A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

A high-profile, Washington-based consumer advocacy group is calling for the removal of the U.S. Food and Drug Administration’s acting commissioner and two other top officials, saying that the agency’s approval of the Alzheimer’s drug aducanumab (Aduhelm, Biogen) was “reckless.”

In a letter to the U.S. Department of Health and Human Services Secretary Xavier Becerra, Michael A. Carome, MD, director of Public Citizen’s Health Research Group, said: “The FDA’s decision to approve aducanumab for anyone with Alzheimer’s disease, regardless of severity, showed a stunning disregard for science, eviscerated the agency’s standards for approving new drugs, and ranks as one of the most irresponsible and egregious decisions in the history of the agency.”

Public Citizen urged Mr. Becerra to seek the resignations or the removal of the three FDA officials it said were most responsible for the approval – Acting FDA Commissioner Janet Woodcock, MD; Center for Drug Evaluation and Research (CDER) Director Patrizia Cavazzoni, MD; and CDER’s Office of Neuroscience Director Billy Dunn, MD.

“This decision is a disastrous blow to the agency’s credibility, public health, and the financial sustainability of the Medicare program,” writes Dr. Carome, noting that Biogen said it would charge $56,000 annually for the infusion.

Aaron Kesselheim, MD, one of three FDA Peripheral and Central Nervous System Drugs advisory committee members who resigned in the wake of the approval, agreed with Public Citizen that the agency’s credibility is suffering.

“The aducanumab decision is the worst example yet of the FDA’s movement away from its high standards,” Dr. Kesselheim, a professor of medicine at Harvard Medical School, Boston, and Harvard colleague Jerry Avorn, MD, wrote in the New York Times on June 15.

“As physicians, we know well that Alzheimer’s disease is a terrible condition,” they wrote. However, they added, “approving a drug that has such poor evidence that it works and causes such worrisome side effects is not the solution.”

In his resignation letter, Dr. Kesselheim said he had also been dismayed by the agency’s 2016 approval of eteplirsen (Exondys 51, Sarepta Therapeutics) for Duchenne muscular dystrophy. In both the eteplirsen and aducanumab approvals, the agency went against its advisers’ recommendations, Dr. Kesselheim said.
 

Advocates who backed approval decry cost

Aducanumab had a rocky road to approval but had unwavering backing from the Alzheimer’s Association and at least one other organization, UsAgainstAlzheimer’s.

The Alzheimer’s Association was particularly outspoken in its support and, in March, was accused of potential conflict of interest by Public Citizen and several neurologists because the association accepted at least $1.4 million from Biogen and its partner Eisai since fiscal year 2018.

The association applauded the FDA approval but, a few days later, expressed outrage over the $56,000-a-year price tag.

“This price is simply unacceptable,” the Alzheimer’s Association said in the statement. “For many, this price will pose an insurmountable barrier to access, it complicates and jeopardizes sustainable access to this treatment, and may further deepen issues of health equity,” the association said, adding, “We call on Biogen to change this price.”

UsAgainstAlzheimer’s also expressed concerns about access, even before it knew aducanumab’s price.  

“Shockingly, Medicare does not reimburse patients for the expensive PET scans important to determine whether someone is appropriate for this drug,” noted George Vradenburg, chairman and cofounder of the group, in a June 7 statement. “We intend to work with Biogen and Medicare to make access to this drug affordable for every American who needs it,” Mr. Vradenburg said.

Dr. Carome said the advocates’ complaints were hard to fathom.

“This should not have come as a surprise to anyone,” Dr. Carome said, adding that “it’s essentially the ballpark figure the company threw out weeks ago.”

“Fifty-six-thousand-dollars is particularly egregiously overpriced for a drug that doesn’t work,” Dr. Carome said. “If the [Alzheimer’s Association] truly finds this objectionable, hopefully they’ll stop accepting money from Biogen and its partner Eisai,” he added.

“The Alzheimer’s Association is recognizing that the genie is out of the bottle and that they are going to have trouble reining in the inevitable run-away costs,” said Mike Greicius, MD, MPH, associate professor of neurology at Stanford University’s Wu Tsai Neurosciences Institute, Stanford, California.

“In addition to the eye-popping annual cost that Biogen has invented, I hope the Alzheimer’s Association is also concerned about the dangerously loose and broad FDA labeling which does not require screening for amyloid-positivity and does not restrict use to the milder forms of disease studied in the Phase 3 trials,” Dr. Greicius said.

Another advocacy group, Patients For Affordable Drugs, commended the Alzheimer’s Association. Its statement “was nothing short of courageous, especially in light of the Alzheimer’s Association’s reliance on funding from drug corporations, including Biogen,” said David Mitchell, a cancer patient and founder of Patients For Affordable Drugs, in a statement.

Mr. Mitchell said his members “stand with the Alzheimer’s Association in its denunciation of the price set by Biogen” and called for a new law that would allow Medicare to negotiate drug prices.

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

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

Gradually, we are emerging from the chaos, isolation, and anxiety of COVID-19. As the Centers for Disease Control and Prevention adjusts its recommendations and vaccinations become more widely available, our communities are beginning to return to normalcy. We are encouraged to put aside our masks if vaccinated and rejoin society, to venture out with less hesitancy and anxiety. As family and friends reunite, memories of confusion, frustration, and fear are beginning to fade to black. Despite the prevailing belief that we should move on, look forward, and remember the past to safeguard our future, remnants of the pandemic remain.

shironosov/Getty Images

Unvaccinated individuals, notably children under the age of 12, are quite significant in number. The use of telehealth is now standard practice.

For several years, we were warned about the looming “mental health crisis.” The past year has demonstrated that a crisis no longer looms – it has arrived. Our patients can reveal the vulnerability COVID-19 has wrought – from the devastation of lives lost, supply shortages, loss of employment and financial stability – to a lack of access to computers and thereby, the risk of educational decline. Those factors, coupled with isolation and uncertainty about the future, have led to an influx of individuals with anxiety, depression, and other mood disorders seeking mental health treatment.
 

Doctors, others suffering

As result of a medical culture guided by the sacred oath to which care, compassion, and dedication held as true in ancient Greece as it does today, the focus centers on those around us – while signs of our own weariness are waved away as “a bad day.” Even though several support groups are readily available to offer a listening ear and mental health physicians who focus on the treatment of health care professionals are becoming more ubiquitous, the vestiges of past doctrine remain.

In this modern age of medical training, there is often as much sacrifice as there is attainment of knowledge. This philosophy is so ingrained that throughout training and practice one may come across colleagues experiencing an abundance of guilt when leave is needed for personal reasons. We are quick to recommend such steps for our patients, family, and friends, but hesitant to consider such for ourselves. Yet, of all the lessons this past year has wrought, the importance of mental health and self-care cannot be overstated. This raises the question: How do we incorporate wellness into our routines while navigating the complexity of medicine?

It is vital to accept our humanity as something not to repair, treat, or overcome but to understand. There is strength and power in vulnerability. If we do not perceive and validate this process within ourselves, how can we do so for others? In other words, the oxygen mask must be placed on us first before we can place it on anyone else – patients or otherwise.

Chiefly and above all else, the importance of identifying individual signs of stress is essential. Where do you hold tension? Are you prone to GI distress or headaches when taxed? Do you tend toward irritability, apathy, or exhaustion?

Once this is determined, it is important to assess your stress on a numerical scale, such as those used for pain. Are you a 5 or an 8? Finally, are there identifiable triggers or reliable alleviators? Is there a time of day or day of the week that is most difficult to manage? Can you anticipate potential stressors? Understanding your triggers, listening to your body, and practicing the language of self is the first step toward wellness.

Following introspection and observation, the next step is inventory. Take stock of your reserves. What replenishes? What depletes? What brings joy? What brings dread? Are there certain activities that mitigate stress? If so, how much time do they entail? Identify your number on a scale and associate that number with specific strategies or techniques. Remember that decompression for a 6 might be excessive for a 4. Furthermore, what is the duration of these feelings? Chronic stressors may incur gradual change verses sudden impact if acute. Through identifying personal signs, devising and using a scale, as well as escalating or de-escalating factors, individuals become more in tune with their bodies and therefore, more likely to intervene before burnout takes hold.

With this process well integrated, one can now consider stylized approaches for stress management. For example, those inclined toward mindfulness practices may find yoga, meditation, and relaxation exercises beneficial. Others may thrive on positive affirmations, gratitude, and thankfulness. While some might find relief in physical activity, be it strenuous or casual, the creative arts might appeal to those who find joy in painting, writing, or doing crafts. In addition, baking, reading, dancing, and/or listening to music might help lift stress.

Along with those discoveries, or in some cases, rediscoveries, basic needs such as dietary habits and nutrition, hydration, and sleep are vital toward emotional regulation, physiological homeostasis, and stress modulation. Remember HALT: Hungry, Angry, Lonely, Tired, Too hot, Too cold, Sad or Stressed. Those strategies are meant to guide self-care and highlight the importance of allowing time for self-awareness. Imagine yourself as if you are meeting a new patient. Establish rapport, identify symptoms, and explore options for treatment. When we give time to ourselves, we can give time more freely to others. With this in mind, try following the 5-minute wellness check that I formulated:

1. How am I feeling? What am I feeling?

2. Assess HALTS.

3. Identify the number on your scale.

4. Methods of quick de-escalation:

• Designate and schedule personal time.
• Write down daily goals.
• Repeat positive affirmations or write down words of gratitude.
• Use deep breathing exercises.
• Stretch or take a brief walk.
• Engage in mindfulness practices, such as meditation.

Once we develop a habit of monitoring, assessing, and practicing self-care, the process becomes more efficient and effective. Think of the way a seasoned attending can manage workflow with ease, compared with an intern. Recognizing signs and using these strategies routinely can become a quick daily measure of well-being.
 

Dr. Thomas is a board-certified adult psychiatrist with interests in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. Dr. Thomas has no conflicts of interest.

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

A report by the American Medical Association’s medical education advisory body points to systemic racism or other systems of oppression as causing a lack of representation, exclusion, and marginalization in medical education and medicine.

The report received overwhelming support at the House of Delegates, the AMA’s legislative policy making body, during an online meeting held June 13.

The Council on Medical Education’s report recommends that the AMA acknowledge the harm caused by the Flexner Report, which was issued in 1910 and has since shaped medical education. The Flexner Report caused harm not only to historically Black medical schools, but also to physician workforce diversity and to the clinical outcomes of minority and marginalized patients, according to the medical education advisory body.

The council also recommended conducting a study on medical education with a focus on health equity and racial justice, improving diversity among healthcare workers, and fixing inequitable outcomes from minorities and marginalized patient populations.

The report comes on the heels of the resignation of JAMA editor-in-chief Howard Bauchner, MD, and another high-ranking editor following a February podcast on systemic racism in medicine. The AMA has since released a strategic plan addressing racism and health inequity that has divided membership.
 

Flexner Report’s effect on physician diversity

The Council on Medical Education’s report observed that as a result of the Flexner Report’s recommendations, 89 medical schools, including 5 of the 7 existing medical schools training Black physicians, were closed because they didn’t meet the report’s standards. In addition, the report created a limited role for Black physicians while “hint[ing] that Black physicians possessed less potential and ability than their White counterparts,” read the Council’s report.

In addition to consigning the role of the Black physician to “educating the [Black] race to know and to practice fundamental hygienic principles,” the Flexner Report also observed that “a well-taught negro sanitarian will be immensely useful,” per the Council’s report.

The impact of the closure of medical schools training Black physicians was dramatic. According to the Council’s report, in 1964, 93% of medical students in the United States were men and 97% of those students were non-Hispanic White.

Today, 56% of physicians identify as White, 17% as Asian, 6% as Hispanic, and 5% as Black or African American, per the Association of American Medical Colleges; nearly 14% of active physicians didn’t report their race in the survey. By means of contrast, the U.S. population in 2019 was 60% White, 19% Latino/Hispanic, 13% Black or African American, and 6% Asian American, according to the Brookings Institute.

Abraham Flexner, who wrote the Flexner Report, is often referred to as the “father of modern medical education,” according to the AAMC. In November, the AAMC observed that the Flexner Report contained racist and sexist ideas and that his work contributed to the closure of historically Black medical schools. Both statements were included in AAMC’s announcement about the removal of Flexner’s name from its most prestigious award. As of January, the award is now called the AAMC Award for Excellence in Medical Education.
 

Pathway programs can increase diversity

Pathway programs, which leverage targeted milestones along the journey to becoming a physician in order to increase diversity, were an area of focus in the council’s report. These programs “can exert a meaningful, positive effect on student outcomes and increase diversity across various levels of educational settings,” according to its report.

Centers of Excellence, which provides grants for mentorship and training programs, is one of many pathway programs. During the 2018-2019 academic year, Centers of Excellence supported more than 1,300 trainees – 99% of them were underrepresented minorities and 64% came from financially or educationally disadvantaged backgrounds. In 2006, federal funding was cut to these programs and the number of Centers of Excellence fell.

Still, the report cites the passage of federal funding in 2020 of $50 million for public institutions of higher education that train physicians; educational institutions in states with a projected primary care shortage in 2025 are given priority in the grant-funding process.
 

AMA council’s report garners support from delegates

Delegates voiced overwhelming support of the council’s report during the June 13 meeting. Lou Edje, MD, a Perrysburgh, Ohio–based family physician, voiced strong support for the council’s report, in particular its recommendations that recognize the harm caused by the Flexner Report. Dr. Edje observed that the Flexner Report, with its elimination of five of seven Black medical schools, “[set] back admissions of Black students into medicine by 50 years.”

“Empathy is what we are called to have as physicians. I implore you to simply substitute your ethnicity into these quotes to help understand the historic need for health equity in medicine today. This CME report is part of the antidote to Flexner. We support [it] fully,” concluded Dr. Edje, who spoke for the Great Lakes States Coalition of the AMA.

Rohan Khazanchi, a medical student at the University of Nebraska, Omaha, and a member of the council, said, “Our broad attempt with this report was twofold: to fill gaps in AMA policy with evidence-based recommendations which could improve diversity in our health workforce and, second, to enhance our organization’s vision for truth, reconciliation, and healing to redress the historic marginalization of minoritized physicians in medicine.”

According to an AMA spokesperson, the House of Delegates will vote on this and other policies this week, after which the policies are considered final.

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

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Advances in photobiomodulation have propelled the use of therapeutic applications in a variety of medical specialties, according to Juanita J. Anders, PhD.

During the annual conference of the American Society for Laser Medicine and Surgery, Dr. Anders, professor of anatomy, physiology, and genetics at the Uniformed Services University of the Health Sciences, Bethesda, Md., defined photobiomodulation (PBM) as the mechanism by which nonionizing optical radiation in the visible and near-infrared spectral range is absorbed by endogenous chromophores to elicit photophysical and photochemical events at various biological scales. Photobiomodulation therapy (PBMT) involves the use of light sources including lasers, LEDs, and broadband light, that emit visible and/or near-infrared light to cause physiological changes in cells and tissues and result in therapeutic benefits.

In dermatology, LED light therapy devices are commonly used for PBMT in wavelengths that range from blue (415 nm) and red (633 nm) to near infrared (830 nm). “Often, when PBMT is referred to by dermatologists it’s called LED therapy or LED light therapy,” Dr. Anders noted. “Some people are under the impression that this is different from PBMT. But remember: It’s not the device that’s producing the photons that is clinically relevant, but it’s the photons themselves. In both cases, the same radiances and fluence ranges are being used and the mechanisms are the same, so it’s all PBMT.”

The therapy is used to treat a wide variety of medical and aesthetic disorders including acne vulgaris, psoriasis, burns, and wound healing. It has also been used in conjunction with surgical aesthetic and resurfacing procedures and has been reported to reduce erythema, edema, bruising, and days to healing. It’s been shown that PBMT stimulates fibroblast proliferation, collagen synthesis, and extracellular matrix resulting in lifting and tightening lax skin.

According to Dr. Anders, French dermatologists Linda Fouque, MD, and Michele Pelletier, MD, performed a series of in vivo and in vitro studies in which they tested the effects of yellow and red light for skin rejuvenation when used individually or in combination. “They found that fibroblasts and keratinocytes in vitro had great improvement in their morphology both with the yellow and red light, but the best improvement was seen with combination therapy,” Dr. Anders said. “This held true in their work looking at epidermal and dermal markers in the skin, where they found the best up-regulation in protein synthesis of such markers as collagens and fibronectin were produced when a combination wavelength light was used.”

Oral mucositis and pain

PBMT is also being used to treat oral mucositis (OM), a common adverse response to chemotherapy and/or radiation therapy, which causes pain, difficulty in swallowing and eating, and oral ulceration, and often interrupts the course of treatments. Authors of a recently published review on the risks and benefits of PBMT concluded that there is consistent evidence from a small number of high-quality studies that PBMT can help prevent the development of cancer therapy–induced OM, reduce pain intensity, as well as promote healing, and enhance patient quality of life.

“They also cautioned that, due to the limited long-term follow-up of patients, there is still concern for the potential long-term risks of PBMT in cancer cell mutation and amplification,” Dr. Anders said. “They advised that PBMT should be used carefully when the irradiation beam is in the direction of the tumor zone.”

Using PBMT for modulation of pain is another area of active research. Based on work from the laboratory of Dr. Anders and others, there are two methods to modulate pain. The first is to target tissue at irradiances below 100 mW/cm².

“In my laboratory, based on in vivo preclinical animal models of neuropathic pain, we used a 980-nm wavelength laser at 43.25 mW/cm² transcutaneously delivered to the level of the nerve for 20 seconds,” said Dr. Anders, who is a past president of the ASLMS. “Essentially, we found that the pain was modulated by reducing sensitivity to mechanical stimulation and also by causing an anti-inflammatory shift in microglial and macrophage phenotype in the dorsal root ganglion and spinal cord of affected segments.”

The second way to modulate pain, she continued, is to target tissue at irradiances above 250 mW/cm². She and her colleagues have conducted in vitro and in vivo studies, which indicate that treatment with an irradiance/fluence rate at 270 mW/cm² or higher at the nerve can rapidly block pain transmission.

“In vitro, we found that if we used an 810-nm wavelength light at 300 mW/cm², we got a disruption of microtubules in the DRG neurons in culture, specifically the small neurons, the nociceptive fibers, but we did not affect the proprioceptive fibers unless we increased the length of the treatment,” she said. “We essentially found the same thing in vivo in a rodent model of neuropathic pain.”

In a pilot study, Dr. Anders and coauthors examined the efficacy of laser irradiation of the dorsal root ganglion of the second lumbar spinal nerve for patients with chronic back pain.

They found that PBMT effectively reduced back pain equal to the effects of lidocaine.

Based on these two irradiation approaches of targeting tissue, Dr. Anders recommends that a combination therapy be used to modulate neuropathic pain going forward. “This approach would involve the initial use of a high-irradiance treatment [at least 250 mW/cm²] at the nerve to block the pain transmission,” she said. “That treatment would be followed by a series of low-irradiance treatments [10-100 mW/cm²] along the course of the involved nerve to alter chronic pathology and inflammation.”
 

Potential applications in neurology

Dr. Anders also discussed research efforts under way involving transcranial PBMT: the delivery of near-infrared light through the tissues of the scalp and skull to targeted brain regions to treat neurologic injuries and disorders. “There have been some exciting results in preclinical animal work and in small clinical pilot work that show that there could be possible beneficial effects in Parkinson’s disease, Alzheimer’s disease, depression, and improvement in cognition and memory after a brain injury, such as a TBI,” she said.

“Initially, though, there were a lot of questions about whether you could really deliver light to the brain through the scalp. In my laboratory, we used slices of nonfixed brain and found that the sulci within the human brain act as light-wave guides. We used an 808-nm near-infrared wavelength of light, so that the light could penetrate more deeply.” Using nonfixed cadaver heads, where the light was applied at the scalp surface, Dr. Anders and colleagues were able to measure photons down to the depth of 4 cm. “It’s generally agreed now, though, that it’s to a maximum depth of 2.5-3 cm that enough photons are delivered that would cause a beneficial therapeutic effect,” she said.

Dr. Anders disclosed that she has received equipment from LiteCure, grant funding from the Department of Defense, and that she holds advisory board roles with LiteCure and Neurothera. She has also served in leadership roles for the Optical Society and holds intellectual property rights for the Henry M. Jackson Foundation for the Advancement of Military Medicine.

[email protected]

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Chilblain-like lesions seen in adolescents during the COVID-19 pandemic are nonischemic and not related to systemic or localized SARS-CoV-2 infection, suggests a case series from Italy.

These lesions are “most likely are benign” and resolve on their own after 2-6 weeks, Valentina Discepolo, MD, PhD, University of Naples Federico II, told this news organization.

“They do not seem to be the manifestation of systemic inflammatory or autoimmune phenomena. According to our experience, they should not require a SARS-CoV-2–specific molecular or serological test since in all cases in our series they were negative,” said Dr. Discepolo.

The study was published online June 10, 2021, in JAMA Network Open.
 

‘COVID toes’ a fallacy?

The temporal association between the COVID-19 pandemic and the increasing number of chilblain-like lesions has led some in the media to call it “COVID toes,” the investigators wrote. However, data on the association with SARS-CoV-2 are controversial.

For this report, Dr. Discepolo and colleagues evaluated 17 adolescents who presented with chilblain-like lesions of the toes during the first wave of the pandemic in southern Italy.

None had evidence of current, past, or local SARS-CoV-2 infection.

“In our experience, chilblain-like lesions are not a manifestation of COVID-19, as shown by negative serological and molecular specific for SARS-CoV2,” Dr. Discepolo said in an interview.

The lesions were bilaterally distributed in 16 adolescents (94.1%) and heel skin was involved in 7 (41.2%). Ulceration complicated one patient during the active phase of the disease, and desquamation developed over time in three patients (17.6%). Only two patients (11.8%) had concurrent involvement of the fingers.

Self-administered therapies included topical antibiotics and/or corticosteroids, disinfectants, and antifungal agents; systemic antibiotics or corticosteroids were used rarely.

None of the therapies substantially changed the course of the lesions. Duration was “extremely variable,” ranging from 49 to 145 days; however, at follow-up, all patients had full resolution.

Almost invariably, the lesions were characterized by a triad of red dots, white rosettes, and white streaks on an erythematous background, the investigators reported.

In more than half the patients (56%), red dots often appeared as dotted and comma-shaped congested vessels that surrounded the rosettes in the early stage of the lesions. In later stages, red dots were still present, but the rosettes had disappeared.

Although found inconsistently in inflammatory cutaneous conditions, these three signs do not characterize the dermoscopic picture of perniosis, suggesting a distinct disease process, the investigators said.

 

Don’t blame it on ischemia, clots

Histologic analysis revealed “remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate,” they noted.

Punch biopsy of the involved skin mostly showed endothelial hyperplasia, mild lymphocytic infiltrate, and vessels’ architecture disruption with no papillary dermal edema or eosinophilic or neutrophilic infiltrate.

Pathology did not reveal any ischemic changes, which argues against systemic vasculopathy, Farzam Gorouhi, MD, from Kaiser Permanente, South Sacramento Medical Center, noted in a linked editorial. “Thus, this study provides further evidence against the thromboembolic nature of the presented pattern in adolescents during the COVID-19 pandemic.”

Results of capillaroscopy, used to investigate structural changes in peripheral microcirculation, were either completely normal or showed rare ectasias, supporting a lack of systemic inflammatory process.

“The lack of capillaroscopic features of a major vasculopathic event in the study by Discepolo et al. argues against the ischemic nature of this disease and, thus, indicates that this presentation is not associated with systemic ischemia or an embolic event,” Dr. Gorouhi noted.

Chilblain-like lesions have been one of the most commonly described cutaneous manifestations during the COVID-19 pandemic, but their etiopathogenesis, including the role of SARS-CoV-2, has remained elusive, the investigators wrote.

The findings in this case series do not support the association of the lesions with SARS-CoV-2 infection, they concluded.

The fact that only three new cases of chilblain-like lesions were reported during the highest peaks of the pandemic further supports a lack of association with SARS-CoV-2 infection, they noted.

In addition, none of these patients tested positive for SARS-CoV-2 and all three cases during the second wave occurred in the winter months, suggesting that exposure to the cold might, at least in some cases, trigger the skin lesions, the investigators said.

In line with this hypothesis, seven of the adolescents in this case series (41.2%) relapsed during the winter months while again testing negative for SARS-CoV-2.

“We believe that lifestyle modifications [reduced physical activity, microtraumatisms caused by walking barefoot at home] during the first strict lockdown played a role, likely promoting a local inflammatory process promoted by vascular stasis that led in genetically susceptible individuals to the onset of these lesions,” Dr. Discepolo said in an interview.

This research had no specific funding. The investigators and Dr. Gorouhi declared no relevant conflicts of interest.
 

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

Cardiovascular disease is the leading cause of women’s death in the United States, accounting for 1 in every 5 female deaths per year according to the Centers for Disease Control and Prevention. Most risk factors for cardiovascular disease are modifiable. With a disease so prevalent in women’s health, obstetricians and gynecologists can assist patients in modifying these risk factors. This, however, is easier said than done.

One of the rate-limiting steps in assisting patients is the process of identifying an individual’s risk factors. This can be a time-consuming task in a women’s health appointment that is already busy with ObGyn-specific concerns, but technology can assist us.

Cardiovascular health app considerations

Many smartphone applications and websites are available that can alleviate the time constraints for identifying these individual modifiable risk factors. When evaluating cardiovascular risk factor apps for patients, keep these qualities (as outlined in the ACOG-recommended rubric) in mind: design, functionality, usefulness, and accuracy.

The patient-centered resources that assist women in identifying cardiovascular risk factors and that provide tools to positively impact these risk factors through lifestyle changes can help women achieve improved cardiovascular health. Recommendations include 1) manage blood pressure, 2) control cholesterol, 3) reduce blood sugar, 4) get active, 5) eat better, 6) lose weight, and 7) stop smoking.

National organizations’ smartphone apps guide the patient through a handful of questions about their current lifestyle, gender, age, and basic laboratory values. Their individual “heart health” results of these questions distribute the 7 risk factors to 3 categories based on the need to focus, improve, or celebrate. Through nonthreatening videos, patients can improve their scores themselves and bring the areas they need to focus, or improve, to their ObGyn’s attention for further assistance.

While adding one more task to an already busy practice can seem daunting, there are great technology resources that can be leveraged to successfully address this important health metric. By using the ACOG-recommended rubric and focusing on the app characteristics identified above, you can find one that works best for you and your patients and incorporate it into your practice today. ●

Cardiovascular disease is the leading cause of women’s death in the United States, accounting for 1 in every 5 female deaths per year according to the Centers for Disease Control and Prevention. Most risk factors for cardiovascular disease are modifiable. With a disease so prevalent in women’s health, obstetricians and gynecologists can assist patients in modifying these risk factors. This, however, is easier said than done.

One of the rate-limiting steps in assisting patients is the process of identifying an individual’s risk factors. This can be a time-consuming task in a women’s health appointment that is already busy with ObGyn-specific concerns, but technology can assist us.

Cardiovascular health app considerations

Many smartphone applications and websites are available that can alleviate the time constraints for identifying these individual modifiable risk factors. When evaluating cardiovascular risk factor apps for patients, keep these qualities (as outlined in the ACOG-recommended rubric) in mind: design, functionality, usefulness, and accuracy.

The patient-centered resources that assist women in identifying cardiovascular risk factors and that provide tools to positively impact these risk factors through lifestyle changes can help women achieve improved cardiovascular health. Recommendations include 1) manage blood pressure, 2) control cholesterol, 3) reduce blood sugar, 4) get active, 5) eat better, 6) lose weight, and 7) stop smoking.

National organizations’ smartphone apps guide the patient through a handful of questions about their current lifestyle, gender, age, and basic laboratory values. Their individual “heart health” results of these questions distribute the 7 risk factors to 3 categories based on the need to focus, improve, or celebrate. Through nonthreatening videos, patients can improve their scores themselves and bring the areas they need to focus, or improve, to their ObGyn’s attention for further assistance.

While adding one more task to an already busy practice can seem daunting, there are great technology resources that can be leveraged to successfully address this important health metric. By using the ACOG-recommended rubric and focusing on the app characteristics identified above, you can find one that works best for you and your patients and incorporate it into your practice today. ●

Cardiovascular disease is the leading cause of women’s death in the United States, accounting for 1 in every 5 female deaths per year according to the Centers for Disease Control and Prevention. Most risk factors for cardiovascular disease are modifiable. With a disease so prevalent in women’s health, obstetricians and gynecologists can assist patients in modifying these risk factors. This, however, is easier said than done.

One of the rate-limiting steps in assisting patients is the process of identifying an individual’s risk factors. This can be a time-consuming task in a women’s health appointment that is already busy with ObGyn-specific concerns, but technology can assist us.

Cardiovascular health app considerations

Many smartphone applications and websites are available that can alleviate the time constraints for identifying these individual modifiable risk factors. When evaluating cardiovascular risk factor apps for patients, keep these qualities (as outlined in the ACOG-recommended rubric) in mind: design, functionality, usefulness, and accuracy.

The patient-centered resources that assist women in identifying cardiovascular risk factors and that provide tools to positively impact these risk factors through lifestyle changes can help women achieve improved cardiovascular health. Recommendations include 1) manage blood pressure, 2) control cholesterol, 3) reduce blood sugar, 4) get active, 5) eat better, 6) lose weight, and 7) stop smoking.

National organizations’ smartphone apps guide the patient through a handful of questions about their current lifestyle, gender, age, and basic laboratory values. Their individual “heart health” results of these questions distribute the 7 risk factors to 3 categories based on the need to focus, improve, or celebrate. Through nonthreatening videos, patients can improve their scores themselves and bring the areas they need to focus, or improve, to their ObGyn’s attention for further assistance.

While adding one more task to an already busy practice can seem daunting, there are great technology resources that can be leveraged to successfully address this important health metric. By using the ACOG-recommended rubric and focusing on the app characteristics identified above, you can find one that works best for you and your patients and incorporate it into your practice today. ●

Diabetes mellitus affects 10% of the US population, and as many as one-third of US adults have prediabetes, according to the National Diabetes Statistics Report 2020 from the Centers for Disease Control and Prevention. While diabetes is associated with significant long-term morbidity and mortality, with early identification and interventions, lifestyle modifications can significantly improve long-term health.

As with obesity (see “Focus on obesity” in OBG Management, May 2021), it is difficult to address lifestyle modifications with patients who have diabetes. However, many apps can be leveraged to aid physicians in this effort.

Diabetes app considerations

Obstetrician-gynecologists can play a pivotal role in helping to screen women for diabetes. When applying the ACOG-recommended rubric to evaluate the quality of an app that is targeted to address screening and diagnosing diabetes, it’s important to consider the app’s timeliness, authority, usefulness, and design.

There are point-of-care apps that include a few simple questions that can quickly identify which women should be screened. Some apps combine screening questions with testing results to streamline screening and diagnosis of diabetes and prediabetes. These apps also provide clinical content to help physicians educate, initiate, and even treat diabetes if they desire.

A wealth of patient-centered apps are available to help patients address a diagnosis of diabetes. Apps that provide real-time feedback, motivational features to engage the user, and links to nutritional, fitness, and diabetic goals provide a woman with a comprehensive and personalized experience that can considerably improve health.

By incorporating apps and engaging with our patients on app technology, ObGyns can successfully partner with women to decrease morbidity with respect to diabetes mellitus and its long-term implications. ●

Diabetes mellitus affects 10% of the US population, and as many as one-third of US adults have prediabetes, according to the National Diabetes Statistics Report 2020 from the Centers for Disease Control and Prevention. While diabetes is associated with significant long-term morbidity and mortality, with early identification and interventions, lifestyle modifications can significantly improve long-term health.

As with obesity (see “Focus on obesity” in OBG Management, May 2021), it is difficult to address lifestyle modifications with patients who have diabetes. However, many apps can be leveraged to aid physicians in this effort.

Diabetes app considerations

Obstetrician-gynecologists can play a pivotal role in helping to screen women for diabetes. When applying the ACOG-recommended rubric to evaluate the quality of an app that is targeted to address screening and diagnosing diabetes, it’s important to consider the app’s timeliness, authority, usefulness, and design.

There are point-of-care apps that include a few simple questions that can quickly identify which women should be screened. Some apps combine screening questions with testing results to streamline screening and diagnosis of diabetes and prediabetes. These apps also provide clinical content to help physicians educate, initiate, and even treat diabetes if they desire.

A wealth of patient-centered apps are available to help patients address a diagnosis of diabetes. Apps that provide real-time feedback, motivational features to engage the user, and links to nutritional, fitness, and diabetic goals provide a woman with a comprehensive and personalized experience that can considerably improve health.

By incorporating apps and engaging with our patients on app technology, ObGyns can successfully partner with women to decrease morbidity with respect to diabetes mellitus and its long-term implications. ●

Diabetes mellitus affects 10% of the US population, and as many as one-third of US adults have prediabetes, according to the National Diabetes Statistics Report 2020 from the Centers for Disease Control and Prevention. While diabetes is associated with significant long-term morbidity and mortality, with early identification and interventions, lifestyle modifications can significantly improve long-term health.

As with obesity (see “Focus on obesity” in OBG Management, May 2021), it is difficult to address lifestyle modifications with patients who have diabetes. However, many apps can be leveraged to aid physicians in this effort.

Diabetes app considerations

Obstetrician-gynecologists can play a pivotal role in helping to screen women for diabetes. When applying the ACOG-recommended rubric to evaluate the quality of an app that is targeted to address screening and diagnosing diabetes, it’s important to consider the app’s timeliness, authority, usefulness, and design.

There are point-of-care apps that include a few simple questions that can quickly identify which women should be screened. Some apps combine screening questions with testing results to streamline screening and diagnosis of diabetes and prediabetes. These apps also provide clinical content to help physicians educate, initiate, and even treat diabetes if they desire.

A wealth of patient-centered apps are available to help patients address a diagnosis of diabetes. Apps that provide real-time feedback, motivational features to engage the user, and links to nutritional, fitness, and diabetic goals provide a woman with a comprehensive and personalized experience that can considerably improve health.

By incorporating apps and engaging with our patients on app technology, ObGyns can successfully partner with women to decrease morbidity with respect to diabetes mellitus and its long-term implications. ●

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

Last month we converged virtually for our annual conference, SHM Converge – the second time since the start of the coronavirus pandemic. We are thankful for innovations and advancements in technology that have allowed the world, including SHM, to continue connecting us all together. And yet, 18 months in, having forged new roads, experienced unique and life-changing events, we long for the in-person human connection that allows us to share a common experience. At a time of imperatives in our world – a global pandemic, systemic racism, and deep geopolitical divides – more than ever, we need to converge. Isolation only festers, deepening our divisions and conflicts.

In high school, I read Robert Frost’s poem “The Road Not Taken” and clung to the notion of diverging roads and choosing the road less traveled. Like most young people, my years since reading the poem were filled with attempts at forging new paths and experiencing great things – and yet, always feeling unaccomplished. Was Oscar Wilde right when he wrote: “Life imitates Art far more than Art imitates Life?” After all, these past 18 months, we have shared in the traumas of our times, and still, we remain isolated and alone. Our diverse experiences have been real, both tragic and heroic, from east to west, city to country, black to white, and red to blue.

At SHM, it’s time to converge and face the great challenges of our lifetime. A deadly pandemic continues to rage around the world, bringing unprecedented human suffering and loss of lives. In its wake, this pandemic also laid bare the ugly face of systemic racism, brought our deepest divisions to the surface – all threatening the very fabric of our society. This pandemic has been a stress test for health care systems, revealing our vulnerabilities and expanding the chasm of care between urban and rural communities, all in turn worsening our growing health disparities. This moment needs convergence to rekindle connection and solidarity.

Scholars do not interpret “The Road Not Taken” as a recommendation to take the road less traveled. Instead, it is a suggestion that the diverging roads lead to a common place having been “worn about the same” as they “equally lay.” It is true that our roads are unique and shape our lives, but so, too, does the destination and common place our roads lead us to. At that common place, during these taxing times, SHM enables hospitalists to tackle these great challenges.

For over 2 decades of dynamic changes in health care, SHM has been the workshop where hospitalists converged to sharpen clinical skills, improve quality and safety, develop acute care models inside and outside of hospitals, advocate for better health policy and blaze new trails. Though the issues evolved, and new ones emerge, today is no different.

Indeed, this is an historic time. This weighted moment meets us at the crossroads. A moment that demands synergy, cooperation, and creativity. A dynamic change to health care policy, advances in care innovation, renewed prioritization of public health, and rich national discourse on our social fabric; hospitalists are essential to every one of those conversations. SHM has evolved to meet our growing needs, equipping hospitalists with tools to engage at every level, and most importantly, enabled us to find our common place.

Where do we go now? I suggest we continue to take the roads not taken and at the destination, build the map of tomorrow, together.

Dr. Siy is division medical director, hospital specialties, in the departments of hospital medicine and community senior and palliative care at HealthPartners in Bloomington, Minn. He is the new president of SHM.

Last month we converged virtually for our annual conference, SHM Converge – the second time since the start of the coronavirus pandemic. We are thankful for innovations and advancements in technology that have allowed the world, including SHM, to continue connecting us all together. And yet, 18 months in, having forged new roads, experienced unique and life-changing events, we long for the in-person human connection that allows us to share a common experience. At a time of imperatives in our world – a global pandemic, systemic racism, and deep geopolitical divides – more than ever, we need to converge. Isolation only festers, deepening our divisions and conflicts.

In high school, I read Robert Frost’s poem “The Road Not Taken” and clung to the notion of diverging roads and choosing the road less traveled. Like most young people, my years since reading the poem were filled with attempts at forging new paths and experiencing great things – and yet, always feeling unaccomplished. Was Oscar Wilde right when he wrote: “Life imitates Art far more than Art imitates Life?” After all, these past 18 months, we have shared in the traumas of our times, and still, we remain isolated and alone. Our diverse experiences have been real, both tragic and heroic, from east to west, city to country, black to white, and red to blue.

At SHM, it’s time to converge and face the great challenges of our lifetime. A deadly pandemic continues to rage around the world, bringing unprecedented human suffering and loss of lives. In its wake, this pandemic also laid bare the ugly face of systemic racism, brought our deepest divisions to the surface – all threatening the very fabric of our society. This pandemic has been a stress test for health care systems, revealing our vulnerabilities and expanding the chasm of care between urban and rural communities, all in turn worsening our growing health disparities. This moment needs convergence to rekindle connection and solidarity.

Scholars do not interpret “The Road Not Taken” as a recommendation to take the road less traveled. Instead, it is a suggestion that the diverging roads lead to a common place having been “worn about the same” as they “equally lay.” It is true that our roads are unique and shape our lives, but so, too, does the destination and common place our roads lead us to. At that common place, during these taxing times, SHM enables hospitalists to tackle these great challenges.

For over 2 decades of dynamic changes in health care, SHM has been the workshop where hospitalists converged to sharpen clinical skills, improve quality and safety, develop acute care models inside and outside of hospitals, advocate for better health policy and blaze new trails. Though the issues evolved, and new ones emerge, today is no different.

Indeed, this is an historic time. This weighted moment meets us at the crossroads. A moment that demands synergy, cooperation, and creativity. A dynamic change to health care policy, advances in care innovation, renewed prioritization of public health, and rich national discourse on our social fabric; hospitalists are essential to every one of those conversations. SHM has evolved to meet our growing needs, equipping hospitalists with tools to engage at every level, and most importantly, enabled us to find our common place.

Where do we go now? I suggest we continue to take the roads not taken and at the destination, build the map of tomorrow, together.

Dr. Siy is division medical director, hospital specialties, in the departments of hospital medicine and community senior and palliative care at HealthPartners in Bloomington, Minn. He is the new president of SHM.

Last month we converged virtually for our annual conference, SHM Converge – the second time since the start of the coronavirus pandemic. We are thankful for innovations and advancements in technology that have allowed the world, including SHM, to continue connecting us all together. And yet, 18 months in, having forged new roads, experienced unique and life-changing events, we long for the in-person human connection that allows us to share a common experience. At a time of imperatives in our world – a global pandemic, systemic racism, and deep geopolitical divides – more than ever, we need to converge. Isolation only festers, deepening our divisions and conflicts.

In high school, I read Robert Frost’s poem “The Road Not Taken” and clung to the notion of diverging roads and choosing the road less traveled. Like most young people, my years since reading the poem were filled with attempts at forging new paths and experiencing great things – and yet, always feeling unaccomplished. Was Oscar Wilde right when he wrote: “Life imitates Art far more than Art imitates Life?” After all, these past 18 months, we have shared in the traumas of our times, and still, we remain isolated and alone. Our diverse experiences have been real, both tragic and heroic, from east to west, city to country, black to white, and red to blue.

At SHM, it’s time to converge and face the great challenges of our lifetime. A deadly pandemic continues to rage around the world, bringing unprecedented human suffering and loss of lives. In its wake, this pandemic also laid bare the ugly face of systemic racism, brought our deepest divisions to the surface – all threatening the very fabric of our society. This pandemic has been a stress test for health care systems, revealing our vulnerabilities and expanding the chasm of care between urban and rural communities, all in turn worsening our growing health disparities. This moment needs convergence to rekindle connection and solidarity.

Scholars do not interpret “The Road Not Taken” as a recommendation to take the road less traveled. Instead, it is a suggestion that the diverging roads lead to a common place having been “worn about the same” as they “equally lay.” It is true that our roads are unique and shape our lives, but so, too, does the destination and common place our roads lead us to. At that common place, during these taxing times, SHM enables hospitalists to tackle these great challenges.

For over 2 decades of dynamic changes in health care, SHM has been the workshop where hospitalists converged to sharpen clinical skills, improve quality and safety, develop acute care models inside and outside of hospitals, advocate for better health policy and blaze new trails. Though the issues evolved, and new ones emerge, today is no different.

Indeed, this is an historic time. This weighted moment meets us at the crossroads. A moment that demands synergy, cooperation, and creativity. A dynamic change to health care policy, advances in care innovation, renewed prioritization of public health, and rich national discourse on our social fabric; hospitalists are essential to every one of those conversations. SHM has evolved to meet our growing needs, equipping hospitalists with tools to engage at every level, and most importantly, enabled us to find our common place.

Where do we go now? I suggest we continue to take the roads not taken and at the destination, build the map of tomorrow, together.

Dr. Siy is division medical director, hospital specialties, in the departments of hospital medicine and community senior and palliative care at HealthPartners in Bloomington, Minn. He is the new president of SHM.

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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

Quantitative assessment of the extent of interstitial lung disease in patients with systemic sclerosis and levels of certain proteins in bronchoalveolar lavage samples have potential for predicting mortality and disease progression, according to two analyses of data from the Scleroderma Lung Study I and II.

The analyses, presented at the annual European Congress of Rheumatology, aim to improve current prognostic abilities in patients with systemic sclerosis–interstitial lung disease (SSc-ILD). Although forced vital capacity is commonly used as a biomarker for survival in many SSc-ILD trials, other factors can affect FVC, such as respiratory muscle weakness and skin fibrosis. Further, FVC correlates poorly with patient-reported outcomes, explained first author Elizabeth Volkmann, MD, director of the scleroderma program at the University of California, Los Angeles, and the founder and codirector of the UCLA connective tissue disease–related interstitial lung disease program.

Dr. Volkmann presented two studies that investigated the potential of radiographic and protein biomarkers for predicting mortality and identifying patients at risk for ILD progression. The biomarkers may also help to identify patients who would benefit most from immunosuppressive therapy.

The first study found that tracking the quantitative extent of ILD (QILD) over time with high-resolution CT (HRCT) predicted poorer outcomes and could therefore act as a surrogate endpoint for mortality among patients with SSc-ILD. The other study identified associations between specific proteins from bronchoalveolar lavage (BAL) and the likelihood of ILD progression, although some associations were treatment dependent.

Jacob M. van Laar, MD, PhD, professor of rheumatology at the University Medical Center Utrecht (the Netherlands), who was not involved in the study, found the results intriguing and noted the importance of further validation in research before these biomarkers are considered for clinical use.

“It would be wonderful if we can tailor therapy based on BAL biomarkers in the future, as clinicians often struggle to decide on selection, timing, and duration of immunosuppressive treatment,” Dr. van Laar told this news organization. “This has become even more relevant with the introduction of new drugs such as nintedanib.”
 

Extent of ILD progression as a surrogate for mortality

Scleroderma Lung Study I involved 158 patients with SSc-ILD who were randomly assigned to receive either cyclophosphamide or placebo for 12 months. Scleroderma Lung Study II included 142 patients with SSc-ILD who were randomly assigned to receive either mycophenolate for 24 months or cyclophosphamide for 12 months followed by placebo for 12 months.

The researchers calculated QILD in the whole lung at baseline, at 12 months in the first trial, and at 24 months in the second trial. However, only 82 participants from the first trial and 90 participants from the second trial underwent HRCT. Demographic and disease characteristics were similar between the two groups on follow-up scans.

Follow-up continued for 12 years for patients in the first trial and 8 years in the second. The researchers compared survival rates between the 41% of participants from the first study and 31% of participants from the second study who had poorer QILD scores (at least a 2% increase) with the participants who had stable or improved scores (less than 2% increase).

Participants from both trials had significantly poorer long-term survival if their QILD scores had increased by at least 2% at follow-up (P = .01 for I; P = .019 for II). The association was no longer significant after adjustment for baseline FVC, age, and modified Rodnan skin score in the first trial (hazard ratio, 1.98; P = .089), but it remained significant for participants of the second trial (HR, 3.86; P = .014).

“Data from two independent trial cohorts demonstrated that radiographic progression of SSc-ILD at 1 and 2 years is associated with worse long-term survival,” Dr. Volkmann told attendees.

However, FVC did not significantly predict risk of mortality in either trial.

“To me, the most striking finding from the first study was that change in QILD performed better as a predictor of survival than change in FVC,” Dr. van Laar said in an interview. “This indicates QILD is fit for purpose and worth including in future clinical trials.”

Limitations of the study included lack of HRCT for all participants in the trials and the difference in timing (1 year and 2 years) of HRCT assessment between the two trials. The greater hazard ratio for worsened QILD in the second trial may suggest that assessment at 2 years provides more reliable data as a biomarker, Dr. Volkmann said.

“QILD may represent a better proxy for how a patient feels, functions, and survives than FVC,” she said.
 

Treatment-dependent biomarkers for worsening lung fibrosis

In the second study, the researchers looked for any associations between changes in the radiographic extent of SSc-ILD and 68 proteins from BAL.

“Being able to risk-stratify patients with interstitial lung disease at the time of diagnosis and predict which patients are likely to have a stable versus progressive disease course is critical for making important treatment decisions for these patients,” Dr. Volkmann told attendees.

The second study she presented involved Scleroderma Lung Study I. Of the 158 participants, 144 underwent a bronchoscopy, yielding BAL protein samples from 103 participants. The researchers determined the extent of radiographic fibrosis in the whole lung with quantitative imaging analysis of HRCT of the chest at baseline and 12 months.

Although the researchers identified several statistically significant associations between certain proteins and changes in radiographic fibrosis, “baseline protein levels were differentially associated with the course of ILD based on treatment status,” she told attendees.

For example, increased levels of the following proteins were linked to poor radiographic fibrosis scores for patients who received placebo:

• Granulocyte-macrophage colony-stimulating factor
• Interleukin-1
• Monocyte chemoattractant protein–3
• Chemokine ligand–5
• Transforming growth factor–beta
• Hepatocyte growth factor
• Stem cell factor
• IL-4
• TGF-alpha

Yet increases in these proteins predicted improvement in radiographic fibrosis in patients who had taken cyclophosphamide.

Independently of treatment, the researchers also identified an association between higher levels of fractalkine and poorer radiographic fibrosis scores and between higher IL-7 levels and improved radiographic fibrosis scores.

After adjusting for treatment arm and baseline severity of ILD, significant associations remained between change in radiographic fibrosis score and IL-1, MCP-3, surfactant protein C, IL-7 and CCL-5 levels.

“Biomarker discovery is really central to our ability to risk stratify patients with SSc-ILD,” Dr. Volkmann told attendees. “Understanding how biomarkers predict outcomes in treated and untreated patients may improve personalized medicine to patients with SSc-ILD and could also reveal novel treatment targets.”

Dr. van Laar said in an interview that this study’s biggest strength lay in its large sample size and in the comprehensiveness of the biomarkers studied.

“The findings are interesting from a research perspective and potentially relevant for clinical practice, but the utility of measuring biomarkers in BAL should be further studied for predictive value on clinical endpoints,” Dr. van Laar said. “BAL is an invasive procedure [that] is not routinely done.”

The research was funded by the National Institutes of Health. Dr. Volkmann has consulted for Boehringer Ingelheim and received grant funding from Corbus, Forbius, and Kadmon. Dr. van Laar has received grant funding or personal fees from Arthrogen, Arxx Therapeutics, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Gesynta, Leadiant, Merck Sharp & Dohme, Roche, Sanofi, and Thermofisher.

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