important development in artificial intelligence (AI). All kinds of things are happening in AI. Clearly, it’s being used in the background to trace and keep track of medical information inside hospitals.

There are AI bots out there that are starting to talk to patients about, say, mental health issues. Plenty of people are using AI to get information about their medical condition, seeing it supplement search engines, and on and on AI goes. 

It has entered into a space where I think patients may raise questions about whether they should use it or seek opinions from doctors and nurses, particularly those involved with seriously ill people. That space is grieving, and what might be called “death bots.”

Here’s what’s going on. There’s a gentleman I read about online, who was dying of end-stage colon cancer. His wife and he were talking, knowing his death was coming, about what it would be like after his death. She said she would really miss being able to ask him questions about a variety of topics that he was expert at and that he knew very well. 

He thought about it and decided, well, maybe he could record his voice and then use AI to search information that he would record and have available, which could really address questions that his wife might put to “him” once he was gone.

It turns out that a company was formed shortly thereafter, which is now offering the service both in the US and Europe, and in fact, I think perhaps even worldwide, basically saying we’ll record a dying person’s voice. We will help people grieve by allowing people to interact with the AI version of the departed when they’re gone. 

It will be able to, if you will, search not just recorded information but anything they might have online — diaries, things they may have written, earlier videos, and information from earlier parts of their life — to generate plausible answers to questions that might be put to the artificial version of the deceased.

Obviously, this would allow not only spouses but grandchildren and people in future generations to have some way to interact with an ancestor who’s gone. It may allow people to feel comfort when they miss a loved one, to hear their voice, and not just in a prerecorded way but creatively interacting with them.

On the other hand, there are clearly many ethical issues about creating an artificial version of yourself. One obvious issue is how accurate this AI version of you will be if the death bot can create information that sounds like you, but really isn’t what you would have said, despite the effort to glean it from recordings and past information about you. Is it all right if people wander from the truth in trying to interact with someone who’s died? 

There are other ways to leave memories behind. You certainly can record messages so that you can control the content. Many people video themselves and so on. There are obviously people who would say that they have a diary or have written information they can leave behind. 

Is there a place in terms of accuracy for a kind of artificial version of ourselves to go on forever? Another interesting issue is who controls that. Can you add to it after your death? Can information be shared about you with third parties who don’t sign up for the service? Maybe the police take an interest in how you died. You can imagine many scenarios where questions might come up about wanting to access these data that the artificial agent is providing. 

Some people might say that it’s just not the way to grieve. Maybe the best way to grieve is to accept death and not try to interact with a constructed version of yourself once you’ve passed. That isn’t really accepting death. It’s a form, perhaps, of denial of death, and maybe that isn’t going to be good for the mental health of survivors who really have not come to terms with the fact that someone has passed on.

I’m not against these death bots or AI versions of trying to leave a legacy. There are all kinds of legacies that people might want to leave. While perhaps not 100% accurate, I can see how this technology has a use. 

I do think one has to go in with their eyes open. We need consent before anything like this is really purchased by or sold to surviving people. They really have to understand it may not be an accurate version of what the deceased might have said in response to questions, conversations, or interactions. 

I think we need to know who controls the information, who can erase it, and who can say, “I’m done with it, and I don’t want my husband’s AI to go on anymore.”

All that said, it’s an interesting development in a world in which I think those who are very ill might start to plan to leave a legacy that is more than just a diary or a video message. It becomes a kind of ongoing, artificial, interactive version of themselves that may provide some people with comfort.

Dr. Caplan, director of the Division of Medical Ethics at New York University Langone Medical Center, New York City, reported conflicts of interest with Johnson & Johnson and Medscape.

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

A new “best practices” guide released by the Alliance for Pharmacy Compounding (APC) aims to educate compounding pharmacists and reassure prescribers about the ethical, legal, and practical considerations that must be addressed to ensure quality standards and protect patients’ health.

Endocrinologists have expressed skepticism about the quality of compounded drugs, particularly the popular glucagon-like peptide 1 (GLP-1) semaglutide. The Food and Drug Administration (FDA) recently issued an alert linking hospitalizations to overdoses of compounded semaglutide.

“This document goes beyond today’s media-grabbing shortages,” APC Board Chair-Elect Gina Besteman, RPh, of Belmar Pharma Solutions told this news organization. “We developed these best practices to apply to all shortage drug compounding, and especially in this moment when so many are compounding GLP-1s. These serve as a reminder about what compliance and care look like.”

Prescribers determine whether a patient needs a compounded medication, not pharmacists, Ms. Besteman noted. “A patient-specific prescription order must be authorized for a compounded medication to be dispensed. Prescribers should ensure pharmacies they work with regularly check the FDA Drug Shortage List, as compounding of ‘essential copies’ of FDA-approved drugs is only allowed when a drug is listed as ‘currently in shortage.’ ”
 

Framework for Compounding

“With fake and illegal online stores popping up, it’s critical for legitimate, state-licensed compounding pharmacies to maintain the profession’s high standards,” the APC said in a media communication.

Highlights of its best practices, which are directed toward 503A state-licensed compounding pharmacies, include the following, among others:

• Pharmacies should check the FDA drug shortage list prior to preparing a copy of an FDA-approved drug and maintain documentation to demonstrate to regulators that the drug was in shortage at the time it was compounded.
• Pharmacies may only source active pharmaceutical ingredients (APIs) from state-licensed wholesalers who purchase from FDA-registered manufacturers or order directly from FDA-registered manufacturers.
• Verify from the wholesaler that the manufacturer is registered with the FDA and the API meets all the requirements of section 503A, and that both hold the appropriate permits or licenses in their home state and the shipped to state.
• Adhere to USP Chapter <797> testing requirements for sterility, endotoxin, stability, particulate, antimicrobial effectiveness, and container closure integrity studies.
• Counseling must be offered to the patient or the patient’s agent/caregiver. Providing written information that assists in the understanding of how to properly use the compounded medication is advised.
• Instructions should be written in a way that a layperson can understand (especially directions including dosage titrations and conversions between milligrams and milliliters or units).
• Like all medications, compounded drugs can only be prescribed in the presence of a valid patient-practitioner relationship and can only be dispensed by a pharmacy after receipt of a valid patient-specific prescription order.
• When marketing, never make claims of safety or efficacy of the compounded product.
• Advertising that patients will/may save money using compounded medications, compared with manufactured products is not allowed.

“Compounding FDA-approved drugs during shortages is nothing new — pharmacies have been doing it well before GLP-1s came on the scene, and they’ll continue long after this current shortage ends,” Ms. Besteman said. “Prescribers should be aware of APC’s guidelines because they provide a framework for ethically and legally compounding medications during drug shortages.

“To paraphrase The Police,” she concluded, “every move you make, every step you take, they’ll be watching you. Make sure they see those best practices in action.”
 

‘Reduces the Risks’

Commenting on the best practices guidance, Ivania Rizo, MD, director of Obesity Medicine and Diabetes and clinical colead at Boston Medical Center’s Health Equity Accelerator in Massachusetts, said: “These best practices will hopefully make a difference in the quality of compounded drugs.”

“The emphasis on rigorous testing of APIs and adherence to USP standards is particularly important for maintaining drug quality,” she noted. “This structured approach reduces the risk of variability and ensures that compounded drugs meet high-quality standards, thus enhancing their reliability.”

“Knowing that compounding pharmacies are adhering to rigorous standards for sourcing, testing, and compounding can at least reassure clinicians that specific steps are being taken for the safety and efficacy of these medications,” she said. “The transparency in documenting compliance with FDA guidelines and maintaining high-quality control measures can enhance trust among healthcare providers.”

Although clinicians are likely to have more confidence in compounded drugs when these best practices are followed, she said, “overall, we all hope that the shortages of medications such as tirzepatide are resolved promptly, allowing patients to access FDA-approved drugs without the need for compounding.”

“While the implementation of best practices for compounding during shortages is a positive and necessary step, our ultimate goal remains to address and resolve these shortages in the near future,” she concluded.

Dr. Rizo declared no competing interests.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

Since the first Food and Drug Administration approval of a Janus kinase (JAK) inhibitor in 2011, the number of these medications available — and their treatment indications — have continued to grow. Prescribing physicians are familiar with the benefits and risks for these drugs, including higher risk for cardiac events and malignancy; however, one adverse effect may be overlooked, especially by specialties outside of dermatology: acne. Though less serious than some other side effects, JAK inhibitor–associated acne — JAKne, for short — can be a concern for patients.

“Your physical appearance and how you present yourself to the world is an important part of your self-confidence and living life on your own terms,” said Arash Mostaghimi, MD, the director of inpatient dermatology at Brigham and Women’s Hospital in Boston, Massachusetts. “I think letting people know about [JAKne] and then addressing it when it occurs should be a normal part of managing these medications.”
 

What Is JAKne?

JAKne generally looks like other kinds of acne, explained Janelle Nassim, MD, director of laser and cosmetic dermatology at the Indiana University School of Medicine, Indianapolis. “It can affect the same areas that typical acne affects, including the face, chest, back, neck, and upper shoulders.”

Though it appears like typical forms of acne, it is not clear what drives these skin eruptions in patients taking JAK inhibitors.

courtesy Brigham and Women&#039;s Hospital

“We don’t understand the underlying pathophysiology,” Dr. Mostaghimi said. “It looks like acne, but we don’t know if the exact underlying inflammatory process is the same or if it’s different.”

In a 2023 systematic review of clinical studies, Dr. Mostaghimi and colleagues found that patients on any JAK inhibitor were nearly four times more likely to experience acne than patients who received placebo, but risk varied between medications. Patients taking JAK inhibitors for skin conditions had higher risk for acne than those given the medications for other indications. However, Dr. Mostaghimi thinks this finding is the result of selection bias.

Participants may not mention side effects like acne in trials for rheumatologic or gastrointestinal conditions, he said, unlike in trials for skin conditions. “Clinically, I’ve seen it in patients across every indication.”

Patients with a history of acne seem to be more likely to develop this side effect, though formal studies looking into risk factors are lacking. In Dr. Mostaghimi’s own clinical experience, JAKne is also more common in younger patients, but it can happen to anyone. “I’ve seen 70-year-olds develop acne — patients who’ve never had an issue their whole life — when they’re taking a JAK inhibitor.”

This issue also appears to be more common earlier in treatment, he added, and may improve over time as a patient continues with the medication.
 

How Do You Treat It?

“I think in other specialties, you will often feel awkward addressing skin conditions or pointing out acne,” Dr. Mostaghimi said. The most important steps are being aware of this potential side effect, and if you see it practice, to bring it up.

“Say: I’m noticing there’s some changes in your skin. Some patients on JAK inhibitors develop more acne. Have you noticed this? And if so, is this bothering you?”

Generally, JAKne is mild to moderate, explained Dr. Nassim, and if non-dermatologists are comfortable, they can prescribe a first-line topical regimen for patients. Dr. Mostaghimi recommends prescribing a clindamycin 1% lotion or gel. In addition, patients can use a benzoyl peroxide wash (4% or 10%) combined with a gentle retinoid, such as adapalene. (Both of these treatments are now available over the counter.)

courtesy Harvard Medical School

In patients with scalp or hairline involvement, he often prescribes a ketoconazole 2% shampoo, which patients can use to wash their scalp, face, chest, and back in the shower.

If they aren’t responding to these initial treatments, then refer to a dermatologist for further assessment.

“Ultimately, referring to a dermatologist is the best course of action,” Dr. Nassim said. “I have had patients on JAK inhibitors who improved with topical acne treatments, and some that required more aggressive treatment with oral medications.”

Dr. Mostaghimi reported consulting fees from AbbVie, Concert Pharmaceuticals, Pfizer, and 3Derm Systems; research funding from Incyte, Aclaris Therapeutics, Eli Lilly, and Concert Pharmaceuticals; personal fees from Equillium, ASLAN Pharmaceuticals, ACOM, and Boehringer Ingelheim; and advisory board fees from Fig.1 Beauty, Eli Lilly, Pfizer, and Hims & Hers Health. Dr. Nassim had no relevant disclosures.

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

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has declined to approve linvoseltamab (Regeneron), a bispecific antibody being evaluated to treat relapsed/refractory multiple myeloma after progression on at least three previous therapies.

On August 20, Regeneron announced that it had received a complete response letter from the FDA regarding its Biologics License Application for linvoseltamab, citing issues at a third-party manufacturer.

More specifically, Regeneron said in a company press release that the FDA issued the complete response letter based on findings from “a preapproval inspection at a third-party fill/finish manufacturer for another company’s product candidate.”

The third-party manufacturer told Regeneron it believes that the issues have been resolved, Regeneron said, and that facility is now awaiting a follow-up FDA inspection in the “coming months.”

Regeneron noted that this “anticipated outcome” from the FDA preapproval inspection had been disclosed previously during a company earnings call on August 1.

On that call, Regeneron had discussed the FDA’s concerns about the third-party manufacturer and anticipated that “any potential FDA approval for linvoseltamab is likely to be delayed beyond the August 22 PDUFA date.”

Regeneron had initially filed a Biologics License Application for its bispecific antibody in 2023, based on findings from the phase 1/2 single arm LINKER-MM1 trial. 

In the latest published trial findings, investigators reported that, at a median follow-up of about 14 months, 71% of the 117 patients receiving 200 mg of linvoseltamab achieved an overall response, with 50% achieving a complete response. The probability of survival at 12 months was 75.3%.

This would have been the first approval for linvoseltamab, which would have joined two agents already on the US market for relapsed/refractory multiple myeloma: teclistamab (Tecvayli, Janssen) and elranatamab (Elrexfio, Pfizer).

Pricing information for linvoseltamab is not yet available, but its competitors teclistamab and elranatamab are reported to cost around $40,000 per month.
 

A version of this article appeared on Medscape.com.

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

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

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

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

Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office. 

The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.

In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
 

Meeting the Criteria

The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:

• The disease that the test screens for must have a presymptomatic form.
• The screening test must be able to identify this presymptomatic disease.
• Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
• The screening test is feasible, and the benefits outweigh potential risks.

“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.

The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
 

Inappropriate Endpoints?

Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.

Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.

“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”

Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.
 

An NHS Study

Arguments for different endpoints apparently resonated with the United Kingdom’s National Health Service (NHS). Three years ago, they initiated the Galleri study, a large randomized controlled trial to assess the effectiveness of Grail’s cancer test. The primary endpoint was not cancer-specific mortality, but the incidence of stage III or IV cancer.

The results are expected in 2026. But recruitment was stopped after 140,000 participants were enrolled. The NHS reported that the initial results were not convincing enough to continue the trial. Exact numbers were not disclosed.

The Galleri study deviates from the standard randomized controlled trial design for cancer screening procedures not only in terms of the primary endpoint, but also in blinding. The only participants who were unblinded and informed of their test results are those in the intervention group with a positive cancer test.
 

False Security

This trial design encourages participants to undergo blood tests once per year. But according to Dr. Robbins, it prevents the exploration of the phenomenon of “false security,” which is a potential drawback of the new cancer tests.

“Women with a negative mammogram can reasonably assume that they probably do not have breast cancer. But individuals with a negative cancer blood test could mistakenly believe they cannot have any cancer at all. As a result, they may not undergo standard early detection screenings or seek medical help early enough for potential cancer symptoms,” said Dr. Robbins.

To assess the actual risk-benefit ratio of the Galleri test, participants must receive their test results, she said. “Under real-world conditions, benefits and risks can come from positive and negative results.” 
 

Upcoming Trial

More illuminating results may come from a large trial planned by the National Cancer Institute in the United States. Several new cancer tests will be evaluated for their ability to reduce cancer-specific mortality. A pilot phase will start later in 2024. “This study may be the only one with sufficient statistical power to determine whether an approach based on these cancer tests can reduce cancer-specific mortality,” said Dr. Robbins.

For the new blood tests for multiple cancers, it is crucial that health authorities “set a high bar for a benefit,” she said. This, according to her, also means that they must show an effect on cancer-specific mortality before being introduced. “This evidence must come from studies in which commercial interests do not influence the design, execution, data management, or data analysis.”

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

WASHINGTON, DC — Cutaneous immune-related adverse events (cirAEs) in oncology patients receiving immune checkpoint inhibitors (ICIs) should be treated in as targeted a fashion as possible and with judicious usage and dosing of prednisone when deemed necessary, Blair Allais, MD, said during a session on supportive oncodermatology at the ElderDerm conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.

“It’s important when you see these patients to be as specific as possible” based on morphology and histopathology, and to treat the rashes in a similar way as in the non-ICI setting,” said Dr. Allais, a dermato-oncologist at the Inova Schar Cancer Institute, Fairfax, Virginia.

cirAEs are the most frequently reported and most visible adverse effects of checkpoint inhibition — a treatment that has emerged as a standard therapy for many malignancies since the first ICI was approved in 2011 for metastatic melanoma.

And contrary to what the phenomenon of immunosenescence might suggest, older patients are no less prone to cirAEs than younger patients. “You’d think you’d have fewer rashes and side effects as you age, but that’s not true,” said Dr. Allais, who completed a fellowship in cutaneous oncology after her dermatology residency.

A 2021 multicenter international cohort study of over 900 patients aged ≥ 80 years treated with single-agent ICIs for cancer did not find any significant differences in the development of immune-related adverse events among those younger than 85, those aged 85-89 years, and those 90 and older. Neither did the ELDERS study in the United Kingdom; this prospective observational study found similar rates of high-grade and low-grade immune toxicity in its two cohorts of patients ≥ 70 and < 70 years of age.

At the meeting, Dr. Allais, who coauthored a 2023 review of cirAEs from ICIs, reviewed recent developments and provided the following advice:
 

New diagnostic criteria: “Really exciting” news for more precise diagnosis and optimal therapy of cirAEs, Dr. Allais said, is a position paper published in the Journal for ImmunoTherapy of Cancer that offers consensus-based diagnostic criteria for the 10 most common types of dermatologic immune-related adverse events and an overall diagnostic framework. “Luckily, through the work of a Delphi consensus group, we can now have [more diagnostic specificity],” which is important for both clinical care and research, she said.

Most cirAEs have typically been reported nonspecifically as “rash,” but diagnosing a rash subtype is “critical in tailoring appropriate therapy that it is both effective and the least detrimental to the oncology treatment plan for patients with cancer,” the group’s coauthors wrote.

The 10 core diagnoses include psoriasis, eczematous dermatitis, vitiligo, Grover disease, eruptive atypical squamous proliferation, and bullous pemphigoid. Outside of the core diagnoses are other nonspecific presentations that require evaluation to arrive at a diagnosis, if possible, or to reveal data that can allow for targeted therapy and severity grading, the group explains in its paper.

“To prednisone or not to prednisone”: The development of cirAEs is associated with reduced mortality and improved cancer outcomes, making the use of immunosuppressants such as corticosteroids a therapeutic dilemma. “Patients who get these rashes usually do better with respect to their cancer, so the concern has been, if we affect how they respond to their immunotherapy, we may minimize that improvement in mortality,” said Dr. Allais, also assistant professor at the University of Virginia, Charlottesville, and clinical assistant professor of dermatology at George Washington University.

A widely discussed study published in 2015 reported on 254 patients with melanoma who developed an immune-related adverse event during treatment with ipilimumab — approximately one third of whom required systemic corticosteroids — and concluded that systemic corticosteroids did not affect overall survival or time to (cancer) treatment failure. This study from Memorial Sloan Kettering Cancer Center, New York City, “was the first large study looking at this question,” she said, and the subsequent message for several years in conferences and the literature was that steroids do not affect the efficacy of checkpoint inhibitors.

“But the study was not without limitations,” Dr. Allais said, “because the patients who got prednisone were mainly those with higher-grade toxicities,” while those not treated with corticosteroids had either no toxicities or low-grade toxicities. “If higher-grade toxicities were associated with better (antitumor) response, the steroids may have just [blunted] that benefit.”

The current totality of data available in the literature suggests that corticosteroids may indeed have an impact on the efficacy of ICI therapy. “Subsequent studies have come out in the community that have shown that we should probably think twice about giving prednisone to some patients, particularly within the first 50 days of ICI treatment, and that we should be mindful of the dose,” Dr. Allais said.

The takeaways from these studies — all published in the past few years — are to use prednisone early and liberally for life-threatening toxicity, to use it at the lowest dose and for the shortest course when there is not an appropriate alternative, to avoid it for diagnoses that are not treated with prednisone outside the ICI setting, and to “have a plan” for a steroid-sparing agent to use after prednisone, she said.

Dr. Allais recommends heightened consideration during the first 50 days of ICI treatment based on a multicenter retrospective study that found a significant association between use of high-dose glucocorticoids (≥ 60 mg prednisone equivalent once a day) within 8 weeks of anti–programmed cell death protein 1 (PD-1) monotherapy initiation and poorer progression-free and overall survival. The study covered a cohort of 947 patients with advanced melanoma treated with anti–PD-1 monotherapy between 2009 and 2019, 54% of whom developed immune-related adverse events.

This study and other recent studies addressing the association between steroids and survival outcomes in patients with immune-related adverse events during ICI therapy are described in Dr. Allais’ 2023 review of cirAEs from ICIs.

Approach to morbilliform eruptions: This rash is “super common” in patients on ICIs, occurring generally within 2-3 weeks of starting treatment. “It tends to be self-limited and can recur with future infusions,” Dr. Allais said.

Systemic steroids should be reserved for severe or refractory eruptions. “Usually, I treat the patients with topical steroids, and I manage their expectations (that the rash may recur with subsequent infusions), but I closely follow them up” within 2-3 weeks, she said. It’s important to rule out a severe cutaneous adverse drug eruption, of course, and to start high-dose systemic steroids immediately if necessary. “Antibiotics are a big culprit” and often can be discontinued.

Soak and smear: “I’m obsessed” with this technique of a 20-minute soak in plain water followed by application of steroid ointment, said Dr. Allais, referring to a small study published in 2005 that reported a complete response after 2 weeks in 60% of patients with psoriasis, atopic dermatitis, and other inflammatory skin conditions (none had cancer), who had failed prior systemic therapy. All patients had at least a 75% response.

The method offers a way to “avoid the systemic immunosuppression we’d get with prednisone,” she said. One just needs to make sure the older patient can get in and out of their tub safely.

ICI-induced bullous pemphigoid (BP): BP occurs more frequently in the ICI setting, compared with the general population, with a median time to development of 8.5 months after ICI initiation. It is associated in this setting with improved tumor response, but “many oncologists stop anticancer treatment because of this diagnosis,” she said.

In the supportive oncodermatology space, however, ICI-induced BP exemplifies the value of tailored treatment regimens, she said. A small multi-institutional retrospective cohort study published in 2023 identified 35 cases of ICI-BP among 5636 ICI-treated patients and found that 8 out of 11 patients who received biologic therapy (rituximab, omalizumab, or dupilumab) had a complete response to ICI-BP without flares following subsequent ICI cycles. And while statistical significance was not reached, the study showed that no cancer-related outcomes were worsened.

“If you see someone with ICI-induced BP and they have a lot of involvement, you could start them on steroids and get that steroid-sparing agent initiated for approval. ... And if IgE is elevated, you might reach for omalizumab,” said Dr. Allais, noting that her favored treatment overall is dupilumab.

Risk factors for the development of ICI-induced BP include age > 70, skin cancer, and having an initial response to ICI on first imaging, the latter of which “I find fascinating ... because imaging occurs within the first 12 weeks of treatment, but we don’t see BP popping up until 8.5 months into treatment,” she noted. “So maybe there’s a baseline risk factor that could predispose them.”

Caution with antibiotics: “I try to avoid antibiotics in the ICI setting,” Dr. Allais said, in deference to the “ever-important microbiome.” Studies have demonstrated that the microbiomes of responders to ICI treatment are different from those of nonresponders, she said.

And a “fascinating” study of patients with melanoma undergoing ICI therapy showed not only a higher abundance of Ruminococcaceae bacteria in responders vs nonresponders but a significant impact of dietary fiber. High dietary fiber was associated with significantly improved overall survival in the patients on ICI, with the most pronounced benefit in patients with good fiber intake and no probiotic use. “Even wilder, their T cells changed,” she said. “They had a high expression of genes related to T-cell activation ... so more tumor-infiltrating lymphocytes.”

A retrospective study of 568 patients with stages III and IV melanoma treated with ICI showed that those exposed to antibiotics prior to ICI had significantly worse overall survival than those not exposed to antibiotics. “Think before you give them,” Dr. Allais said. “And try to tell your older patients to eat beans and greens.”

Dr. Allais reported having no relevant disclosures.

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

WASHINGTON, DC — Cutaneous immune-related adverse events (cirAEs) in oncology patients receiving immune checkpoint inhibitors (ICIs) should be treated in as targeted a fashion as possible and with judicious usage and dosing of prednisone when deemed necessary, Blair Allais, MD, said during a session on supportive oncodermatology at the ElderDerm conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.

“It’s important when you see these patients to be as specific as possible” based on morphology and histopathology, and to treat the rashes in a similar way as in the non-ICI setting,” said Dr. Allais, a dermato-oncologist at the Inova Schar Cancer Institute, Fairfax, Virginia.

cirAEs are the most frequently reported and most visible adverse effects of checkpoint inhibition — a treatment that has emerged as a standard therapy for many malignancies since the first ICI was approved in 2011 for metastatic melanoma.

And contrary to what the phenomenon of immunosenescence might suggest, older patients are no less prone to cirAEs than younger patients. “You’d think you’d have fewer rashes and side effects as you age, but that’s not true,” said Dr. Allais, who completed a fellowship in cutaneous oncology after her dermatology residency.

A 2021 multicenter international cohort study of over 900 patients aged ≥ 80 years treated with single-agent ICIs for cancer did not find any significant differences in the development of immune-related adverse events among those younger than 85, those aged 85-89 years, and those 90 and older. Neither did the ELDERS study in the United Kingdom; this prospective observational study found similar rates of high-grade and low-grade immune toxicity in its two cohorts of patients ≥ 70 and < 70 years of age.

At the meeting, Dr. Allais, who coauthored a 2023 review of cirAEs from ICIs, reviewed recent developments and provided the following advice:
 

New diagnostic criteria: “Really exciting” news for more precise diagnosis and optimal therapy of cirAEs, Dr. Allais said, is a position paper published in the Journal for ImmunoTherapy of Cancer that offers consensus-based diagnostic criteria for the 10 most common types of dermatologic immune-related adverse events and an overall diagnostic framework. “Luckily, through the work of a Delphi consensus group, we can now have [more diagnostic specificity],” which is important for both clinical care and research, she said.

Most cirAEs have typically been reported nonspecifically as “rash,” but diagnosing a rash subtype is “critical in tailoring appropriate therapy that it is both effective and the least detrimental to the oncology treatment plan for patients with cancer,” the group’s coauthors wrote.

The 10 core diagnoses include psoriasis, eczematous dermatitis, vitiligo, Grover disease, eruptive atypical squamous proliferation, and bullous pemphigoid. Outside of the core diagnoses are other nonspecific presentations that require evaluation to arrive at a diagnosis, if possible, or to reveal data that can allow for targeted therapy and severity grading, the group explains in its paper.

“To prednisone or not to prednisone”: The development of cirAEs is associated with reduced mortality and improved cancer outcomes, making the use of immunosuppressants such as corticosteroids a therapeutic dilemma. “Patients who get these rashes usually do better with respect to their cancer, so the concern has been, if we affect how they respond to their immunotherapy, we may minimize that improvement in mortality,” said Dr. Allais, also assistant professor at the University of Virginia, Charlottesville, and clinical assistant professor of dermatology at George Washington University.

A widely discussed study published in 2015 reported on 254 patients with melanoma who developed an immune-related adverse event during treatment with ipilimumab — approximately one third of whom required systemic corticosteroids — and concluded that systemic corticosteroids did not affect overall survival or time to (cancer) treatment failure. This study from Memorial Sloan Kettering Cancer Center, New York City, “was the first large study looking at this question,” she said, and the subsequent message for several years in conferences and the literature was that steroids do not affect the efficacy of checkpoint inhibitors.

“But the study was not without limitations,” Dr. Allais said, “because the patients who got prednisone were mainly those with higher-grade toxicities,” while those not treated with corticosteroids had either no toxicities or low-grade toxicities. “If higher-grade toxicities were associated with better (antitumor) response, the steroids may have just [blunted] that benefit.”

The current totality of data available in the literature suggests that corticosteroids may indeed have an impact on the efficacy of ICI therapy. “Subsequent studies have come out in the community that have shown that we should probably think twice about giving prednisone to some patients, particularly within the first 50 days of ICI treatment, and that we should be mindful of the dose,” Dr. Allais said.

The takeaways from these studies — all published in the past few years — are to use prednisone early and liberally for life-threatening toxicity, to use it at the lowest dose and for the shortest course when there is not an appropriate alternative, to avoid it for diagnoses that are not treated with prednisone outside the ICI setting, and to “have a plan” for a steroid-sparing agent to use after prednisone, she said.

Dr. Allais recommends heightened consideration during the first 50 days of ICI treatment based on a multicenter retrospective study that found a significant association between use of high-dose glucocorticoids (≥ 60 mg prednisone equivalent once a day) within 8 weeks of anti–programmed cell death protein 1 (PD-1) monotherapy initiation and poorer progression-free and overall survival. The study covered a cohort of 947 patients with advanced melanoma treated with anti–PD-1 monotherapy between 2009 and 2019, 54% of whom developed immune-related adverse events.

This study and other recent studies addressing the association between steroids and survival outcomes in patients with immune-related adverse events during ICI therapy are described in Dr. Allais’ 2023 review of cirAEs from ICIs.

Approach to morbilliform eruptions: This rash is “super common” in patients on ICIs, occurring generally within 2-3 weeks of starting treatment. “It tends to be self-limited and can recur with future infusions,” Dr. Allais said.

Systemic steroids should be reserved for severe or refractory eruptions. “Usually, I treat the patients with topical steroids, and I manage their expectations (that the rash may recur with subsequent infusions), but I closely follow them up” within 2-3 weeks, she said. It’s important to rule out a severe cutaneous adverse drug eruption, of course, and to start high-dose systemic steroids immediately if necessary. “Antibiotics are a big culprit” and often can be discontinued.

Soak and smear: “I’m obsessed” with this technique of a 20-minute soak in plain water followed by application of steroid ointment, said Dr. Allais, referring to a small study published in 2005 that reported a complete response after 2 weeks in 60% of patients with psoriasis, atopic dermatitis, and other inflammatory skin conditions (none had cancer), who had failed prior systemic therapy. All patients had at least a 75% response.

The method offers a way to “avoid the systemic immunosuppression we’d get with prednisone,” she said. One just needs to make sure the older patient can get in and out of their tub safely.

ICI-induced bullous pemphigoid (BP): BP occurs more frequently in the ICI setting, compared with the general population, with a median time to development of 8.5 months after ICI initiation. It is associated in this setting with improved tumor response, but “many oncologists stop anticancer treatment because of this diagnosis,” she said.

In the supportive oncodermatology space, however, ICI-induced BP exemplifies the value of tailored treatment regimens, she said. A small multi-institutional retrospective cohort study published in 2023 identified 35 cases of ICI-BP among 5636 ICI-treated patients and found that 8 out of 11 patients who received biologic therapy (rituximab, omalizumab, or dupilumab) had a complete response to ICI-BP without flares following subsequent ICI cycles. And while statistical significance was not reached, the study showed that no cancer-related outcomes were worsened.

“If you see someone with ICI-induced BP and they have a lot of involvement, you could start them on steroids and get that steroid-sparing agent initiated for approval. ... And if IgE is elevated, you might reach for omalizumab,” said Dr. Allais, noting that her favored treatment overall is dupilumab.

Risk factors for the development of ICI-induced BP include age > 70, skin cancer, and having an initial response to ICI on first imaging, the latter of which “I find fascinating ... because imaging occurs within the first 12 weeks of treatment, but we don’t see BP popping up until 8.5 months into treatment,” she noted. “So maybe there’s a baseline risk factor that could predispose them.”

Caution with antibiotics: “I try to avoid antibiotics in the ICI setting,” Dr. Allais said, in deference to the “ever-important microbiome.” Studies have demonstrated that the microbiomes of responders to ICI treatment are different from those of nonresponders, she said.

And a “fascinating” study of patients with melanoma undergoing ICI therapy showed not only a higher abundance of Ruminococcaceae bacteria in responders vs nonresponders but a significant impact of dietary fiber. High dietary fiber was associated with significantly improved overall survival in the patients on ICI, with the most pronounced benefit in patients with good fiber intake and no probiotic use. “Even wilder, their T cells changed,” she said. “They had a high expression of genes related to T-cell activation ... so more tumor-infiltrating lymphocytes.”

A retrospective study of 568 patients with stages III and IV melanoma treated with ICI showed that those exposed to antibiotics prior to ICI had significantly worse overall survival than those not exposed to antibiotics. “Think before you give them,” Dr. Allais said. “And try to tell your older patients to eat beans and greens.”

Dr. Allais reported having no relevant disclosures.

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

WASHINGTON, DC — Cutaneous immune-related adverse events (cirAEs) in oncology patients receiving immune checkpoint inhibitors (ICIs) should be treated in as targeted a fashion as possible and with judicious usage and dosing of prednisone when deemed necessary, Blair Allais, MD, said during a session on supportive oncodermatology at the ElderDerm conference on dermatology in the older patient hosted by the George Washington University School of Medicine and Health Sciences, Washington, DC.

“It’s important when you see these patients to be as specific as possible” based on morphology and histopathology, and to treat the rashes in a similar way as in the non-ICI setting,” said Dr. Allais, a dermato-oncologist at the Inova Schar Cancer Institute, Fairfax, Virginia.

cirAEs are the most frequently reported and most visible adverse effects of checkpoint inhibition — a treatment that has emerged as a standard therapy for many malignancies since the first ICI was approved in 2011 for metastatic melanoma.

And contrary to what the phenomenon of immunosenescence might suggest, older patients are no less prone to cirAEs than younger patients. “You’d think you’d have fewer rashes and side effects as you age, but that’s not true,” said Dr. Allais, who completed a fellowship in cutaneous oncology after her dermatology residency.

A 2021 multicenter international cohort study of over 900 patients aged ≥ 80 years treated with single-agent ICIs for cancer did not find any significant differences in the development of immune-related adverse events among those younger than 85, those aged 85-89 years, and those 90 and older. Neither did the ELDERS study in the United Kingdom; this prospective observational study found similar rates of high-grade and low-grade immune toxicity in its two cohorts of patients ≥ 70 and < 70 years of age.

At the meeting, Dr. Allais, who coauthored a 2023 review of cirAEs from ICIs, reviewed recent developments and provided the following advice:
 

New diagnostic criteria: “Really exciting” news for more precise diagnosis and optimal therapy of cirAEs, Dr. Allais said, is a position paper published in the Journal for ImmunoTherapy of Cancer that offers consensus-based diagnostic criteria for the 10 most common types of dermatologic immune-related adverse events and an overall diagnostic framework. “Luckily, through the work of a Delphi consensus group, we can now have [more diagnostic specificity],” which is important for both clinical care and research, she said.

Most cirAEs have typically been reported nonspecifically as “rash,” but diagnosing a rash subtype is “critical in tailoring appropriate therapy that it is both effective and the least detrimental to the oncology treatment plan for patients with cancer,” the group’s coauthors wrote.

The 10 core diagnoses include psoriasis, eczematous dermatitis, vitiligo, Grover disease, eruptive atypical squamous proliferation, and bullous pemphigoid. Outside of the core diagnoses are other nonspecific presentations that require evaluation to arrive at a diagnosis, if possible, or to reveal data that can allow for targeted therapy and severity grading, the group explains in its paper.

“To prednisone or not to prednisone”: The development of cirAEs is associated with reduced mortality and improved cancer outcomes, making the use of immunosuppressants such as corticosteroids a therapeutic dilemma. “Patients who get these rashes usually do better with respect to their cancer, so the concern has been, if we affect how they respond to their immunotherapy, we may minimize that improvement in mortality,” said Dr. Allais, also assistant professor at the University of Virginia, Charlottesville, and clinical assistant professor of dermatology at George Washington University.

A widely discussed study published in 2015 reported on 254 patients with melanoma who developed an immune-related adverse event during treatment with ipilimumab — approximately one third of whom required systemic corticosteroids — and concluded that systemic corticosteroids did not affect overall survival or time to (cancer) treatment failure. This study from Memorial Sloan Kettering Cancer Center, New York City, “was the first large study looking at this question,” she said, and the subsequent message for several years in conferences and the literature was that steroids do not affect the efficacy of checkpoint inhibitors.

“But the study was not without limitations,” Dr. Allais said, “because the patients who got prednisone were mainly those with higher-grade toxicities,” while those not treated with corticosteroids had either no toxicities or low-grade toxicities. “If higher-grade toxicities were associated with better (antitumor) response, the steroids may have just [blunted] that benefit.”

The current totality of data available in the literature suggests that corticosteroids may indeed have an impact on the efficacy of ICI therapy. “Subsequent studies have come out in the community that have shown that we should probably think twice about giving prednisone to some patients, particularly within the first 50 days of ICI treatment, and that we should be mindful of the dose,” Dr. Allais said.

The takeaways from these studies — all published in the past few years — are to use prednisone early and liberally for life-threatening toxicity, to use it at the lowest dose and for the shortest course when there is not an appropriate alternative, to avoid it for diagnoses that are not treated with prednisone outside the ICI setting, and to “have a plan” for a steroid-sparing agent to use after prednisone, she said.

Dr. Allais recommends heightened consideration during the first 50 days of ICI treatment based on a multicenter retrospective study that found a significant association between use of high-dose glucocorticoids (≥ 60 mg prednisone equivalent once a day) within 8 weeks of anti–programmed cell death protein 1 (PD-1) monotherapy initiation and poorer progression-free and overall survival. The study covered a cohort of 947 patients with advanced melanoma treated with anti–PD-1 monotherapy between 2009 and 2019, 54% of whom developed immune-related adverse events.

This study and other recent studies addressing the association between steroids and survival outcomes in patients with immune-related adverse events during ICI therapy are described in Dr. Allais’ 2023 review of cirAEs from ICIs.

Approach to morbilliform eruptions: This rash is “super common” in patients on ICIs, occurring generally within 2-3 weeks of starting treatment. “It tends to be self-limited and can recur with future infusions,” Dr. Allais said.

Systemic steroids should be reserved for severe or refractory eruptions. “Usually, I treat the patients with topical steroids, and I manage their expectations (that the rash may recur with subsequent infusions), but I closely follow them up” within 2-3 weeks, she said. It’s important to rule out a severe cutaneous adverse drug eruption, of course, and to start high-dose systemic steroids immediately if necessary. “Antibiotics are a big culprit” and often can be discontinued.

Soak and smear: “I’m obsessed” with this technique of a 20-minute soak in plain water followed by application of steroid ointment, said Dr. Allais, referring to a small study published in 2005 that reported a complete response after 2 weeks in 60% of patients with psoriasis, atopic dermatitis, and other inflammatory skin conditions (none had cancer), who had failed prior systemic therapy. All patients had at least a 75% response.

The method offers a way to “avoid the systemic immunosuppression we’d get with prednisone,” she said. One just needs to make sure the older patient can get in and out of their tub safely.

ICI-induced bullous pemphigoid (BP): BP occurs more frequently in the ICI setting, compared with the general population, with a median time to development of 8.5 months after ICI initiation. It is associated in this setting with improved tumor response, but “many oncologists stop anticancer treatment because of this diagnosis,” she said.

In the supportive oncodermatology space, however, ICI-induced BP exemplifies the value of tailored treatment regimens, she said. A small multi-institutional retrospective cohort study published in 2023 identified 35 cases of ICI-BP among 5636 ICI-treated patients and found that 8 out of 11 patients who received biologic therapy (rituximab, omalizumab, or dupilumab) had a complete response to ICI-BP without flares following subsequent ICI cycles. And while statistical significance was not reached, the study showed that no cancer-related outcomes were worsened.

“If you see someone with ICI-induced BP and they have a lot of involvement, you could start them on steroids and get that steroid-sparing agent initiated for approval. ... And if IgE is elevated, you might reach for omalizumab,” said Dr. Allais, noting that her favored treatment overall is dupilumab.

Risk factors for the development of ICI-induced BP include age > 70, skin cancer, and having an initial response to ICI on first imaging, the latter of which “I find fascinating ... because imaging occurs within the first 12 weeks of treatment, but we don’t see BP popping up until 8.5 months into treatment,” she noted. “So maybe there’s a baseline risk factor that could predispose them.”

Caution with antibiotics: “I try to avoid antibiotics in the ICI setting,” Dr. Allais said, in deference to the “ever-important microbiome.” Studies have demonstrated that the microbiomes of responders to ICI treatment are different from those of nonresponders, she said.

And a “fascinating” study of patients with melanoma undergoing ICI therapy showed not only a higher abundance of Ruminococcaceae bacteria in responders vs nonresponders but a significant impact of dietary fiber. High dietary fiber was associated with significantly improved overall survival in the patients on ICI, with the most pronounced benefit in patients with good fiber intake and no probiotic use. “Even wilder, their T cells changed,” she said. “They had a high expression of genes related to T-cell activation ... so more tumor-infiltrating lymphocytes.”

A retrospective study of 568 patients with stages III and IV melanoma treated with ICI showed that those exposed to antibiotics prior to ICI had significantly worse overall survival than those not exposed to antibiotics. “Think before you give them,” Dr. Allais said. “And try to tell your older patients to eat beans and greens.”

Dr. Allais reported having no relevant disclosures.

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

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

TOPLINE:

Liver transplant improved progression-free survival (PFS) in carefully selected patients with unresectable colorectal liver metastasis; however, the overall survival and recurrence rate benefits did not reach statistical significance.

METHODOLOGY:

• Research has shown promising results for well-selected patients with unresectable colorectal liver metastasis undergoing liver transplant; however, the absence of a suitable comparison group makes it difficult to evaluate the overall effectiveness of this treatment method. 
• Researchers evaluated 33 patients with colorectal cancer and unresectable liver metastasis (mean age, 43.5 years; 52% women) who were eligible for liver transplants, according to validated selection criteria. 
• Of these, 20 patients (61%) underwent a liver transplant, while 13 (39%) declined transplantation and received alternative therapy. 
• Patients who received liver transplants did not undergo regular chemotherapy until recurrence, whereas those in the alternative therapy group continued systemic chemotherapy, with hepatic artery infusion pump placement (n = 5), liver resections (n = 6), and locoregional therapies (n = 6). 
• The main outcomes of the study were overall survival and PFS. 

TAKEAWAY:

• The median follow-up duration was 986 days in the liver transplant group and 657 days in the alternative therapy group. 
• Patients who underwent liver transplant showed higher PFS rates at 1 year (90.0% vs 41.7%), 2 years (72.7% vs 10.4%), and 3 years (36.4% vs 10.4%). The PFS gains were statistically significant (P < .01). 
• Overall survival was also higher in the transplant group — 100% vs 83.9% at 1 year, and 90.0% vs 73.4% at both 2 and 3 years. The differences, however, did not reach significance (P = .12). 
• Liver transplant was associated with a lower recurrence rate (5% vs 23%), which also did not reach significance (P = .28) possibly because of the small patient population. 

IN PRACTICE:

“This study represents the best available data for evaluating alternatives to [liver transplant],” the authors wrote, adding that the patients should be “referred for multidisciplinary evaluation to transplant oncology centers with strict criteria.”

SOURCE:

The study was led by Matthew M. Byrne, MD, Department of Surgery, University of Rochester Medical Center, Rochester, New York, and was published online in JAMA Surgery.

LIMITATIONS:

The patient population was small, making it difficult to interpret statistical significance. The inclusion of patients with financial and social support might limit generalizability. The survival was calculated from the date of transplant or dropout. Additionally, the study did not explore sex-based differences in treatment choice.

DISCLOSURES:

The authors did not disclose any funding information. One author reported holding shares with HistoSonics, not related to the submitted work.

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

Jeffrey S. Weber, MD, PhD, the 2016 winner of the Giants of Cancer Care award in melanoma and a valued contributor to Medscape Oncology, has died.

Dr. Weber, a melanoma and cancer immunotherapy specialist, served as deputy director of the Laura and Isaac Perlmutter Cancer Center at New York University (NYU) Langone Medical Center in New York City. He also held positions as the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at the NYU Grossman School of Medicine, director of the Experimental Therapeutics Program, and co-leader of the Clinical Melanoma Program Board at NYU Langone Health.

Dr. Weber was a principal investigator on many studies, including pivotal clinical drug trials in melanoma and trials focused on managing autoimmune side effects from immunotherapy. He published more than 150 articles in top peer-reviewed journals.

For many years, Dr. Weber hosted the popular “Weber on Oncology” series of video contributions for Medscape Oncology, sharing updates and insights on noteworthy research and breakthroughs in melanoma.

“The Melanoma Research Alliance mourns the passing of Dr. Jeffrey S. Weber, a true pioneer in the field of cancer immunotherapy and an extraordinary leader in melanoma research. His contributions have forever changed the landscape of melanoma treatment, bringing groundbreaking advances from the lab into clinical practice and offering hope to countless patients,” the Melanoma Research Alliance posted on LinkedIn. 

Many X users also shared condolences and memories of Dr. Weber, praising his numerous contributions and accomplishments. 

“[Cancer Research Institute] mourns the loss of Dr. Jeffrey S. Weber ... [a]s an accomplished physician scientist, Dr. Weber drove advances in melanoma research, and played an active role in educating patients about the lifesaving power of immunotherapy,” the Cancer Research Institute posted.

A colleague noted that “[h]e was involved in the early days of cytokine and cell therapy and most recently led studies of personalized vaccines for melanoma patients. ... He was a great friend and colleague to many of us in the melanoma and immunotherapy field and we will remember him as a pioneer, thought leader and compassionate physician.”

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

The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

• Start by sitting and crossing one leg over the other.
• Hug your knee to your chest.
• Focus on keeping your chest up to feel the stretch in the glute.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

• Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
• With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

• Stand in a staggered stance in front of a wall with your arms stretched out.
• Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
• Hold the stretch for 15-30 seconds.
• Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

• While standing, hold onto a countertop or chair back to assist in balance.
• Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
• Gently pull on your ankle to bend your knee as far as possible.
• Maintain the position for 30 seconds.
• Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

• Sit on the front half of a firm chair with your back straight.
• Extend one leg out in front of you with your heel on the floor and your toes pointed up.
• Bend the opposite knee so that your foot is flat on the floor.
• Center your chest over your straight leg.
• Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
• Hold the stretch for 30 seconds.
• Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

• Start by sitting and crossing one leg over the other.
• Hug your knee to your chest.
• Focus on keeping your chest up to feel the stretch in the glute.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

• Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
• With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

• Stand in a staggered stance in front of a wall with your arms stretched out.
• Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
• Hold the stretch for 15-30 seconds.
• Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

• While standing, hold onto a countertop or chair back to assist in balance.
• Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
• Gently pull on your ankle to bend your knee as far as possible.
• Maintain the position for 30 seconds.
• Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

• Sit on the front half of a firm chair with your back straight.
• Extend one leg out in front of you with your heel on the floor and your toes pointed up.
• Bend the opposite knee so that your foot is flat on the floor.
• Center your chest over your straight leg.
• Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
• Hold the stretch for 30 seconds.
• Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.

The more flexible you are as you age, the longer you’re likely to live. That’s the conclusion of a new study that associated increased flexibility in middle age with lower odds of mortality over the next dozen or so years.

The prospective cohort study, which evaluated the flexibility of more than 3100 men and women in Brazil, found body flexibility was strongly and inversely associated with mortality risk over a 13-year follow-up period.

Claudio Gil Araújo, MD, PhD, the research director of the Exercise Medicine Clinic-CLINIMEX in Rio de Janeiro, who led the study, said his group was not surprised by the results. “We found what we expected. Reduced flexibility was related to poor survival,” he said.

The findings, published in the Scandinavian Journal of Medicine & Science in Sports, used data from 2087 men and 1052 women who underwent a medical-functional evaluation at CLINIMEX. They received a body flexibility score, called the Flexindex, based on range of motion in 20 movements in seven joints, with a minimum score of 0 and a maximum score of 80.

Among the 3139 participants, there were 302 deaths (9.6%) during a mean follow-up of 12.9 years, with cardiovascular diseases and cancer the most common underlying causes in men and women, respectively.

“The probability of death during nearly 13 years of follow-up was close to 1% when Flexindex scores exceed 49 for men and 56 for women,” Dr. Araújo told this news organization. “On the other hand, for men and women placed in the lower 10 percent of Flexindex scores, death rates were, respectively, 26.9% and 18.2%.”

Barry Franklin, PhD, director of preventive cardiology and cardiac rehabilitation at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan, and a co-author of the new study, said men with the poorest flexibility were nearly twice as likely to die over the follow-up period than men with high flexibility. Women with the poorest flexibility were almost five times more likely to die than those with high flexibility.
 

Flexibility Assessment and Training

Dr. Araújo opened CLINIMEX in 1994, and since then, its staff of five physicians have evaluated more than 10,000 individuals using the Flexitest. Dr. Araújo has published two previous studies on flexibility. The first showed that the ability to rise from a sitting position on the floor is a strong predictor of longevity, and the second demonstrated that the inability to stand on one leg for at least 10 seconds is linked to an increased risk for death over 7 years.

Dr. Araújo and his colleagues believe the current study is the first to assess the association between levels of body flexibility and mortality. But the observational analysis was unable to establish causality, and therefore, they could not show a definitive mechanism to explain the association between low levels of flexibility and premature mortality.

The authors noted several limitations of their study. The participants were primarily affluent White people, and the researchers did not control for the time of day flexibility was measured or for variables such as diet and physical activity. They also acknowledged reduced flexibility may be a consequence of poor lifestyle habits rather than a causal risk factor for mortality.

Jonathan Bonnet, MD, MPH, an exercise expert at the Stanford Center on Longevity Lifestyle Medicine in California, said the researchers used a more robust evaluation of flexibility than a traditional sit-and-reach test. However, he expressed concern that the primary comparisons were of the upper and lower 10% of performers and that the average differences in Flexindex scores between people who died and those who survived were only a handful of points in an 80-point test.

“People who are not flexible probably have other health-related issues that limit their mobility and those who are very flexible are either genetically different from inflexible individuals or are doing something to maintain or increase their flexibility to a high level,” Dr. Bonnet said. “Not knowing how active or inactive people are at baseline when flexibility was assessed or over the duration of the study limits how confident we can be that flexibility is the cause of mortality.”

Dr. Bonnet, a member of the American College of Lifestyle Medicine, noted that the latest guidelines on physical activity from the US Department of Health and Human Services do not include recommendations on stretching, given the lack of data demonstrating its specific health benefits. While maintaining mobility and range of motion in joints is important for long-term health, he said the new study does not provide sufficient evidence to recommend stretching as a way to reduce mortality.

“Until there are more data that can show a cause-and-effect relationship with stretching and health outcomes, time is better spent doing aerobic and muscle-strengthening activities,” Dr. Bonnet said.

Dr. Franklin said future studies could better account for missing potential confounders like physical activity and whether individuals were taking protective medications, such as aspirin, cholesterol-lowering drugs, or beta-blockers. Studies also are needed to assess whether training-induced gains in flexibility are specifically related to increases in survival and whether their findings apply to people over the age of 65, he said.

The current findings “give us some additional ammo to say, ‘Wow, being more flexible may, in fact, improve long-term survival or outcomes’,” Dr. Franklin said. Regardless, flexibility still “improves quality of life, it improves balance and reduces the potential for falls, and all those things make it worthy of better recognition or appreciation by the general public and clinicians,” he added.

Dr. Araújo said he would like his research to influence people’s health. “While to exercise regularly is advisable, what really matters is to be physically fit and not only in aerobic or strength fitness but also in flexibility,” he said. “The study is adding a new and, I believe, important ‘relevant for survival’ label on flexibility assessment and training.”
 

Recommended Stretches for Increased Mobility and Flexibility

By Matthew Accetta, MS, exercise physiologist at Hospital for Special Surgery in New York City

Hip Hug Stretch

This stretch effectively targets the gluteal muscles, piriformis, and other deep hip rotators, which can become tight from prolonged sitting or lack of movement. Tight hips can contribute to lower back pain. By stretching the hip muscles, you can reduce tension and pressure on the lower back. Regularly performing this stretch helps to improve hip joint mobility, which is essential for maintaining functional movement and preventing stiffness as you age.

• Start by sitting and crossing one leg over the other.
• Hug your knee to your chest.
• Focus on keeping your chest up to feel the stretch in the glute.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Half Kneeling Hip Flexor Stretch

As people age, they often spend more time sitting, which can lead to tight hip flexors. This stretch specifically targets these muscles, helping to alleviate tightness and improve mobility. Tight hip flexors can contribute to poor posture by pulling the pelvis into an anterior tilt, which can lead to lower back pain and other postural issues. Stretching these muscles helps to counteract this effect and promote better posture.

• Kneel on a pad (the side you kneel on is the side being stretched); position the front leg far enough away so the front knee stays behind the toes.
• With a tall posture, engage your abdominals and tuck your tailbone by engaging your glutes until a stretch is felt in the front of the thigh on the kneeling leg.
• Hold for 20-30 seconds.
• Repeat on the opposite side.

Calf Stretch at a Wall

Tight calf muscles can lead to discomfort and limit the range of motion in the ankles. Stretching the calves helps to maintain and improve flexibility in these muscles. Flexible calf muscles contribute to better mobility in the ankles and feet, making daily activities like walking, climbing stairs, and running more comfortable. Tight calves can increase the risk for strains, Achilles tendinitis, and other injuries. Stand facing a wall with your hands on the wall at about eye level. Put the leg you want to stretch about a step behind your other leg.

• Stand in a staggered stance in front of a wall with your arms stretched out.
• Keeping your back heel on the floor, bend your front knee until you feel a stretch in the back leg.
• Hold the stretch for 15-30 seconds.
• Repeat on the opposite side.

Standing Quad Stretch

Regularly stretching the quadriceps helps maintain and improve flexibility in these muscles, which is crucial for overall lower body mobility. Flexible quadriceps are less prone to strains and injuries. Tight quadriceps can contribute to knee pain and discomfort by exerting excessive pressure on the knee joint. Stretching these muscles helps alleviate this pressure and reduce knee pain.

• While standing, hold onto a countertop or chair back to assist in balance.
• Bend your knee by grasping your ankle with one hand and moving your foot toward your buttocks.
• Gently pull on your ankle to bend your knee as far as possible.
• Maintain the position for 30 seconds.
• Repeat on the opposite side.

Seated Hamstring Stretch

Regularly stretching the hamstrings helps maintain and improve their flexibility, which is crucial for the overall mobility of the lower body. Tight hamstrings can contribute to lower back pain by pulling on the pelvis and causing an anterior pelvic tilt. Stretching these muscles can help alleviate tension and reduce back pain. Hamstring flexibility helps to contribute to a better range of motion in the hip and knee joints, making daily activities such as walking, bending, and reaching easier.

• Sit on the front half of a firm chair with your back straight.
• Extend one leg out in front of you with your heel on the floor and your toes pointed up.
• Bend the opposite knee so that your foot is flat on the floor.
• Center your chest over your straight leg.
• Slowly lean forward at the hips until you feel a stretch in the back of your thigh.
• Hold the stretch for 30 seconds.
• Slowly return to your original position and repeat on the opposite side.

The sources in this story reported no relevant financial conflicts of interest.

A version of this article appeared on Medscape.com.