The global COVID-19 pandemic has escalated everyone’s stress levels, especially clinicians caring for hospitalized patients. New pressures have added to everyday stress, new studies have revised prior patient care recommendations, and the world generally seems upside down. What can a busy hospitalist do to maintain a modicum of sanity in all the craziness?

The stressors facing hospitalists

Uncertainty

Of all the burdens COVID-19 has unleashed, the biggest may be uncertainty. Not only is there unease about the virus itself, there also is legitimate concern about the future of medicine, said Elizabeth Harry, MD, SFHM, a hospitalist and senior director of clinical affairs at the University of Colorado Hospital in Aurora.

“What does it look like after an event like this, particularly in areas like academic medicine and teaching our next generation and getting funding for research? And how do we continue to produce physicians that can provide excellent care?” she asked.

There is also uncertainty in the best way to care for patients, said Eileen Barrett, MD, MPH, SFHM, a hospitalist at the University of New Mexico, Albuquerque.

“There are some models that are emerging to predict who will have a worse outcome, but they’re still not great models, so we have uncertainty for a given patient.” And, she noted, as the science continues to evolve, there exists a constant worry that “you might have inadvertently caused someone harm.”

The financial implications of the pandemic are creating uncertainty too. “When you fund a health care system with elective procedures and you can’t do those, and instead have to shift to the most essential services, a lot of places are seeing a massive deficit, which is going to affect staff morale and some physician offices are going to close,” said Elisabeth Poorman, MD, MPH, a primary care and internal medicine physician and chair of the King County Medical Society Physician Wellness Committee in Seattle.
 

Fear

When the pandemic began in the United States, “fear of the unknown was perhaps the scariest part, particularly as it pertained to personal protective equipment,” said Mark Rudolph, MD, SFHM, chief experience officer and vice president of patient experience and physician development at Sound Physicians in Tacoma, Wash. “For most clinicians, this is the first time that they are themselves in harm’s way while they do their jobs. And worse, they risk bringing the virus home to their families. That is the concern I hear most.”

Anxiety

Worrying about being able to provide excellent patient care is a big stressor, especially since this is the heart and soul of why most hospitalists have gone into their line of work.

“Part of providing excellent care to your patients is providing excellent supportive care to their families,” Dr. Harry said. “There’s some dissonance there in not being able to allow the family to come visit, but wanting to keep them safe, and it feels really hard to support your patients and support their families in the best way. It can feel like you’re just watching and waiting to see what will happen, and that we don’t have a lot of agency over which direction things take.”

There is concern for health care team members as well, Dr. Harry added. “Physicians care a lot about their teams and how they’re doing. I think there’s a sense of esprit de corps among folks and worry for each other there.”
 

Guilt

Although you may be at the hospital all day, you may feel guilty when you are not providing direct patient care. Or maybe you or someone on your team has an immunodeficiency and can’t be on the front line. Perhaps one of your team members contracted COVID-19 and you did not. Whatever the case, guilt is another emotion that is rampant among hospitalists right now, Dr. Barrett said.

Burnout

Unfortunately, burnout is a potential reality in times of high stress. “Burnout is dynamic,” said Dr. Poorman. “It’s a process by which your emotional and cognitive reserves are exhausted. The people with the highest burnout are the ones who are still trying to provide the standard of care, or above the standard of care in dysfunctional systems.”

Dr. Harry noted that burnout presents in different ways for different people, but Dr. Rudolph added that it’s crucial for hospitalist team members to watch for signs of burnout so they can intervene and/or get help for their colleagues.

Warning signs in yourself or others that burnout could be on the horizon include:

• Fatigue/exhaustion – Whether emotional or physical (or both), this can become a problem if it “just doesn’t seem to go away despite rest and time away from work,” said Dr. Rudolph.
• Behavioral changes – Any behavior that’s out of the ordinary may be a red flag, like lashing out at someone at work.
• Overwork – Working too much can be caused by an inability to let go of patient care, Dr. Barrett said.
• Not working enough – This may include avoiding tasks and having difficulty meeting deadlines.
• Maladaptive coping behaviors – Excessive consumption of alcohol or drugs is a common coping mechanism. “Even excessive consumption of news is something that people are using to numb out a little bit,” said Dr. Harry.
• Depersonalization – “This is where you start to look at patients, colleagues, or administrators as ‘them’ and you can’t connect as deeply,” Dr. Harry said. “Part of that’s protective and a normal thing to do during a big trauma like this, but it’s also incredibly distancing. Any language that people start using that feels like ‘us’ or ‘them’ is a warning sign.”
• Disengagement – Many people disengage from their work, but Dr. Poorman said physicians tend to disengage from other parts of their lives, such as exercise and family interaction.

Protecting yourself while supporting others

Like the illustration of putting the oxygen mask on yourself first so you can help others, it’s important to protect your own mental and physical health as you support your fellow physicians. Here’s what the experts suggest.

Focus on basic needs

“When you’re in the midst of a trauma, which we are, you don’t want to open all of that up and go to the depths of your thoughts about the grief of all of it because it can actually make the trauma worse,” said Dr. Harry. “There’s a lot of literature that debriefing is really helpful after the event, but if you do it during the event, it can be really dangerous.”

Instead, she said, the goal should be focusing on your basic needs and what you need to do to get through each day, like keeping you and your family in good health. “What is your purpose? Staying connected to why you do this and staying focused on the present is really important,” Dr. Harry noted.

Do your best to get a good night’s sleep, exercise as much as you can, talk to others, and see a mental health provider if your anxiety is too high, advises Dr. Barrett. “Even avoiding blue light from phones and screens within 2 hours of bedtime, parking further away from the hospital and walking, and taking the stairs are things that add up in a big way.”
 

Keep up your normal routine

“Right now, it’s really critical for clinicians to keep up components of their routine that feel ‘normal,’ ” Dr. Rudolph said. “Whether it’s exercise, playing board games with their kids, or spending time on a hobby, it’s critical to allow yourself these comfortable, predictable, and rewarding detours.”

Set limits

People under stress tend to find unhealthy ways to cope. Instead, try being intentional about what you are consuming by putting limits on things like your news, alcohol consumption, and the number of hours you work, said Dr. Harry.

Implement a culture of wellness

Dr. Barrett believes in creating the work culture we want to be in, one that ensures people have psychological safety, allows them to ask for help, encourages them to disconnect completely from work, and makes them feel valued and listened to. She likes the example of “the pause,” which is called by a team member right after a patient expires.

“It’s a 30-second moment of silence where we reflect on the patient, their loved ones, and every member of the health care team who helped support and treat them,” said Dr. Barrett. “At the conclusion, you say: ‘Thank you. Is there anything you need to be able to go back to the care of other patients?’ Because it’s unnatural to have this terrible thing that happened and then just act like nothing happened.”
 

Target resources

Be proactive and know where to find resources before you need them, advised Dr. Harry. “Most institutions have free mental health resources, either through their employee assistance programs or HR, plus there’s lots of national organizations that are offering free resources to health care providers.”

Focus on what you can control

Separating what is under your control from what is not is a struggle for everyone, Dr. Poorman said, but it’s helpful to think about the ways you can have an impact and what you’re able to control.

“There was a woman who was diagnosed with early-onset Parkinson’s that I heard giving an interview at the beginning of this pandemic,” she said. “It was the most helpful advice I got, which was: ‘Think of the next good thing you can do.’ You can’t fix everything, so what’s the next good thing you can do?”
 

Maintain connectivity

Make sure you are utilizing your support circle and staying connected. “That sense of connection is incredibly protective on multiple fronts for depression, for burnout, for suicide ideation, etc.,” Dr. Harry said.

“It doesn’t matter if it’s your teammates at work, your family at home, your best friend from medical school – whomever you can debrief with, vent with, and just share your thoughts and feelings with, these outlets are critical for all of us to process our emotions and diffuse stress and anxiety,” said Dr. Rudolph.

Dr. Poorman is concerned that there could be a spike in physician suicides caused by increased stress, so she also encourages talking openly about what is going on and about getting help when it’s necessary. “Many of us are afraid to seek care because we can actually have our ability to practice medicine questioned, but now is not the time for heroes. Now is the time for people who are willing to recognize their own strengths and limitations to take care of one another.”
 

Be compassionate toward others

Keep in mind that everyone is stressed out and offer empathy and compassion. “I think everybody’s struggling to try to figure this out and the more that we can give each other the benefit of the doubt and a little grace, the more protective that is,” said Dr. Harry.

Listening is meaningful too. “Recognizing opportunities to validate and acknowledge the feelings that are being shared with you by your colleagues is critical,” Dr. Rudolph said. “We all need to know that we’re not alone, that our thoughts and feelings are okay, and when we share a difficult story, the value of someone saying something as simple as, ‘wow, that sounds like it was really hard,’ is immense.”
 

Be compassionate toward yourself

Try to give yourself a break and be as compassionate with yourself as you would with others. It’s okay that you’re not getting in shape, publishing prolifically, or redesigning your house right now.

“There’s a lot of data linking lack of self-compassion to burnout,” said Dr. Harry. She says there are courses on self-compassion available that help you work on being kinder to yourself.
 

Get a “battle buddy”

The American Medical Association has a free “buddy system” program called PeerRx to help physicians cope during the pandemic. Dr. Rudolph said that now is a great time to use this military-developed intervention in which each team member checks in with a chosen partner at agreed-upon intervals.

For example, “You can tell that person: ‘If I don’t call my family for a week that’s a red flag for me.’ And then you hold each other accountable to those things,” Dr. Harry said.

The buddy system is another way to harness that sense of connection that is so vital to our health and well-being.

“The simple act of showing that you care … can make all the difference when you’re doing this kind of work that is both challenging and dangerous,” said Dr. Rudolph.

The global COVID-19 pandemic has escalated everyone’s stress levels, especially clinicians caring for hospitalized patients. New pressures have added to everyday stress, new studies have revised prior patient care recommendations, and the world generally seems upside down. What can a busy hospitalist do to maintain a modicum of sanity in all the craziness?

The stressors facing hospitalists

Uncertainty

Of all the burdens COVID-19 has unleashed, the biggest may be uncertainty. Not only is there unease about the virus itself, there also is legitimate concern about the future of medicine, said Elizabeth Harry, MD, SFHM, a hospitalist and senior director of clinical affairs at the University of Colorado Hospital in Aurora.

“What does it look like after an event like this, particularly in areas like academic medicine and teaching our next generation and getting funding for research? And how do we continue to produce physicians that can provide excellent care?” she asked.

There is also uncertainty in the best way to care for patients, said Eileen Barrett, MD, MPH, SFHM, a hospitalist at the University of New Mexico, Albuquerque.

“There are some models that are emerging to predict who will have a worse outcome, but they’re still not great models, so we have uncertainty for a given patient.” And, she noted, as the science continues to evolve, there exists a constant worry that “you might have inadvertently caused someone harm.”

The financial implications of the pandemic are creating uncertainty too. “When you fund a health care system with elective procedures and you can’t do those, and instead have to shift to the most essential services, a lot of places are seeing a massive deficit, which is going to affect staff morale and some physician offices are going to close,” said Elisabeth Poorman, MD, MPH, a primary care and internal medicine physician and chair of the King County Medical Society Physician Wellness Committee in Seattle.
 

Fear

When the pandemic began in the United States, “fear of the unknown was perhaps the scariest part, particularly as it pertained to personal protective equipment,” said Mark Rudolph, MD, SFHM, chief experience officer and vice president of patient experience and physician development at Sound Physicians in Tacoma, Wash. “For most clinicians, this is the first time that they are themselves in harm’s way while they do their jobs. And worse, they risk bringing the virus home to their families. That is the concern I hear most.”

Anxiety

Worrying about being able to provide excellent patient care is a big stressor, especially since this is the heart and soul of why most hospitalists have gone into their line of work.

“Part of providing excellent care to your patients is providing excellent supportive care to their families,” Dr. Harry said. “There’s some dissonance there in not being able to allow the family to come visit, but wanting to keep them safe, and it feels really hard to support your patients and support their families in the best way. It can feel like you’re just watching and waiting to see what will happen, and that we don’t have a lot of agency over which direction things take.”

There is concern for health care team members as well, Dr. Harry added. “Physicians care a lot about their teams and how they’re doing. I think there’s a sense of esprit de corps among folks and worry for each other there.”
 

Guilt

Although you may be at the hospital all day, you may feel guilty when you are not providing direct patient care. Or maybe you or someone on your team has an immunodeficiency and can’t be on the front line. Perhaps one of your team members contracted COVID-19 and you did not. Whatever the case, guilt is another emotion that is rampant among hospitalists right now, Dr. Barrett said.

Burnout

Unfortunately, burnout is a potential reality in times of high stress. “Burnout is dynamic,” said Dr. Poorman. “It’s a process by which your emotional and cognitive reserves are exhausted. The people with the highest burnout are the ones who are still trying to provide the standard of care, or above the standard of care in dysfunctional systems.”

Dr. Harry noted that burnout presents in different ways for different people, but Dr. Rudolph added that it’s crucial for hospitalist team members to watch for signs of burnout so they can intervene and/or get help for their colleagues.

Warning signs in yourself or others that burnout could be on the horizon include:

• Fatigue/exhaustion – Whether emotional or physical (or both), this can become a problem if it “just doesn’t seem to go away despite rest and time away from work,” said Dr. Rudolph.
• Behavioral changes – Any behavior that’s out of the ordinary may be a red flag, like lashing out at someone at work.
• Overwork – Working too much can be caused by an inability to let go of patient care, Dr. Barrett said.
• Not working enough – This may include avoiding tasks and having difficulty meeting deadlines.
• Maladaptive coping behaviors – Excessive consumption of alcohol or drugs is a common coping mechanism. “Even excessive consumption of news is something that people are using to numb out a little bit,” said Dr. Harry.
• Depersonalization – “This is where you start to look at patients, colleagues, or administrators as ‘them’ and you can’t connect as deeply,” Dr. Harry said. “Part of that’s protective and a normal thing to do during a big trauma like this, but it’s also incredibly distancing. Any language that people start using that feels like ‘us’ or ‘them’ is a warning sign.”
• Disengagement – Many people disengage from their work, but Dr. Poorman said physicians tend to disengage from other parts of their lives, such as exercise and family interaction.

Protecting yourself while supporting others

Like the illustration of putting the oxygen mask on yourself first so you can help others, it’s important to protect your own mental and physical health as you support your fellow physicians. Here’s what the experts suggest.

Focus on basic needs

“When you’re in the midst of a trauma, which we are, you don’t want to open all of that up and go to the depths of your thoughts about the grief of all of it because it can actually make the trauma worse,” said Dr. Harry. “There’s a lot of literature that debriefing is really helpful after the event, but if you do it during the event, it can be really dangerous.”

Instead, she said, the goal should be focusing on your basic needs and what you need to do to get through each day, like keeping you and your family in good health. “What is your purpose? Staying connected to why you do this and staying focused on the present is really important,” Dr. Harry noted.

Do your best to get a good night’s sleep, exercise as much as you can, talk to others, and see a mental health provider if your anxiety is too high, advises Dr. Barrett. “Even avoiding blue light from phones and screens within 2 hours of bedtime, parking further away from the hospital and walking, and taking the stairs are things that add up in a big way.”
 

Keep up your normal routine

“Right now, it’s really critical for clinicians to keep up components of their routine that feel ‘normal,’ ” Dr. Rudolph said. “Whether it’s exercise, playing board games with their kids, or spending time on a hobby, it’s critical to allow yourself these comfortable, predictable, and rewarding detours.”

Set limits

People under stress tend to find unhealthy ways to cope. Instead, try being intentional about what you are consuming by putting limits on things like your news, alcohol consumption, and the number of hours you work, said Dr. Harry.

Implement a culture of wellness

Dr. Barrett believes in creating the work culture we want to be in, one that ensures people have psychological safety, allows them to ask for help, encourages them to disconnect completely from work, and makes them feel valued and listened to. She likes the example of “the pause,” which is called by a team member right after a patient expires.

“It’s a 30-second moment of silence where we reflect on the patient, their loved ones, and every member of the health care team who helped support and treat them,” said Dr. Barrett. “At the conclusion, you say: ‘Thank you. Is there anything you need to be able to go back to the care of other patients?’ Because it’s unnatural to have this terrible thing that happened and then just act like nothing happened.”
 

Target resources

Be proactive and know where to find resources before you need them, advised Dr. Harry. “Most institutions have free mental health resources, either through their employee assistance programs or HR, plus there’s lots of national organizations that are offering free resources to health care providers.”

Focus on what you can control

Separating what is under your control from what is not is a struggle for everyone, Dr. Poorman said, but it’s helpful to think about the ways you can have an impact and what you’re able to control.

“There was a woman who was diagnosed with early-onset Parkinson’s that I heard giving an interview at the beginning of this pandemic,” she said. “It was the most helpful advice I got, which was: ‘Think of the next good thing you can do.’ You can’t fix everything, so what’s the next good thing you can do?”
 

Maintain connectivity

Make sure you are utilizing your support circle and staying connected. “That sense of connection is incredibly protective on multiple fronts for depression, for burnout, for suicide ideation, etc.,” Dr. Harry said.

“It doesn’t matter if it’s your teammates at work, your family at home, your best friend from medical school – whomever you can debrief with, vent with, and just share your thoughts and feelings with, these outlets are critical for all of us to process our emotions and diffuse stress and anxiety,” said Dr. Rudolph.

Dr. Poorman is concerned that there could be a spike in physician suicides caused by increased stress, so she also encourages talking openly about what is going on and about getting help when it’s necessary. “Many of us are afraid to seek care because we can actually have our ability to practice medicine questioned, but now is not the time for heroes. Now is the time for people who are willing to recognize their own strengths and limitations to take care of one another.”
 

Be compassionate toward others

Keep in mind that everyone is stressed out and offer empathy and compassion. “I think everybody’s struggling to try to figure this out and the more that we can give each other the benefit of the doubt and a little grace, the more protective that is,” said Dr. Harry.

Listening is meaningful too. “Recognizing opportunities to validate and acknowledge the feelings that are being shared with you by your colleagues is critical,” Dr. Rudolph said. “We all need to know that we’re not alone, that our thoughts and feelings are okay, and when we share a difficult story, the value of someone saying something as simple as, ‘wow, that sounds like it was really hard,’ is immense.”
 

Be compassionate toward yourself

Try to give yourself a break and be as compassionate with yourself as you would with others. It’s okay that you’re not getting in shape, publishing prolifically, or redesigning your house right now.

“There’s a lot of data linking lack of self-compassion to burnout,” said Dr. Harry. She says there are courses on self-compassion available that help you work on being kinder to yourself.
 

Get a “battle buddy”

The American Medical Association has a free “buddy system” program called PeerRx to help physicians cope during the pandemic. Dr. Rudolph said that now is a great time to use this military-developed intervention in which each team member checks in with a chosen partner at agreed-upon intervals.

For example, “You can tell that person: ‘If I don’t call my family for a week that’s a red flag for me.’ And then you hold each other accountable to those things,” Dr. Harry said.

The buddy system is another way to harness that sense of connection that is so vital to our health and well-being.

“The simple act of showing that you care … can make all the difference when you’re doing this kind of work that is both challenging and dangerous,” said Dr. Rudolph.

The global COVID-19 pandemic has escalated everyone’s stress levels, especially clinicians caring for hospitalized patients. New pressures have added to everyday stress, new studies have revised prior patient care recommendations, and the world generally seems upside down. What can a busy hospitalist do to maintain a modicum of sanity in all the craziness?

The stressors facing hospitalists

Uncertainty

Of all the burdens COVID-19 has unleashed, the biggest may be uncertainty. Not only is there unease about the virus itself, there also is legitimate concern about the future of medicine, said Elizabeth Harry, MD, SFHM, a hospitalist and senior director of clinical affairs at the University of Colorado Hospital in Aurora.

“What does it look like after an event like this, particularly in areas like academic medicine and teaching our next generation and getting funding for research? And how do we continue to produce physicians that can provide excellent care?” she asked.

There is also uncertainty in the best way to care for patients, said Eileen Barrett, MD, MPH, SFHM, a hospitalist at the University of New Mexico, Albuquerque.

“There are some models that are emerging to predict who will have a worse outcome, but they’re still not great models, so we have uncertainty for a given patient.” And, she noted, as the science continues to evolve, there exists a constant worry that “you might have inadvertently caused someone harm.”

The financial implications of the pandemic are creating uncertainty too. “When you fund a health care system with elective procedures and you can’t do those, and instead have to shift to the most essential services, a lot of places are seeing a massive deficit, which is going to affect staff morale and some physician offices are going to close,” said Elisabeth Poorman, MD, MPH, a primary care and internal medicine physician and chair of the King County Medical Society Physician Wellness Committee in Seattle.
 

Fear

When the pandemic began in the United States, “fear of the unknown was perhaps the scariest part, particularly as it pertained to personal protective equipment,” said Mark Rudolph, MD, SFHM, chief experience officer and vice president of patient experience and physician development at Sound Physicians in Tacoma, Wash. “For most clinicians, this is the first time that they are themselves in harm’s way while they do their jobs. And worse, they risk bringing the virus home to their families. That is the concern I hear most.”

Anxiety

Worrying about being able to provide excellent patient care is a big stressor, especially since this is the heart and soul of why most hospitalists have gone into their line of work.

“Part of providing excellent care to your patients is providing excellent supportive care to their families,” Dr. Harry said. “There’s some dissonance there in not being able to allow the family to come visit, but wanting to keep them safe, and it feels really hard to support your patients and support their families in the best way. It can feel like you’re just watching and waiting to see what will happen, and that we don’t have a lot of agency over which direction things take.”

There is concern for health care team members as well, Dr. Harry added. “Physicians care a lot about their teams and how they’re doing. I think there’s a sense of esprit de corps among folks and worry for each other there.”
 

Guilt

Although you may be at the hospital all day, you may feel guilty when you are not providing direct patient care. Or maybe you or someone on your team has an immunodeficiency and can’t be on the front line. Perhaps one of your team members contracted COVID-19 and you did not. Whatever the case, guilt is another emotion that is rampant among hospitalists right now, Dr. Barrett said.

Burnout

Unfortunately, burnout is a potential reality in times of high stress. “Burnout is dynamic,” said Dr. Poorman. “It’s a process by which your emotional and cognitive reserves are exhausted. The people with the highest burnout are the ones who are still trying to provide the standard of care, or above the standard of care in dysfunctional systems.”

Dr. Harry noted that burnout presents in different ways for different people, but Dr. Rudolph added that it’s crucial for hospitalist team members to watch for signs of burnout so they can intervene and/or get help for their colleagues.

Warning signs in yourself or others that burnout could be on the horizon include:

• Fatigue/exhaustion – Whether emotional or physical (or both), this can become a problem if it “just doesn’t seem to go away despite rest and time away from work,” said Dr. Rudolph.
• Behavioral changes – Any behavior that’s out of the ordinary may be a red flag, like lashing out at someone at work.
• Overwork – Working too much can be caused by an inability to let go of patient care, Dr. Barrett said.
• Not working enough – This may include avoiding tasks and having difficulty meeting deadlines.
• Maladaptive coping behaviors – Excessive consumption of alcohol or drugs is a common coping mechanism. “Even excessive consumption of news is something that people are using to numb out a little bit,” said Dr. Harry.
• Depersonalization – “This is where you start to look at patients, colleagues, or administrators as ‘them’ and you can’t connect as deeply,” Dr. Harry said. “Part of that’s protective and a normal thing to do during a big trauma like this, but it’s also incredibly distancing. Any language that people start using that feels like ‘us’ or ‘them’ is a warning sign.”
• Disengagement – Many people disengage from their work, but Dr. Poorman said physicians tend to disengage from other parts of their lives, such as exercise and family interaction.

Protecting yourself while supporting others

Like the illustration of putting the oxygen mask on yourself first so you can help others, it’s important to protect your own mental and physical health as you support your fellow physicians. Here’s what the experts suggest.

Focus on basic needs

“When you’re in the midst of a trauma, which we are, you don’t want to open all of that up and go to the depths of your thoughts about the grief of all of it because it can actually make the trauma worse,” said Dr. Harry. “There’s a lot of literature that debriefing is really helpful after the event, but if you do it during the event, it can be really dangerous.”

Instead, she said, the goal should be focusing on your basic needs and what you need to do to get through each day, like keeping you and your family in good health. “What is your purpose? Staying connected to why you do this and staying focused on the present is really important,” Dr. Harry noted.

Do your best to get a good night’s sleep, exercise as much as you can, talk to others, and see a mental health provider if your anxiety is too high, advises Dr. Barrett. “Even avoiding blue light from phones and screens within 2 hours of bedtime, parking further away from the hospital and walking, and taking the stairs are things that add up in a big way.”
 

Keep up your normal routine

“Right now, it’s really critical for clinicians to keep up components of their routine that feel ‘normal,’ ” Dr. Rudolph said. “Whether it’s exercise, playing board games with their kids, or spending time on a hobby, it’s critical to allow yourself these comfortable, predictable, and rewarding detours.”

Set limits

People under stress tend to find unhealthy ways to cope. Instead, try being intentional about what you are consuming by putting limits on things like your news, alcohol consumption, and the number of hours you work, said Dr. Harry.

Implement a culture of wellness

Dr. Barrett believes in creating the work culture we want to be in, one that ensures people have psychological safety, allows them to ask for help, encourages them to disconnect completely from work, and makes them feel valued and listened to. She likes the example of “the pause,” which is called by a team member right after a patient expires.

“It’s a 30-second moment of silence where we reflect on the patient, their loved ones, and every member of the health care team who helped support and treat them,” said Dr. Barrett. “At the conclusion, you say: ‘Thank you. Is there anything you need to be able to go back to the care of other patients?’ Because it’s unnatural to have this terrible thing that happened and then just act like nothing happened.”
 

Target resources

Be proactive and know where to find resources before you need them, advised Dr. Harry. “Most institutions have free mental health resources, either through their employee assistance programs or HR, plus there’s lots of national organizations that are offering free resources to health care providers.”

Focus on what you can control

Separating what is under your control from what is not is a struggle for everyone, Dr. Poorman said, but it’s helpful to think about the ways you can have an impact and what you’re able to control.

“There was a woman who was diagnosed with early-onset Parkinson’s that I heard giving an interview at the beginning of this pandemic,” she said. “It was the most helpful advice I got, which was: ‘Think of the next good thing you can do.’ You can’t fix everything, so what’s the next good thing you can do?”
 

Maintain connectivity

Make sure you are utilizing your support circle and staying connected. “That sense of connection is incredibly protective on multiple fronts for depression, for burnout, for suicide ideation, etc.,” Dr. Harry said.

“It doesn’t matter if it’s your teammates at work, your family at home, your best friend from medical school – whomever you can debrief with, vent with, and just share your thoughts and feelings with, these outlets are critical for all of us to process our emotions and diffuse stress and anxiety,” said Dr. Rudolph.

Dr. Poorman is concerned that there could be a spike in physician suicides caused by increased stress, so she also encourages talking openly about what is going on and about getting help when it’s necessary. “Many of us are afraid to seek care because we can actually have our ability to practice medicine questioned, but now is not the time for heroes. Now is the time for people who are willing to recognize their own strengths and limitations to take care of one another.”
 

Be compassionate toward others

Keep in mind that everyone is stressed out and offer empathy and compassion. “I think everybody’s struggling to try to figure this out and the more that we can give each other the benefit of the doubt and a little grace, the more protective that is,” said Dr. Harry.

Listening is meaningful too. “Recognizing opportunities to validate and acknowledge the feelings that are being shared with you by your colleagues is critical,” Dr. Rudolph said. “We all need to know that we’re not alone, that our thoughts and feelings are okay, and when we share a difficult story, the value of someone saying something as simple as, ‘wow, that sounds like it was really hard,’ is immense.”
 

Be compassionate toward yourself

Try to give yourself a break and be as compassionate with yourself as you would with others. It’s okay that you’re not getting in shape, publishing prolifically, or redesigning your house right now.

“There’s a lot of data linking lack of self-compassion to burnout,” said Dr. Harry. She says there are courses on self-compassion available that help you work on being kinder to yourself.
 

Get a “battle buddy”

The American Medical Association has a free “buddy system” program called PeerRx to help physicians cope during the pandemic. Dr. Rudolph said that now is a great time to use this military-developed intervention in which each team member checks in with a chosen partner at agreed-upon intervals.

For example, “You can tell that person: ‘If I don’t call my family for a week that’s a red flag for me.’ And then you hold each other accountable to those things,” Dr. Harry said.

The buddy system is another way to harness that sense of connection that is so vital to our health and well-being.

“The simple act of showing that you care … can make all the difference when you’re doing this kind of work that is both challenging and dangerous,” said Dr. Rudolph.

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

Can we help our pediatric patients with the complicated problems of racism, especially if we are privileged (and even white) professionals? We may not have experienced discrimination, but we can still advise and address it. Racist discrimination, fear, trauma, or distress may produce or exacerbate conditions we are treating. I have found it often revealing to ask: “Have you, your child, or your family had an experience with racism that may be contributing to today’s concern?”

Tverdokhlib/Shutterstock

Three levels of racism impact children’s health and health care: “structural or institutional” policies that influence social determinants of health; “personally mediated” differential treatment based on assumptions about one’s abilities, motives, or intents; and the resulting “internalization” of stereotypes into one’s identity, undermining confidence, self-esteem, and mental health. We can help advocate about structural racism and ensure equity within our offices, but how best to counsel the families and children themselves?

Racism includes actions of “assigning value based on the social interpretation of how a person looks” (Ethn Dis. 2008;18[4]:496-504). “Social interpretations” develop from an early age. Newborns detect differences in appearance and may startle or cry seeing a parent’s drastic haircut or new hat. Parents generally know to use soothing words and tone, bring the difference into view gradually, smile and comfort the child, and explain the change; these are good skills for later, too. Infants notice skin color, which, unlike clothes, is a stable feature by which to recognize parents. Social interpretation of these differences is cued from the parents’ feelings and reactions. Adults naturally transmit biases from their own past unless they work to dampen them. If the parent was taught to regard “other” as negative or is generally fearful, the child mirrors this. Working to reduce racism thus requires parents (and professionals) to examine their prejudices to be able to convey positive or neutral reactions to people who are different. Parents need to show curiosity, positive affect, and comfort about people who are different, and do well to seek contact and friendships with people from other groups and include their children in these relationships. We can encourage this outreach plus ensure diversity and respectful interactions in our offices.

Children from age 3 years value fairness and are upset seeing others treated unfairly – easily understanding “not fair” or “mean.” If the person being hurt is like them in race, ethnicity, religion, gender, or sexual preference, they also fear for themselves, family, and friends. Balance is needed in discussing racism to avoid increasing fear or overpromising as risks are real and solutions difficult. Children look to adults for understanding and evidence of action to feel safer, rather than helpless. We should state that leaders are working on “making the rules more fair,” ensuring that people “won’t be allowed do it again,” and “teaching that everyone deserves respect.” Even better, parents and children can generate ideas about child actions, giving them some power as an antidote to anxiety. Age-related possibilities might include drawing a picture of people getting along, talking at show-and-tell, writing a note to officials, making a protest sign, posting thoughts on Facebook, or protesting.

With age, the culture increasingly influences a child’s attitudes. Children see lots of teasing and bullying based on differences from being overweight or wearing glasses, to skin color. It is helpful to interpret for children that bullies are insecure, or sometimes have been hurt, and they put other people down to feel better than someone else. Thinking about racist acts this way may reduce the desire for revenge and a cycle of aggression. Effective anti-bullying programs help children recognize bullying, see it as an emergency that requires their action, tell adults, and take action. This action could be surrounding the bully, standing tall, making eye contact, having a dismissive retort, or asking questions that require the bully to think, such as “What do you want to happen by doing this?” We can coach our patients and their parents on these principles as well as advising schools.

Children need to be told that those being put down or held down – especially those like them – have strengths; have made discoveries; have produced writings, art, and music; have shown military bravery, moral leadership, and resistance to discrimination, but it is not the time to show strength when confronted by a gun or police. We can use and arm parents with examples to discuss strengths and accomplishments to help buffer the child from internalization of racist stereotypes. Children need positive role models who look like them; parents can seek out diverse professionals in their children’s lives, such as dentists, doctors, teachers, clergy, mentors, or coaches. We, and parents, can ensure that dolls and books are available, and that the children’s shows, movies, and video games are watched together and include diverse people doing good or brave things. These exposures also are key to all children becoming anti-racist.

Parents can be advised to initiate discussion of racism because children, detecting adult discomfort, may avoid the topic. We can encourage families to give their point of view; otherwise children simply absorb those of peers or the press. Parents should tell their children, “I want you to be able to talk about it if someone is mean or treats you unfairly because of [the color of your skin, your religion, your sex, your disability, etc.]. You might feel helpless, or angry, which is natural. We need to talk about this so you can feel strong. Then we can plan on what we are going to do.” The “sandwich” method of “ask-give information-ask what they think” can encourage discussion and correct misperceptions.

Racist policies have succeeded partly by adult “bullies” dehumanizing the “other.” Most children can consider someone else’s point of view by 4½ years old, shaped with adult help. Parents can begin by telling babies, “That hurts, doesn’t it?” asking toddlers and older, “How would you feel if ... [someone called you a name just because of having red hair]?” or “How do you think she feels when ... [someone pushes her out of line because she wears certain clothes]?” in cases of grabbing, not sharing, hitting, bullying, etc. Older children and teens can analyze more abstract situations when asked, “What if you were the one who ... [got expelled for mumbling about the teacher]?” or “What if that were your sister?” or “How would the world be if everyone ... [got a chance to go to college]?” We can encourage parents to propose these mental exercises to build the child’s perspective-taking while conveying their opinions.

Experiences, including through media, may increase or decrease fear; the child needs to have a supportive person moderating the exposure, providing a positive interpretation, and protecting the child from overwhelm, if needed.

Experiences are insufficient for developing anti-racist attitudes; listening and talking are needed. The first step is to ask children about what they notice, think, and feel about situations reflecting racism, especially as they lack words for these complicated observations. There are television, Internet, and newspaper examples of both racism and anti-racism that can be fruitfully discussed. We can recommend watching or reading together, and asking questions such as, “Why do you think they are shouting [protesting]?” “How do you think the [victim, police] felt?” or “What do you think should be done about this?”

It is important to acknowledge the child’s confusion, fear, anxiety, sadness, or anger as normal and appropriate, not dismissing, too quickly reassuring, or changing the subject, even though it’s uncomfortable.

Physicians and nurse practitioners can make a difference by being aware of our privilege and biases, being open, modeling discussion, screening for impact, offering strategies, advocating with schools, and providing resources such as therapy or legal counsel, as for other social determinants of health.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (https://www.site.chadis.com/). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at pdnews@mdedge.com.

Can we help our pediatric patients with the complicated problems of racism, especially if we are privileged (and even white) professionals? We may not have experienced discrimination, but we can still advise and address it. Racist discrimination, fear, trauma, or distress may produce or exacerbate conditions we are treating. I have found it often revealing to ask: “Have you, your child, or your family had an experience with racism that may be contributing to today’s concern?”

Tverdokhlib/Shutterstock

Three levels of racism impact children’s health and health care: “structural or institutional” policies that influence social determinants of health; “personally mediated” differential treatment based on assumptions about one’s abilities, motives, or intents; and the resulting “internalization” of stereotypes into one’s identity, undermining confidence, self-esteem, and mental health. We can help advocate about structural racism and ensure equity within our offices, but how best to counsel the families and children themselves?

Racism includes actions of “assigning value based on the social interpretation of how a person looks” (Ethn Dis. 2008;18[4]:496-504). “Social interpretations” develop from an early age. Newborns detect differences in appearance and may startle or cry seeing a parent’s drastic haircut or new hat. Parents generally know to use soothing words and tone, bring the difference into view gradually, smile and comfort the child, and explain the change; these are good skills for later, too. Infants notice skin color, which, unlike clothes, is a stable feature by which to recognize parents. Social interpretation of these differences is cued from the parents’ feelings and reactions. Adults naturally transmit biases from their own past unless they work to dampen them. If the parent was taught to regard “other” as negative or is generally fearful, the child mirrors this. Working to reduce racism thus requires parents (and professionals) to examine their prejudices to be able to convey positive or neutral reactions to people who are different. Parents need to show curiosity, positive affect, and comfort about people who are different, and do well to seek contact and friendships with people from other groups and include their children in these relationships. We can encourage this outreach plus ensure diversity and respectful interactions in our offices.

Children from age 3 years value fairness and are upset seeing others treated unfairly – easily understanding “not fair” or “mean.” If the person being hurt is like them in race, ethnicity, religion, gender, or sexual preference, they also fear for themselves, family, and friends. Balance is needed in discussing racism to avoid increasing fear or overpromising as risks are real and solutions difficult. Children look to adults for understanding and evidence of action to feel safer, rather than helpless. We should state that leaders are working on “making the rules more fair,” ensuring that people “won’t be allowed do it again,” and “teaching that everyone deserves respect.” Even better, parents and children can generate ideas about child actions, giving them some power as an antidote to anxiety. Age-related possibilities might include drawing a picture of people getting along, talking at show-and-tell, writing a note to officials, making a protest sign, posting thoughts on Facebook, or protesting.

With age, the culture increasingly influences a child’s attitudes. Children see lots of teasing and bullying based on differences from being overweight or wearing glasses, to skin color. It is helpful to interpret for children that bullies are insecure, or sometimes have been hurt, and they put other people down to feel better than someone else. Thinking about racist acts this way may reduce the desire for revenge and a cycle of aggression. Effective anti-bullying programs help children recognize bullying, see it as an emergency that requires their action, tell adults, and take action. This action could be surrounding the bully, standing tall, making eye contact, having a dismissive retort, or asking questions that require the bully to think, such as “What do you want to happen by doing this?” We can coach our patients and their parents on these principles as well as advising schools.

Children need to be told that those being put down or held down – especially those like them – have strengths; have made discoveries; have produced writings, art, and music; have shown military bravery, moral leadership, and resistance to discrimination, but it is not the time to show strength when confronted by a gun or police. We can use and arm parents with examples to discuss strengths and accomplishments to help buffer the child from internalization of racist stereotypes. Children need positive role models who look like them; parents can seek out diverse professionals in their children’s lives, such as dentists, doctors, teachers, clergy, mentors, or coaches. We, and parents, can ensure that dolls and books are available, and that the children’s shows, movies, and video games are watched together and include diverse people doing good or brave things. These exposures also are key to all children becoming anti-racist.

Parents can be advised to initiate discussion of racism because children, detecting adult discomfort, may avoid the topic. We can encourage families to give their point of view; otherwise children simply absorb those of peers or the press. Parents should tell their children, “I want you to be able to talk about it if someone is mean or treats you unfairly because of [the color of your skin, your religion, your sex, your disability, etc.]. You might feel helpless, or angry, which is natural. We need to talk about this so you can feel strong. Then we can plan on what we are going to do.” The “sandwich” method of “ask-give information-ask what they think” can encourage discussion and correct misperceptions.

Racist policies have succeeded partly by adult “bullies” dehumanizing the “other.” Most children can consider someone else’s point of view by 4½ years old, shaped with adult help. Parents can begin by telling babies, “That hurts, doesn’t it?” asking toddlers and older, “How would you feel if ... [someone called you a name just because of having red hair]?” or “How do you think she feels when ... [someone pushes her out of line because she wears certain clothes]?” in cases of grabbing, not sharing, hitting, bullying, etc. Older children and teens can analyze more abstract situations when asked, “What if you were the one who ... [got expelled for mumbling about the teacher]?” or “What if that were your sister?” or “How would the world be if everyone ... [got a chance to go to college]?” We can encourage parents to propose these mental exercises to build the child’s perspective-taking while conveying their opinions.

Experiences, including through media, may increase or decrease fear; the child needs to have a supportive person moderating the exposure, providing a positive interpretation, and protecting the child from overwhelm, if needed.

Experiences are insufficient for developing anti-racist attitudes; listening and talking are needed. The first step is to ask children about what they notice, think, and feel about situations reflecting racism, especially as they lack words for these complicated observations. There are television, Internet, and newspaper examples of both racism and anti-racism that can be fruitfully discussed. We can recommend watching or reading together, and asking questions such as, “Why do you think they are shouting [protesting]?” “How do you think the [victim, police] felt?” or “What do you think should be done about this?”

It is important to acknowledge the child’s confusion, fear, anxiety, sadness, or anger as normal and appropriate, not dismissing, too quickly reassuring, or changing the subject, even though it’s uncomfortable.

Physicians and nurse practitioners can make a difference by being aware of our privilege and biases, being open, modeling discussion, screening for impact, offering strategies, advocating with schools, and providing resources such as therapy or legal counsel, as for other social determinants of health.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (https://www.site.chadis.com/). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at pdnews@mdedge.com.

Can we help our pediatric patients with the complicated problems of racism, especially if we are privileged (and even white) professionals? We may not have experienced discrimination, but we can still advise and address it. Racist discrimination, fear, trauma, or distress may produce or exacerbate conditions we are treating. I have found it often revealing to ask: “Have you, your child, or your family had an experience with racism that may be contributing to today’s concern?”

Tverdokhlib/Shutterstock

Three levels of racism impact children’s health and health care: “structural or institutional” policies that influence social determinants of health; “personally mediated” differential treatment based on assumptions about one’s abilities, motives, or intents; and the resulting “internalization” of stereotypes into one’s identity, undermining confidence, self-esteem, and mental health. We can help advocate about structural racism and ensure equity within our offices, but how best to counsel the families and children themselves?

Racism includes actions of “assigning value based on the social interpretation of how a person looks” (Ethn Dis. 2008;18[4]:496-504). “Social interpretations” develop from an early age. Newborns detect differences in appearance and may startle or cry seeing a parent’s drastic haircut or new hat. Parents generally know to use soothing words and tone, bring the difference into view gradually, smile and comfort the child, and explain the change; these are good skills for later, too. Infants notice skin color, which, unlike clothes, is a stable feature by which to recognize parents. Social interpretation of these differences is cued from the parents’ feelings and reactions. Adults naturally transmit biases from their own past unless they work to dampen them. If the parent was taught to regard “other” as negative or is generally fearful, the child mirrors this. Working to reduce racism thus requires parents (and professionals) to examine their prejudices to be able to convey positive or neutral reactions to people who are different. Parents need to show curiosity, positive affect, and comfort about people who are different, and do well to seek contact and friendships with people from other groups and include their children in these relationships. We can encourage this outreach plus ensure diversity and respectful interactions in our offices.

Children from age 3 years value fairness and are upset seeing others treated unfairly – easily understanding “not fair” or “mean.” If the person being hurt is like them in race, ethnicity, religion, gender, or sexual preference, they also fear for themselves, family, and friends. Balance is needed in discussing racism to avoid increasing fear or overpromising as risks are real and solutions difficult. Children look to adults for understanding and evidence of action to feel safer, rather than helpless. We should state that leaders are working on “making the rules more fair,” ensuring that people “won’t be allowed do it again,” and “teaching that everyone deserves respect.” Even better, parents and children can generate ideas about child actions, giving them some power as an antidote to anxiety. Age-related possibilities might include drawing a picture of people getting along, talking at show-and-tell, writing a note to officials, making a protest sign, posting thoughts on Facebook, or protesting.

With age, the culture increasingly influences a child’s attitudes. Children see lots of teasing and bullying based on differences from being overweight or wearing glasses, to skin color. It is helpful to interpret for children that bullies are insecure, or sometimes have been hurt, and they put other people down to feel better than someone else. Thinking about racist acts this way may reduce the desire for revenge and a cycle of aggression. Effective anti-bullying programs help children recognize bullying, see it as an emergency that requires their action, tell adults, and take action. This action could be surrounding the bully, standing tall, making eye contact, having a dismissive retort, or asking questions that require the bully to think, such as “What do you want to happen by doing this?” We can coach our patients and their parents on these principles as well as advising schools.

Children need to be told that those being put down or held down – especially those like them – have strengths; have made discoveries; have produced writings, art, and music; have shown military bravery, moral leadership, and resistance to discrimination, but it is not the time to show strength when confronted by a gun or police. We can use and arm parents with examples to discuss strengths and accomplishments to help buffer the child from internalization of racist stereotypes. Children need positive role models who look like them; parents can seek out diverse professionals in their children’s lives, such as dentists, doctors, teachers, clergy, mentors, or coaches. We, and parents, can ensure that dolls and books are available, and that the children’s shows, movies, and video games are watched together and include diverse people doing good or brave things. These exposures also are key to all children becoming anti-racist.

Parents can be advised to initiate discussion of racism because children, detecting adult discomfort, may avoid the topic. We can encourage families to give their point of view; otherwise children simply absorb those of peers or the press. Parents should tell their children, “I want you to be able to talk about it if someone is mean or treats you unfairly because of [the color of your skin, your religion, your sex, your disability, etc.]. You might feel helpless, or angry, which is natural. We need to talk about this so you can feel strong. Then we can plan on what we are going to do.” The “sandwich” method of “ask-give information-ask what they think” can encourage discussion and correct misperceptions.

Racist policies have succeeded partly by adult “bullies” dehumanizing the “other.” Most children can consider someone else’s point of view by 4½ years old, shaped with adult help. Parents can begin by telling babies, “That hurts, doesn’t it?” asking toddlers and older, “How would you feel if ... [someone called you a name just because of having red hair]?” or “How do you think she feels when ... [someone pushes her out of line because she wears certain clothes]?” in cases of grabbing, not sharing, hitting, bullying, etc. Older children and teens can analyze more abstract situations when asked, “What if you were the one who ... [got expelled for mumbling about the teacher]?” or “What if that were your sister?” or “How would the world be if everyone ... [got a chance to go to college]?” We can encourage parents to propose these mental exercises to build the child’s perspective-taking while conveying their opinions.

Experiences, including through media, may increase or decrease fear; the child needs to have a supportive person moderating the exposure, providing a positive interpretation, and protecting the child from overwhelm, if needed.

Experiences are insufficient for developing anti-racist attitudes; listening and talking are needed. The first step is to ask children about what they notice, think, and feel about situations reflecting racism, especially as they lack words for these complicated observations. There are television, Internet, and newspaper examples of both racism and anti-racism that can be fruitfully discussed. We can recommend watching or reading together, and asking questions such as, “Why do you think they are shouting [protesting]?” “How do you think the [victim, police] felt?” or “What do you think should be done about this?”

It is important to acknowledge the child’s confusion, fear, anxiety, sadness, or anger as normal and appropriate, not dismissing, too quickly reassuring, or changing the subject, even though it’s uncomfortable.

Physicians and nurse practitioners can make a difference by being aware of our privilege and biases, being open, modeling discussion, screening for impact, offering strategies, advocating with schools, and providing resources such as therapy or legal counsel, as for other social determinants of health.
 

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (https://www.site.chadis.com/). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at pdnews@mdedge.com.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists and intensivists to understand their approach to ordering thromboprophylaxis in acutely ill medical patients for the purpose of reducing risk of VTE. Specifically, this issue focuses on the extent to which management practice has evolved given the introduction of novel anticoagulants. The objectives of this research are to:

• Understand current practice related to ordering thromboprophylaxis, as well as the therapies used with acutely ill medical patients.
• Understand the attitudes toward thromboprophylaxis from a risk and benefit standpoint that underlie decision-making related to deployment of therapy.
• Assess therapeutic, clinical, and administrative factors that impact management choices and the adoption of novel anticoagulants.
• Assess familiarity with and influence of the MAGELLAN study.
• Identify differences in management based on practice tenure and setting (academic vs community-based).

Read the full issue

In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists and intensivists to understand their approach to ordering thromboprophylaxis in acutely ill medical patients for the purpose of reducing risk of VTE. Specifically, this issue focuses on the extent to which management practice has evolved given the introduction of novel anticoagulants. The objectives of this research are to:

• Understand current practice related to ordering thromboprophylaxis, as well as the therapies used with acutely ill medical patients.
• Understand the attitudes toward thromboprophylaxis from a risk and benefit standpoint that underlie decision-making related to deployment of therapy.
• Assess therapeutic, clinical, and administrative factors that impact management choices and the adoption of novel anticoagulants.
• Assess familiarity with and influence of the MAGELLAN study.
• Identify differences in management based on practice tenure and setting (academic vs community-based).

Read the full issue

In this issue of CHEST Clinical Perspectives, CHEST is undertaking primary research with pulmonologists and intensivists to understand their approach to ordering thromboprophylaxis in acutely ill medical patients for the purpose of reducing risk of VTE. Specifically, this issue focuses on the extent to which management practice has evolved given the introduction of novel anticoagulants. The objectives of this research are to:

• Understand current practice related to ordering thromboprophylaxis, as well as the therapies used with acutely ill medical patients.
• Understand the attitudes toward thromboprophylaxis from a risk and benefit standpoint that underlie decision-making related to deployment of therapy.
• Assess therapeutic, clinical, and administrative factors that impact management choices and the adoption of novel anticoagulants.
• Assess familiarity with and influence of the MAGELLAN study.
• Identify differences in management based on practice tenure and setting (academic vs community-based).

Read the full issue

Women and girls aged 13 years and older with no current diagnosis of anxiety should be screened routinely for anxiety, according to a new recommendation from the Women’s Preventive Services Initiative.

The lifetime prevalence of anxiety disorders in women in the United States is 40%, approximately twice that of men, and anxiety can be a manifestation of underlying issues including posttraumatic stress, sexual harassment, and assault, wrote Kimberly D. Gregory, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues on behalf of the Women’s Preventive Services Initiative (WPSI), a national coalition of women’s health professional organizations and patient representatives.

“The WPSI based its rationale for anxiety screening on several considerations,” the researchers noted. “Anxiety disorders are the most prevalent mental health disorders in women, and the problems created by untreated anxiety can impair function in all areas of a woman’s life.”

“Effective screening may lead to earlier or timelier treatment (including behavioral and medical interventions) and result in improved clinical outcomes, such as symptoms, function, and quality of life. Screening may also lead to the detection of associated conditions, such as depression and posttraumatic stress disorder, which may also require treatment,” they wrote.

To support the recommendation, the researchers evaluated data from 33 studies and 2 systematic reviews for a total of 171 studies. Most studies included screening instruments that involved clinician- or patient-administered questionnaires designed for use in clinical practice. Although none of the studies evaluated the overall effectiveness versus harm of screening for anxiety, the strength of evidence for the effectiveness of anxiety treatment ranged from moderate to high, and the evidence of harms ranged from low for cognitive-behavioral therapy to moderate for anxiety medications.

“Overall, the WPSI determined that the balance of benefits and harms would likely be favorable on the basis of the high prevalence of anxiety in women; its substantial effect on health, function, and quality of life; and evidence on the accuracy of screening instruments in primary care settings and the effectiveness and harms of treatment,” the researchers wrote.

Although anxiety screening is not currently routine in clinical practice in the United States, such screening could be done quickly and efficiently as part of an intake visit in a primary care or obstetric setting, using a brief screening tool similar to those used for depression, the researchers wrote. The goal of anxiety screening, as with depression screening, is to identify those who need further evaluation to diagnose or rule out an anxiety disorder.

“A revised version [of the draft recommendation] was adopted by the Health Resources and Services Administration in December 2019; it will be incorporated into the summary of covered benefits for preventive services without cost sharing as required by the Patient Protection and Affordable Care Act immediately or no later than 1 January 2021, depending on individual coverage,” the researchers noted.

“Covered benefits apply to most group health plans and issuers of group and individual health insurance coverage, as well as to persons who qualify for Medicaid on the basis of Medicaid expansion under the Affordable Care Act,” they wrote.

“Because anxiety disorders can be successfully treated, early detection through the use of a brief questionnaire could prevent years of symptoms and impairment in the lives of women at every stage of life,” they concluded.

Aaron Sutton, LCSW, a behavioral health consultant at Abington (Pa.) Hospital–Jefferson Health, expressed support for the guidelines in an interview.

“With almost half of all women experiencing an anxiety disorder sometime in their life, effective recognition and treatment of anxiety disorders is needed,” he said.

Mr. Sutton described treatment as being “fairly benign” with the initial approach being cognitive-behavioral therapy, a form of psychological talk therapy, and first-line pharmacologic therapies being SSRIs and serotonin norepinephrine reuptake inhibitors.

Mr. Sutton also explained how he expects effective screening and treatment will benefit women with anxiety and the health care system.

“Women will see improvement in areas such as personal relationships, work, school, and social settings. The health care system will see benefits as costs related to anxiety disorders, be it direct or indirect, are in the billions of dollars,” he said.

Although screening for anxiety will increase the workload of primary care physicians, anxiety screening should be included and could perhaps be administered in conjunction with the routine depression screening already recommended as part of primary care visits, Mr. Sutton noted.

“Anxiety disorders can be successfully treated, and early detection can prevent years of symptoms and impairment,” he emphasized.

“Anxiety often occurs among adolescents and adult women and often becomes a chronic problem with impairments,” said Cynthia Pfeffer, MD, professor of psychiatry at Weill Cornell Medicine, New York, in an interview. “Screening for anxiety could identify and enable planning to decrease and prevent this impairing prevalent condition and its associated problems. For example, anxiety can impair adolescents’ academic and social functioning and if this is lasting also impair their success in work and future planning for families. There are successful treatments for anxiety and identification of individuals at an early time may prevent impairments in daily functioning.”

Dr. Pfeffer noted that steps to overcome barriers to prevention and treatment for anxiety include “educating health care professionals about the problems caused from anxiety, learning means to identify and diagnose anxiety, and developing proficiency in offering methods to prevent and intervene for women with symptoms of anxiety.”

The take-home message for clinicians is that anxiety is prevalent among females of all ages and often begins early and becomes chronic.

“There are excellent treatments including psychotherapy and medication that can decrease and prevent anxiety,” she emphasized. “Training practicing clinicians including MDs as well as other professionals in the health care system about anxiety will enhance the wellbeing of women.”

More research is needed to evaluate methods used during health care visits for anxiety screening and treatment in order to determine valid means of preventing the impairments associated with anxiety, Dr. Pfeffer said.

Mr. Sutton noted that no trials “have evaluated overall effectiveness or potential harms including labeling, misdiagnosis, and overdiagnosis.” Other areas in need of research include the changes in incidence and prevalence of anxiety over time, as well as specific risk factors including marriage, divorce, pregnancy, and childbirth, he added.

The research for the recommendation was supported by the Health Resources and Services Administration. The researchers had no financial conflicts to disclose. Mr. Sutton had no financial conflicts to disclose. Dr. Pfeffer has written extensively on depression and anxiety in children, adolescents, and adults. She had no financial conflicts to disclose.

SOURCE: Gregory KD et al. Ann Intern Med. 2020 June 9. doi: 10.7326/M20-0580.

Women and girls aged 13 years and older with no current diagnosis of anxiety should be screened routinely for anxiety, according to a new recommendation from the Women’s Preventive Services Initiative.

The lifetime prevalence of anxiety disorders in women in the United States is 40%, approximately twice that of men, and anxiety can be a manifestation of underlying issues including posttraumatic stress, sexual harassment, and assault, wrote Kimberly D. Gregory, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues on behalf of the Women’s Preventive Services Initiative (WPSI), a national coalition of women’s health professional organizations and patient representatives.

“The WPSI based its rationale for anxiety screening on several considerations,” the researchers noted. “Anxiety disorders are the most prevalent mental health disorders in women, and the problems created by untreated anxiety can impair function in all areas of a woman’s life.”

“Effective screening may lead to earlier or timelier treatment (including behavioral and medical interventions) and result in improved clinical outcomes, such as symptoms, function, and quality of life. Screening may also lead to the detection of associated conditions, such as depression and posttraumatic stress disorder, which may also require treatment,” they wrote.

To support the recommendation, the researchers evaluated data from 33 studies and 2 systematic reviews for a total of 171 studies. Most studies included screening instruments that involved clinician- or patient-administered questionnaires designed for use in clinical practice. Although none of the studies evaluated the overall effectiveness versus harm of screening for anxiety, the strength of evidence for the effectiveness of anxiety treatment ranged from moderate to high, and the evidence of harms ranged from low for cognitive-behavioral therapy to moderate for anxiety medications.

“Overall, the WPSI determined that the balance of benefits and harms would likely be favorable on the basis of the high prevalence of anxiety in women; its substantial effect on health, function, and quality of life; and evidence on the accuracy of screening instruments in primary care settings and the effectiveness and harms of treatment,” the researchers wrote.

Although anxiety screening is not currently routine in clinical practice in the United States, such screening could be done quickly and efficiently as part of an intake visit in a primary care or obstetric setting, using a brief screening tool similar to those used for depression, the researchers wrote. The goal of anxiety screening, as with depression screening, is to identify those who need further evaluation to diagnose or rule out an anxiety disorder.

“A revised version [of the draft recommendation] was adopted by the Health Resources and Services Administration in December 2019; it will be incorporated into the summary of covered benefits for preventive services without cost sharing as required by the Patient Protection and Affordable Care Act immediately or no later than 1 January 2021, depending on individual coverage,” the researchers noted.

“Covered benefits apply to most group health plans and issuers of group and individual health insurance coverage, as well as to persons who qualify for Medicaid on the basis of Medicaid expansion under the Affordable Care Act,” they wrote.

“Because anxiety disorders can be successfully treated, early detection through the use of a brief questionnaire could prevent years of symptoms and impairment in the lives of women at every stage of life,” they concluded.

Aaron Sutton, LCSW, a behavioral health consultant at Abington (Pa.) Hospital–Jefferson Health, expressed support for the guidelines in an interview.

“With almost half of all women experiencing an anxiety disorder sometime in their life, effective recognition and treatment of anxiety disorders is needed,” he said.

Mr. Sutton described treatment as being “fairly benign” with the initial approach being cognitive-behavioral therapy, a form of psychological talk therapy, and first-line pharmacologic therapies being SSRIs and serotonin norepinephrine reuptake inhibitors.

Mr. Sutton also explained how he expects effective screening and treatment will benefit women with anxiety and the health care system.

“Women will see improvement in areas such as personal relationships, work, school, and social settings. The health care system will see benefits as costs related to anxiety disorders, be it direct or indirect, are in the billions of dollars,” he said.

Although screening for anxiety will increase the workload of primary care physicians, anxiety screening should be included and could perhaps be administered in conjunction with the routine depression screening already recommended as part of primary care visits, Mr. Sutton noted.

“Anxiety disorders can be successfully treated, and early detection can prevent years of symptoms and impairment,” he emphasized.

“Anxiety often occurs among adolescents and adult women and often becomes a chronic problem with impairments,” said Cynthia Pfeffer, MD, professor of psychiatry at Weill Cornell Medicine, New York, in an interview. “Screening for anxiety could identify and enable planning to decrease and prevent this impairing prevalent condition and its associated problems. For example, anxiety can impair adolescents’ academic and social functioning and if this is lasting also impair their success in work and future planning for families. There are successful treatments for anxiety and identification of individuals at an early time may prevent impairments in daily functioning.”

Dr. Pfeffer noted that steps to overcome barriers to prevention and treatment for anxiety include “educating health care professionals about the problems caused from anxiety, learning means to identify and diagnose anxiety, and developing proficiency in offering methods to prevent and intervene for women with symptoms of anxiety.”

The take-home message for clinicians is that anxiety is prevalent among females of all ages and often begins early and becomes chronic.

“There are excellent treatments including psychotherapy and medication that can decrease and prevent anxiety,” she emphasized. “Training practicing clinicians including MDs as well as other professionals in the health care system about anxiety will enhance the wellbeing of women.”

More research is needed to evaluate methods used during health care visits for anxiety screening and treatment in order to determine valid means of preventing the impairments associated with anxiety, Dr. Pfeffer said.

Mr. Sutton noted that no trials “have evaluated overall effectiveness or potential harms including labeling, misdiagnosis, and overdiagnosis.” Other areas in need of research include the changes in incidence and prevalence of anxiety over time, as well as specific risk factors including marriage, divorce, pregnancy, and childbirth, he added.

The research for the recommendation was supported by the Health Resources and Services Administration. The researchers had no financial conflicts to disclose. Mr. Sutton had no financial conflicts to disclose. Dr. Pfeffer has written extensively on depression and anxiety in children, adolescents, and adults. She had no financial conflicts to disclose.

SOURCE: Gregory KD et al. Ann Intern Med. 2020 June 9. doi: 10.7326/M20-0580.

Women and girls aged 13 years and older with no current diagnosis of anxiety should be screened routinely for anxiety, according to a new recommendation from the Women’s Preventive Services Initiative.

The lifetime prevalence of anxiety disorders in women in the United States is 40%, approximately twice that of men, and anxiety can be a manifestation of underlying issues including posttraumatic stress, sexual harassment, and assault, wrote Kimberly D. Gregory, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues on behalf of the Women’s Preventive Services Initiative (WPSI), a national coalition of women’s health professional organizations and patient representatives.

“The WPSI based its rationale for anxiety screening on several considerations,” the researchers noted. “Anxiety disorders are the most prevalent mental health disorders in women, and the problems created by untreated anxiety can impair function in all areas of a woman’s life.”

“Effective screening may lead to earlier or timelier treatment (including behavioral and medical interventions) and result in improved clinical outcomes, such as symptoms, function, and quality of life. Screening may also lead to the detection of associated conditions, such as depression and posttraumatic stress disorder, which may also require treatment,” they wrote.

To support the recommendation, the researchers evaluated data from 33 studies and 2 systematic reviews for a total of 171 studies. Most studies included screening instruments that involved clinician- or patient-administered questionnaires designed for use in clinical practice. Although none of the studies evaluated the overall effectiveness versus harm of screening for anxiety, the strength of evidence for the effectiveness of anxiety treatment ranged from moderate to high, and the evidence of harms ranged from low for cognitive-behavioral therapy to moderate for anxiety medications.

“Overall, the WPSI determined that the balance of benefits and harms would likely be favorable on the basis of the high prevalence of anxiety in women; its substantial effect on health, function, and quality of life; and evidence on the accuracy of screening instruments in primary care settings and the effectiveness and harms of treatment,” the researchers wrote.

Although anxiety screening is not currently routine in clinical practice in the United States, such screening could be done quickly and efficiently as part of an intake visit in a primary care or obstetric setting, using a brief screening tool similar to those used for depression, the researchers wrote. The goal of anxiety screening, as with depression screening, is to identify those who need further evaluation to diagnose or rule out an anxiety disorder.

“A revised version [of the draft recommendation] was adopted by the Health Resources and Services Administration in December 2019; it will be incorporated into the summary of covered benefits for preventive services without cost sharing as required by the Patient Protection and Affordable Care Act immediately or no later than 1 January 2021, depending on individual coverage,” the researchers noted.

“Covered benefits apply to most group health plans and issuers of group and individual health insurance coverage, as well as to persons who qualify for Medicaid on the basis of Medicaid expansion under the Affordable Care Act,” they wrote.

“Because anxiety disorders can be successfully treated, early detection through the use of a brief questionnaire could prevent years of symptoms and impairment in the lives of women at every stage of life,” they concluded.

Aaron Sutton, LCSW, a behavioral health consultant at Abington (Pa.) Hospital–Jefferson Health, expressed support for the guidelines in an interview.

“With almost half of all women experiencing an anxiety disorder sometime in their life, effective recognition and treatment of anxiety disorders is needed,” he said.

Mr. Sutton described treatment as being “fairly benign” with the initial approach being cognitive-behavioral therapy, a form of psychological talk therapy, and first-line pharmacologic therapies being SSRIs and serotonin norepinephrine reuptake inhibitors.

Mr. Sutton also explained how he expects effective screening and treatment will benefit women with anxiety and the health care system.

“Women will see improvement in areas such as personal relationships, work, school, and social settings. The health care system will see benefits as costs related to anxiety disorders, be it direct or indirect, are in the billions of dollars,” he said.

Although screening for anxiety will increase the workload of primary care physicians, anxiety screening should be included and could perhaps be administered in conjunction with the routine depression screening already recommended as part of primary care visits, Mr. Sutton noted.

“Anxiety disorders can be successfully treated, and early detection can prevent years of symptoms and impairment,” he emphasized.

“Anxiety often occurs among adolescents and adult women and often becomes a chronic problem with impairments,” said Cynthia Pfeffer, MD, professor of psychiatry at Weill Cornell Medicine, New York, in an interview. “Screening for anxiety could identify and enable planning to decrease and prevent this impairing prevalent condition and its associated problems. For example, anxiety can impair adolescents’ academic and social functioning and if this is lasting also impair their success in work and future planning for families. There are successful treatments for anxiety and identification of individuals at an early time may prevent impairments in daily functioning.”

Dr. Pfeffer noted that steps to overcome barriers to prevention and treatment for anxiety include “educating health care professionals about the problems caused from anxiety, learning means to identify and diagnose anxiety, and developing proficiency in offering methods to prevent and intervene for women with symptoms of anxiety.”

The take-home message for clinicians is that anxiety is prevalent among females of all ages and often begins early and becomes chronic.

“There are excellent treatments including psychotherapy and medication that can decrease and prevent anxiety,” she emphasized. “Training practicing clinicians including MDs as well as other professionals in the health care system about anxiety will enhance the wellbeing of women.”

More research is needed to evaluate methods used during health care visits for anxiety screening and treatment in order to determine valid means of preventing the impairments associated with anxiety, Dr. Pfeffer said.

Mr. Sutton noted that no trials “have evaluated overall effectiveness or potential harms including labeling, misdiagnosis, and overdiagnosis.” Other areas in need of research include the changes in incidence and prevalence of anxiety over time, as well as specific risk factors including marriage, divorce, pregnancy, and childbirth, he added.

The research for the recommendation was supported by the Health Resources and Services Administration. The researchers had no financial conflicts to disclose. Mr. Sutton had no financial conflicts to disclose. Dr. Pfeffer has written extensively on depression and anxiety in children, adolescents, and adults. She had no financial conflicts to disclose.

SOURCE: Gregory KD et al. Ann Intern Med. 2020 June 9. doi: 10.7326/M20-0580.

A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.

Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.

Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.

In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.

Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.

In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).

Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.

“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.

The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.

“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.

“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.

Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.

“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.

SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.

A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.

Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.

Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.

In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.

Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.

In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).

Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.

“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.

The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.

“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.

“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.

Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.

“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.

SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.

A diet higher in fat, sugar, and milk was associated with having acne in a cross-sectional study of approximately 24,000 adults in France.

Acne in adults has been associated with social, emotional, and psychological consequences similar to those found with chronic diseases such as asthma, arthritis, epilepsy, and diabetes, wrote Laetitia Penso, MSc, of the University of Paris in Bobigny, France, and colleagues.

Although acne patients may believe that eating certain foods exacerbates acne, data on the effects of nutrition on acne, including associations between acne and a high-glycemic diet, are limited and have produced conflicting results, they noted.

In their study, published in JAMA Dermatology, the researchers identified 24,452 adults who participated in the NutriNet-Santé study, an ongoing, web-based study in France. Approximately 75% of the participants were women, the average age was 57 years, and 46% reported past or current acne.

Participants responded to an 11-item questionnaire between November 2008 and July 2019. Questions were related to the occurrence and diagnosis of acne, as well as medical history. Based on their acne status, participants were identified as falling into the categories of never acne, past acne, or current acne, and their dietary intake was assessed at baseline and every 6 months using three nonconsecutive 24-hour dietary records for 2 weekdays and 1 weekend day.

In an analysis, after adjustment for confounders, current acne was significantly associated with consumption of fatty and sugary foods (per portion, adjusted odds ratio, 1.54; P = .01), as well as with consumption of sugary drinks (per glass, aOR, 1.18; P = .04) and milk (per glass, aOR, 1.12; P = .04). In addition, carbohydrate intake and saturated fatty acid intake were significantly associated with current acne (aOR, 1.43; P = .02; and aOR, 3.90; P = .048, respectively).

Three dietary patterns accounted for 42% of the total variability, the researchers said. A healthy pattern of higher fruit, vegetable, and fish intake accounted for 18%, a fatty and sugary pattern of higher fat and sugar intake (including chocolate) accounted for 13%, and an animal product and cereal pattern of higher intake of meat, milk, and refined cereals accounted for 11%, they explained.

“The results of our study appear to support the hypothesis that the Western diet (rich in animal products and fatty and sugary foods) is associated with the presence of acne in adulthood,” the researchers concluded. Possible explanations for the findings include the effects of a high glycemic-load diet on circulating IGF-1 and insulin, which ultimately increases both oxidative stress and inflammation that promotes the development of acne, they noted.

The study findings were limited by several factors including the use of relatively homogenous younger and female patient population and the reliance on self-reported acne, as well as the observational design, which did not allow for identification of direct, causal associations between diet and acne, the researchers noted. Larger studies are needed to examine the relationship between diet and adult acne to inform prevention and treatment, they wrote.

“Much of the previous literature on the role of diet in acne has focused on the association of milk consumption and high glycemic-load diet with acne,” John S. Barbieri, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, wrote in an accompanying editorial.

Dr. Barbieri acknowledged the inability to make causal associations given the study design and noted that dietary interventions should be implemented with caution because of the potential for other effects such as reduced calcium or vitamin D.

“Nevertheless, given the potential overall health benefits of a healthy or low glycemic-load diet, and 2 small trials supporting its effectiveness in acne, a low glycemic-load diet is a reasonable recommendation for patients looking for dietary modifications that may improve their acne,” he said.

Dr. Barbieri said that he was encouraged to see that the study findings reflected previous research identifying an association between acne and high-glycemic load foods, as well as milk consumption, but he emphasized that more research is needed before general recommendations about diet and acne can be made.

“Trials are needed to evaluate whether dietary interventions can improve or prevent acne and how the effect size of such interventions compares with other standard treatment modalities,” he emphasized.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Barbieri disclosed support from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and from a Pfizer Fellowship grant to the Trustees of the University of Pennsylvania.

SOURCE: Penso L et al. JAMA Dermatol. 2020 June 10. doi: 10.1001/jamadermatol.2020.1602.

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

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

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

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

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

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

A 62-year-old man with metastatic non–small cell lung cancer (NSCLC) presented to the Emergency Department with 3 days of progressive generalized weakness, anorexia, and nonbloody diarrhea. He denied fever, chills, nausea, vomiting, cough, shortness of breath, or abdominal pain. He had no sick contacts.

One diagnostic approach for patients with cancer who present with new symptoms is to consider diagnoses both related and unrelated to the cancer. Cancer-related diagnoses can include the broad categories of complications related to the tumor itself (such as mass effect), paraneoplastic phenomena, or treatment-related complications (such as infection from immunosuppression or chemotherapy toxicity).

For this patient with metastatic NSCLC, weakness, anorexia, and diarrhea are unlikely to be related to mass effect unless the patient has peritoneal metastases (an uncommon complication of NSCLC) with carcinomatosis-associated diarrhea.

Paraneoplastic phenomena, such as hypercalcemia or hyponatremia from the syndrome of inappropriate antidiuretic hormone (SIADH), are common with NSCLC and could both lead to weakness and anorexia. Hematologic consequences of NSCLC (or its treatment) include anemia, thrombosis, and thrombotic microangiopathy (TMA), though diarrhea, in the absence of abdominal pain or hematochezia, would be unexpected.

Weakness, anorexia, and diarrhea may also be symptoms of chemotherapy toxicity or an infection resulting from immunosuppression. It would be important to know what specific treatment the patient has received. Chemotherapy commonly causes neutropenia and predisposes to rapidly progressive infections, while immunotherapies have other toxicities. Diarrhea is a common toxicity of the checkpoint inhibitors and anaplastic lymphoma kinase (ALK) inhibitors that are frequently used to treat metastatic NSCLC. Checkpoint inhibitors also are known to cause a wide range of autoimmune phenomena including colitis.

Finally, the patient’s symptoms may be unrelated to the cancer. Weakness, anorexia, and nonbloody diarrhea could be signs of viral or bacterial gastroenteritis or Clostridioides difficile colitis particularly with frequent healthcare contact or antimicrobial use.

Two days prior, he had been diagnosed with nonsevere Clostridioides difficile colitis in an acute care clinic. He was started on oral metronidazole, but his diarrhea worsened over the next day and was accompanied by weakness and anorexia. Additional past medical history included untreated hepatitis C infection, chronic kidney disease stage 3, seizure disorder, and left lung NSCLC (adenocarcinoma). The lung cancer was diagnosed 8 months prior when he had presented with hemoptysis and 3 months of progressive constitutional symptoms. Imaging at that time revealed metastases to the contralateral lung and regional lymph nodes, as well as vertebrae, ribs, and pelvis. He had no abdominal metastases. He was initially treated with carboplatin and paclitaxel. After a partial response to initial chemotherapy, he developed peripheral neuropathy and was switched to gemcitabine 12 weeks ago. He received five cycles of gemcitabine over 10 weeks. He was last administered gemcitabine 2 weeks prior. He had not received any additional chemotherapy or immunotherapy. He had a 40 pack-year history of smoking, but quit when diagnosed with cancer. He did not drink alcohol. He had no recent travel or sick contacts. He was not on any medications. He was homeless but staying with family members in the area. Additional review of systems was negative for recent bleeding, bruising, hemoptysis, melena, hematochezia, or hematuria.

Recent treatment with gemcitabine could contribute to the presentation in a number of ways. First, gemcitabine is associated with myelosuppression and neutropenia that could predispose him to infectious colitis. Second, gemcitabine is known to cause anemia, anorexia, diarrhea, and fatigue. Third, gemcitabine may also cause renal injury that can contribute to worsening anemia. He may be at greater risk of anemia and renal toxicity because of preexisting chronic kidney disease. Finally, gemcitabine can rarely cause TMA with characteristics that mimic the hemolytic-uremic syndrome with microangiopathic hemolytic anemia, mild thrombocytopenia, and severe acute kidney injury (AKI).

In addition, worsening infectious colitis could certainly explain his presenting symptoms. At this point, local mass effect seems unlikely despite his metastatic disease. Lastly, it should be noted that, in an immunosuppressed cancer patient, multiple problems could be present at the same time. Laboratory testing should evaluate for hypercalcemia, SIADH, hematologic indexes, and renal function. If initial laboratory evaluation is unrevealing, abdominal imaging may be needed to assess for carcinomatosis, complications from colitis, typhlitis, abscess, or perforation.

On physical examination, the patient appeared fatigued. His temperature was 36.8°C, blood pressure 158/72 mm Hg, pulse 88 beats per minute, respiratory rate 16 breaths per minute, and oxygen saturation was 96% while breathing ambient air. There was neither scleral icterus nor conjunctival injection but he had mild conjunctival pallor. Cardiovascular and lung examinations were normal. Abdominal exam revealed normal bowel sounds without tenderness or organomegaly. He had no supraclavicular, axillary, or inguinal lymphadenopathy. He was alert and oriented. Cranial nerves II through XII were intact. He had decreased muscle bulk in his extremities without focal weakness. Gait and reflexes were not tested.

Initial laboratory testing revealed a white blood cell count of 5.5 K/mm³, hemoglobin of 5 g/dL (hemoglobin 1 month prior was 10.1 g/dL), and platelet count of 20 K/mm³ (platelet count 1 month prior was 246 K/mm³). Creatinine was 3.9 mg/dL (compared with a baseline of 1.8 mg/dL), and blood urea nitrogen was 39 mg/dL. His sodium was 137 mEq/L, potassium 4.2 mEq/L, chloride 105 mEq/L, bicarbonate 22 mEq/L, and thyroid stimulating hormone 0.9 mU/L. His total protein was 4.9 g/dL, albumin 2.1 g/dL, alkaline phosphatase 60 IU/L, alanine aminotransferase 17 IU/L, aspartate aminotransferase 60 IU/L, direct bilirubin 0.2 mg/dL, and total bilirubin 0.5 mg/dL. A chest x-ray showed no infiltrates.

The patient’s laboratory tests reveal several important new findings, including severe acute on chronic anemia, acute thrombocytopenia, and AKI, without clinical evidence of acute blood loss. These changes could be parts of a syndrome or multiple independent disorders. The most urgent priority is to evaluate for TMAs, many of which are fatal if not diagnosed and treated expeditiously. This includes thrombotic thrombocytopenic purpura (TTP), disseminated intravascular hemolysis (DIC), and atypical hemolytic uremic syndrome (aHUS). A manual review of a peripheral blood smear is required to evaluate for fragmented red blood cells (schistocytes). Thereafter, ancillary testing to confirm intravascular hemolysis would include measuring free plasma hemoglobin and lactate dehydrogenase (LDH). Additionally, in intravascular hemolysis, haptoglobin should be depleted and urinalysis should show heme-positive urine without RBCs. In this case the patient’s normal bilirubin studies argue against hemolysis; however, elevated bilirubin is variably present in hemolytic anemias depending on the liver’s ability to conjugate and excrete bilirubin, the relative degree of RBC turnover, and type of hemolysis. Patients with intravascular hemolysis lose hemoglobin directly into the urine leaving relatively little hemoglobin to be incorporated into bile once it has reached the reticuloendothelial system. This results in relatively normal bilirubin levels. More specific indicators of intravascular hemolysis include pink colored plasma on visual inspection (commonly done in the blood bank as part of assessing for hemolytic transfusion reactions), measuring plasma free hemoglobin, or by detecting hemoglobin in the urine.

If microangiopathic hemolytic anemia (MAHA) is excluded, then other causes of these laboratory abnormalities should be considered. Bleeding is the most common cause for anemia, and thrombocytopenia predisposes patients to bleeding. However, there is no evidence of bleeding in this patient, and such a rapid acute anemia is unlikely to be caused by occult blood loss alone. Concurrent anemia and thrombocytopenia could be evidence of bone marrow toxicity from chemotherapy or neoplastic infiltration. With marrow infiltration, there are typically signs on the peripheral smear of leukoerythroblastosis, with circulating nucleated red blood cells and early myeloid forms. Concurrent immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), or Evans’ Syndrome, should also be considered. AIHA would be suggested by spherocytes on the peripheral smear, elevated LDH and a positive direct antibody test (DAT).

Regarding the AKI, the patient has diarrhea, which could lead to prerenal azotemia and acute tubular necrosis. A formal urinalysis would evaluate for prerenal and intrinsic kidney disease. TMA can cause intrinsic kidney injury with a benign urinary sediment. The blood urea nitrogen-to-creatinine ratio is not elevated, but in a patient with malnutrition this may not indicate prerenal azotemia. In summary, to differentiate potential TMAs from other causes, the patient needs a blood smear, coagulation studies, and an evaluation for hemolysis, including a urinalysis for free heme and any evidence of intrinsic kidney disease.

Urinalysis showed amber-colored, dilute urine with no white blood cells, red blood cells, protein, or casts. It was positive for blood and negative for bilirubin and hemosiderin. LDH was 1,382 IU/L (reference range 135-225 IU/L), and haptoglobin was unmeasurably low. His ferritin was 2,267 ng/mL, serum iron was 57 mcg/dL, total iron-binding capacity was 241 mcg/dL, and transferrin was 162 mcg/dL. Reticulocyte count was 6% (reticulocyte index of 0.86). Vitamin B12 level was normal. DAT was negative; INR and aPTT were normal. Fibrinogen was 287 mg/dL (reference range 200-400 mg/dL), and D-dimer was 5,095 ng/mL (reference range 0-229 ng/mL).

The urinalysis shows no active sediment to suggest vasculitis or glomerulonephritis. The kidney injury could be the result of renal toxicity from free hemoglobin or as part of TMA caused by microvascular thrombosis. The dilute urine makes prerenal azotemia less likely.

There is clearly acute intravascular hemolysis occurring as evidenced by hemoglobinuria, very high LDH, and undetectable serum haptoglobin. The hemolysis is acute because chronic intravascular hemolysis would lead to positive urine hemosiderin via deposition in the renal tubules. Autoimmune hemolytic anemia is much less likely, but not ruled out, by a negative DAT.

This syndrome can be further refined from acute anemia to acute anemia with likely nonimmune intravascular hemolysis, acute thrombocytopenia, and AKI with hemoglobinuria and a bland urinary sediment. At this point, intravascular hemolysis and kidney injury could be part of a unifying diagnosis. However, this does not account for the patient’s thrombocytopenia, and TMA remains the best explanation for the constellation of findings. Review of the peripheral blood smear is urgent because evidence of MAHA would prompt urgent plasma exchange based on presumptive diagnosis of acquired TTP to later be confirmed with ADAMTS13 activity testing. Most TMAs are treated with supportive care only; TTP and aHUS have specific interventions that change the natural history of the disease (plasma exchange and anticomplement therapy, respectively). Given both the deadly natural history and opportunity to intervene with plasma exchange, patients with TMA should be treated with urgent plasma exchange until ADAMTS13 deficiency is confirmed or refuted. One TMA that can be excluded at this point is DIC. DIC in its acute and chronic forms nearly universally causes MAHA, thrombocytopenia, and consumptive coagulopathy including hypofibrinogenemia.

If MAHA is excluded, then other causes of intravascular hemolysis should be considered, along with causes of thrombocytopenia that might be occurring concurrently. Intravascular hemolysis can be further differentiated by etiologies primarily related to the RBC or whether the RBC is the innocent bystander amidst a systemic illness. RBC disorders include syndromes affecting RBC fragility like hereditary spherocytosis or RBC enzymopathies (G6PD deficiency), but these do not cause thrombocytopenia. One exception is an acquired membrane defect, paroxysmal nocturnal hemoglobinuria (PNH), in which RBCs and other blood cells become susceptible to complement-mediated lysis. Testing for PNH by peripheral blood flow cytometry should be considered if the blood film lacks schistocytes. Systemic disorders that cause intravascular hemolysis include severe burns (heat damage to RBCs), RBC trauma from “march hemoglobinuria” or mechanical heart valves, immune (antibody-mediated) hemolysis from Rh immune globulin administration, cold agglutinin disease or ABO mismatched transfusion, and infections including the intraerythrocyte parasites malaria, Bartonellosis, and Babesiosis, as well as organisms that induce RBC fragility such as Leishmaniasis, Clostridium perfringens, and Haemophilus influenzae B.

On review of additional history, the patient had not recently received blood products. He had received heparin during prior hospitalizations, but had no prior history of thrombosis. He had no history of tick exposure. Peripheral blood smear was obtained and reviewed by a hematopathologist. It showed no schistocytes or spherocytes, but demonstrated pyropoikilocytosis.

The blood smear helps narrow the differential further. The lack of schistocytes makes TMA far less likely and so plasma exchange is not urgently indicated. The differential still includes drug-­induced TMA (gemcitabine being a well-known cause for TMA) and cancer-associated TMA could still cause these findings, but plasma exchange does not improve outcomes. Acquired (immune) TTP is very unlikely unless the patient did not improve with supportive care or developed neurologic symptoms. Similarly, atypical (complement-driven) HUS would only be considered if renal failure did not improve with supportive care.

The blood smear does show a surprising finding of pyropoikilocytosis. Pyropoikilocytosis refers to changes in RBC shape (poikilocytosis) typically seen with thermal injury or rare RBC membrane structural defects. Hereditary pyropoikilocytosis, a very rare disease, is characterized by chronic hyperproliferative, compensated anemia, and occasional hemolytic crises. These crises are associated with splenomegaly, reticulocytosis, and elevated bilirubin with jaundice. As the patient has no history of similar episodes, the blood smear changes are not due to a hereditary cause and obviously not due to thermal injury (ie, severe burns). Pyropoikilocytosis has been rarely reported in drug-induced TMA and in severe bacterial bloodstream infections (most commonly Gram-negative bacilli). This patient has received gemcitabine (a known cause of drug-induced TMA) and has a recently diagnosed infection (C difficile colitis), either of which could be linked to this rare blood smear finding. Both of these syndromes would be treated with supportive care plus avoidance of future gemcitabine.

Transfusion of packed RBCs is indicated given his profound anemia and symptoms of fatigue. One should obtain further testing for cold agglutinins, PNH, and echocardiography to exclude endocarditis. If he were to become critically ill, anuric, or encephalopathic, then one could consider plasma exchange for treatment of TMA and hemoglobin-mediated AKI. Pyropoikilocytosis should be considered the result of drug-induced TMA, severe C difficile colitis, or an occult infection.

The patient was transfused packed RBCs. Because of a concern for an acute TMA such as TTP, both a hematopathologist and the consulting hematology/oncology team reviewed the peripheral blood morphology emergently. He was given aggressive fluid resuscitation and received 3 L of IV lactated ringers’ solution. An echocardiogram did not show valvular abnormalities. A renal biopsy was contraindicated because of the severe thrombocytopenia.

Given the recently confirmed C difficile colitis along with the findings of pyropoikilocytosis on the peripheral smear, toxin-mediated intravascular hemolysis from systemic C difficile infection became the leading diagnosis. Positing that the C difficile colitis was inadequately treated with oral metronidazole, aggressive treatment for C difficile was initiated with oral vancomycin in addition to intravenous metronidazole. Intravenous metronidazole was included given his elevated creatinine, presence of severe colitis on imaging, and concern he may be at risk for translocation of colonic C difficile or exotoxin into the bloodstream.

Over the course of the next 3 days, the patient’s platelet count normalized and his hemoglobin, creatinine, and symptoms of fatigue improved. Blood cultures remained negative. The patient’s rapid improvement with antibiotics supported our final diagnosis of toxin-mediated hemolysis caused by a systemic C difficile infection. On follow-up testing after hospital discharge, hemoglobin had returned to prior baseline and there was no recurrent hemolysis. Gemcitabine was considered to be a possible cause of his hemolytic anemia and was not continued in further treatment for his NSCLC.

When evaluating patients with cancer who present with fatigue, hospitalists should consider a broad list of potential causes. The differential should include etiologies directly related to the malignancy, paraneoplastic phenomena, treatment-related complications, and diseases unrelated to cancer. In addition, as the number of medications used for cancer proliferates, hospitalists must take a detailed history of the agents used and be aware of major side effects. Using this information, hospitalists may undertake a targeted approach to diagnostics while searching for a cause of fatigue.

When lab testing reveals profound anemia, hospitalists must consider syndromes that may require emergent management. Anemia can be caused by decreased RBC production, and acute anemia in the absence of clear blood loss suggests hemolysis. Moreover, the combination of elevated LDH and low haptoglobin is quite specific of hemolytic anemia.^1,2 Once hemolytic anemia is identified, DIC and TMA syndromes (such as TTP) need to be considered. The combination of hemolytic anemia and AKI may indicate a medical emergency and should prompt hospitalists to obtain an urgent peripheral blood smear to help narrow the differential.³

The absence of schistocytes on a blood smear does not rule out TTP or HUS, but does argue strongly against these diagnoses.^4,5 Of note, consultation with a hematopathologist and hematology subspecialist should be done to ensure appropriate and timely review of the peripheral blood smear.

In this case, the blood smear led to a very rare finding of pyropoikilocytosis. The unexpected result should prompt a broader review of the medical history particularly as it relates to the patient’s broader symptoms and laboratory abnormalities. Acquired pyropoikilocytosis is a very specific finding known to be associated only with hyperthermal injury (seen in burn patients), drug-induced TMA, and bacterial bloodstream infections, mainly Gram-negative toxins and Clostridioidal infections.^6-8 In this case, both drug-induced TMA and C difficile infection were considered.

Gemcitabine-induced TMA can occur with either short or long term use of the medication and can be difficult to distinguish from TTP. While both TTP and gemcitabine-induced TMA can cause thrombocytopenia, hemolytic anemia, and schistocytes on a blood smear, the latter causes acute kidney injury more frequently than TTP. In addition, gemcitabine-­induced TMA may not lead to severe decrease in ADAMTS13 activity. A kidney biopsy could confirm drug-induced TMA but was contraindicated in this case because of the thrombocytopenia. Gemcitabine should not be restarted if this side effect is suspected.

Given the continued rise in C difficile incidence, hospitalists should be aware that C difficile infection can cause extraintestinal illness.^9,10 Although uncommon, these extraintestinal complications are associated with high risk of mortality and frequently occur in those with a history of intestinal injury or inflammation and a concomitant bloodstream infection.¹⁰ Regarding the possibility of C difficile contributing to hemolysis in this case, the patient’s low blood counts and hemolysis improved concomitantly with more aggressive treatment of C difficile infection. Although his blood cultures were sterile, C difficile is notoriously difficult to culture. Prior case reports have associated C difficile with intravascular hemolysis, which leads to the possibility that the patient did have a very rare manifestation of this unfortunately common infection.¹¹

This case provides an excellent example of a diagnostic pivot point initiated by new information that fundamentally alters a patient’s diagnostic journey. Here, the finding of pyroipoikilocytes on peripheral smear led us to alter the differential diagnosis. Such pivots are often “surprises” that cause the care team to stop and reconsider their differential diagnosis because the problem representation has fundamentally changed. This patient’s unexpected fiery finding provided a pivot point that led to his effective treatment and recovery.

• In evaluating symptomatic cancer patients, providers must consider sequelae of the tumor, paraneoplastic phenomena, and treatment-related complications.
• Hemolytic anemia may represent a life-threatening emergency particularly when accompanied by AKI and requires urgent peripheral blood smear evaluation.
• Acquired pyropoikilocytosis is a specific finding known to be associated only with thermal injury, drug-induced TMA, and bacterial toxin–mediated hemolysis.

The authors have nothing to disclose.

A 62-year-old man with metastatic non–small cell lung cancer (NSCLC) presented to the Emergency Department with 3 days of progressive generalized weakness, anorexia, and nonbloody diarrhea. He denied fever, chills, nausea, vomiting, cough, shortness of breath, or abdominal pain. He had no sick contacts.

One diagnostic approach for patients with cancer who present with new symptoms is to consider diagnoses both related and unrelated to the cancer. Cancer-related diagnoses can include the broad categories of complications related to the tumor itself (such as mass effect), paraneoplastic phenomena, or treatment-related complications (such as infection from immunosuppression or chemotherapy toxicity).

For this patient with metastatic NSCLC, weakness, anorexia, and diarrhea are unlikely to be related to mass effect unless the patient has peritoneal metastases (an uncommon complication of NSCLC) with carcinomatosis-associated diarrhea.

Paraneoplastic phenomena, such as hypercalcemia or hyponatremia from the syndrome of inappropriate antidiuretic hormone (SIADH), are common with NSCLC and could both lead to weakness and anorexia. Hematologic consequences of NSCLC (or its treatment) include anemia, thrombosis, and thrombotic microangiopathy (TMA), though diarrhea, in the absence of abdominal pain or hematochezia, would be unexpected.

Weakness, anorexia, and diarrhea may also be symptoms of chemotherapy toxicity or an infection resulting from immunosuppression. It would be important to know what specific treatment the patient has received. Chemotherapy commonly causes neutropenia and predisposes to rapidly progressive infections, while immunotherapies have other toxicities. Diarrhea is a common toxicity of the checkpoint inhibitors and anaplastic lymphoma kinase (ALK) inhibitors that are frequently used to treat metastatic NSCLC. Checkpoint inhibitors also are known to cause a wide range of autoimmune phenomena including colitis.

Finally, the patient’s symptoms may be unrelated to the cancer. Weakness, anorexia, and nonbloody diarrhea could be signs of viral or bacterial gastroenteritis or Clostridioides difficile colitis particularly with frequent healthcare contact or antimicrobial use.

Two days prior, he had been diagnosed with nonsevere Clostridioides difficile colitis in an acute care clinic. He was started on oral metronidazole, but his diarrhea worsened over the next day and was accompanied by weakness and anorexia. Additional past medical history included untreated hepatitis C infection, chronic kidney disease stage 3, seizure disorder, and left lung NSCLC (adenocarcinoma). The lung cancer was diagnosed 8 months prior when he had presented with hemoptysis and 3 months of progressive constitutional symptoms. Imaging at that time revealed metastases to the contralateral lung and regional lymph nodes, as well as vertebrae, ribs, and pelvis. He had no abdominal metastases. He was initially treated with carboplatin and paclitaxel. After a partial response to initial chemotherapy, he developed peripheral neuropathy and was switched to gemcitabine 12 weeks ago. He received five cycles of gemcitabine over 10 weeks. He was last administered gemcitabine 2 weeks prior. He had not received any additional chemotherapy or immunotherapy. He had a 40 pack-year history of smoking, but quit when diagnosed with cancer. He did not drink alcohol. He had no recent travel or sick contacts. He was not on any medications. He was homeless but staying with family members in the area. Additional review of systems was negative for recent bleeding, bruising, hemoptysis, melena, hematochezia, or hematuria.

Recent treatment with gemcitabine could contribute to the presentation in a number of ways. First, gemcitabine is associated with myelosuppression and neutropenia that could predispose him to infectious colitis. Second, gemcitabine is known to cause anemia, anorexia, diarrhea, and fatigue. Third, gemcitabine may also cause renal injury that can contribute to worsening anemia. He may be at greater risk of anemia and renal toxicity because of preexisting chronic kidney disease. Finally, gemcitabine can rarely cause TMA with characteristics that mimic the hemolytic-uremic syndrome with microangiopathic hemolytic anemia, mild thrombocytopenia, and severe acute kidney injury (AKI).

In addition, worsening infectious colitis could certainly explain his presenting symptoms. At this point, local mass effect seems unlikely despite his metastatic disease. Lastly, it should be noted that, in an immunosuppressed cancer patient, multiple problems could be present at the same time. Laboratory testing should evaluate for hypercalcemia, SIADH, hematologic indexes, and renal function. If initial laboratory evaluation is unrevealing, abdominal imaging may be needed to assess for carcinomatosis, complications from colitis, typhlitis, abscess, or perforation.

On physical examination, the patient appeared fatigued. His temperature was 36.8°C, blood pressure 158/72 mm Hg, pulse 88 beats per minute, respiratory rate 16 breaths per minute, and oxygen saturation was 96% while breathing ambient air. There was neither scleral icterus nor conjunctival injection but he had mild conjunctival pallor. Cardiovascular and lung examinations were normal. Abdominal exam revealed normal bowel sounds without tenderness or organomegaly. He had no supraclavicular, axillary, or inguinal lymphadenopathy. He was alert and oriented. Cranial nerves II through XII were intact. He had decreased muscle bulk in his extremities without focal weakness. Gait and reflexes were not tested.

Initial laboratory testing revealed a white blood cell count of 5.5 K/mm³, hemoglobin of 5 g/dL (hemoglobin 1 month prior was 10.1 g/dL), and platelet count of 20 K/mm³ (platelet count 1 month prior was 246 K/mm³). Creatinine was 3.9 mg/dL (compared with a baseline of 1.8 mg/dL), and blood urea nitrogen was 39 mg/dL. His sodium was 137 mEq/L, potassium 4.2 mEq/L, chloride 105 mEq/L, bicarbonate 22 mEq/L, and thyroid stimulating hormone 0.9 mU/L. His total protein was 4.9 g/dL, albumin 2.1 g/dL, alkaline phosphatase 60 IU/L, alanine aminotransferase 17 IU/L, aspartate aminotransferase 60 IU/L, direct bilirubin 0.2 mg/dL, and total bilirubin 0.5 mg/dL. A chest x-ray showed no infiltrates.

The patient’s laboratory tests reveal several important new findings, including severe acute on chronic anemia, acute thrombocytopenia, and AKI, without clinical evidence of acute blood loss. These changes could be parts of a syndrome or multiple independent disorders. The most urgent priority is to evaluate for TMAs, many of which are fatal if not diagnosed and treated expeditiously. This includes thrombotic thrombocytopenic purpura (TTP), disseminated intravascular hemolysis (DIC), and atypical hemolytic uremic syndrome (aHUS). A manual review of a peripheral blood smear is required to evaluate for fragmented red blood cells (schistocytes). Thereafter, ancillary testing to confirm intravascular hemolysis would include measuring free plasma hemoglobin and lactate dehydrogenase (LDH). Additionally, in intravascular hemolysis, haptoglobin should be depleted and urinalysis should show heme-positive urine without RBCs. In this case the patient’s normal bilirubin studies argue against hemolysis; however, elevated bilirubin is variably present in hemolytic anemias depending on the liver’s ability to conjugate and excrete bilirubin, the relative degree of RBC turnover, and type of hemolysis. Patients with intravascular hemolysis lose hemoglobin directly into the urine leaving relatively little hemoglobin to be incorporated into bile once it has reached the reticuloendothelial system. This results in relatively normal bilirubin levels. More specific indicators of intravascular hemolysis include pink colored plasma on visual inspection (commonly done in the blood bank as part of assessing for hemolytic transfusion reactions), measuring plasma free hemoglobin, or by detecting hemoglobin in the urine.

If microangiopathic hemolytic anemia (MAHA) is excluded, then other causes of these laboratory abnormalities should be considered. Bleeding is the most common cause for anemia, and thrombocytopenia predisposes patients to bleeding. However, there is no evidence of bleeding in this patient, and such a rapid acute anemia is unlikely to be caused by occult blood loss alone. Concurrent anemia and thrombocytopenia could be evidence of bone marrow toxicity from chemotherapy or neoplastic infiltration. With marrow infiltration, there are typically signs on the peripheral smear of leukoerythroblastosis, with circulating nucleated red blood cells and early myeloid forms. Concurrent immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), or Evans’ Syndrome, should also be considered. AIHA would be suggested by spherocytes on the peripheral smear, elevated LDH and a positive direct antibody test (DAT).

Regarding the AKI, the patient has diarrhea, which could lead to prerenal azotemia and acute tubular necrosis. A formal urinalysis would evaluate for prerenal and intrinsic kidney disease. TMA can cause intrinsic kidney injury with a benign urinary sediment. The blood urea nitrogen-to-creatinine ratio is not elevated, but in a patient with malnutrition this may not indicate prerenal azotemia. In summary, to differentiate potential TMAs from other causes, the patient needs a blood smear, coagulation studies, and an evaluation for hemolysis, including a urinalysis for free heme and any evidence of intrinsic kidney disease.

Urinalysis showed amber-colored, dilute urine with no white blood cells, red blood cells, protein, or casts. It was positive for blood and negative for bilirubin and hemosiderin. LDH was 1,382 IU/L (reference range 135-225 IU/L), and haptoglobin was unmeasurably low. His ferritin was 2,267 ng/mL, serum iron was 57 mcg/dL, total iron-binding capacity was 241 mcg/dL, and transferrin was 162 mcg/dL. Reticulocyte count was 6% (reticulocyte index of 0.86). Vitamin B12 level was normal. DAT was negative; INR and aPTT were normal. Fibrinogen was 287 mg/dL (reference range 200-400 mg/dL), and D-dimer was 5,095 ng/mL (reference range 0-229 ng/mL).

The urinalysis shows no active sediment to suggest vasculitis or glomerulonephritis. The kidney injury could be the result of renal toxicity from free hemoglobin or as part of TMA caused by microvascular thrombosis. The dilute urine makes prerenal azotemia less likely.

There is clearly acute intravascular hemolysis occurring as evidenced by hemoglobinuria, very high LDH, and undetectable serum haptoglobin. The hemolysis is acute because chronic intravascular hemolysis would lead to positive urine hemosiderin via deposition in the renal tubules. Autoimmune hemolytic anemia is much less likely, but not ruled out, by a negative DAT.

This syndrome can be further refined from acute anemia to acute anemia with likely nonimmune intravascular hemolysis, acute thrombocytopenia, and AKI with hemoglobinuria and a bland urinary sediment. At this point, intravascular hemolysis and kidney injury could be part of a unifying diagnosis. However, this does not account for the patient’s thrombocytopenia, and TMA remains the best explanation for the constellation of findings. Review of the peripheral blood smear is urgent because evidence of MAHA would prompt urgent plasma exchange based on presumptive diagnosis of acquired TTP to later be confirmed with ADAMTS13 activity testing. Most TMAs are treated with supportive care only; TTP and aHUS have specific interventions that change the natural history of the disease (plasma exchange and anticomplement therapy, respectively). Given both the deadly natural history and opportunity to intervene with plasma exchange, patients with TMA should be treated with urgent plasma exchange until ADAMTS13 deficiency is confirmed or refuted. One TMA that can be excluded at this point is DIC. DIC in its acute and chronic forms nearly universally causes MAHA, thrombocytopenia, and consumptive coagulopathy including hypofibrinogenemia.

If MAHA is excluded, then other causes of intravascular hemolysis should be considered, along with causes of thrombocytopenia that might be occurring concurrently. Intravascular hemolysis can be further differentiated by etiologies primarily related to the RBC or whether the RBC is the innocent bystander amidst a systemic illness. RBC disorders include syndromes affecting RBC fragility like hereditary spherocytosis or RBC enzymopathies (G6PD deficiency), but these do not cause thrombocytopenia. One exception is an acquired membrane defect, paroxysmal nocturnal hemoglobinuria (PNH), in which RBCs and other blood cells become susceptible to complement-mediated lysis. Testing for PNH by peripheral blood flow cytometry should be considered if the blood film lacks schistocytes. Systemic disorders that cause intravascular hemolysis include severe burns (heat damage to RBCs), RBC trauma from “march hemoglobinuria” or mechanical heart valves, immune (antibody-mediated) hemolysis from Rh immune globulin administration, cold agglutinin disease or ABO mismatched transfusion, and infections including the intraerythrocyte parasites malaria, Bartonellosis, and Babesiosis, as well as organisms that induce RBC fragility such as Leishmaniasis, Clostridium perfringens, and Haemophilus influenzae B.

On review of additional history, the patient had not recently received blood products. He had received heparin during prior hospitalizations, but had no prior history of thrombosis. He had no history of tick exposure. Peripheral blood smear was obtained and reviewed by a hematopathologist. It showed no schistocytes or spherocytes, but demonstrated pyropoikilocytosis.

The blood smear helps narrow the differential further. The lack of schistocytes makes TMA far less likely and so plasma exchange is not urgently indicated. The differential still includes drug-­induced TMA (gemcitabine being a well-known cause for TMA) and cancer-associated TMA could still cause these findings, but plasma exchange does not improve outcomes. Acquired (immune) TTP is very unlikely unless the patient did not improve with supportive care or developed neurologic symptoms. Similarly, atypical (complement-driven) HUS would only be considered if renal failure did not improve with supportive care.

The blood smear does show a surprising finding of pyropoikilocytosis. Pyropoikilocytosis refers to changes in RBC shape (poikilocytosis) typically seen with thermal injury or rare RBC membrane structural defects. Hereditary pyropoikilocytosis, a very rare disease, is characterized by chronic hyperproliferative, compensated anemia, and occasional hemolytic crises. These crises are associated with splenomegaly, reticulocytosis, and elevated bilirubin with jaundice. As the patient has no history of similar episodes, the blood smear changes are not due to a hereditary cause and obviously not due to thermal injury (ie, severe burns). Pyropoikilocytosis has been rarely reported in drug-induced TMA and in severe bacterial bloodstream infections (most commonly Gram-negative bacilli). This patient has received gemcitabine (a known cause of drug-induced TMA) and has a recently diagnosed infection (C difficile colitis), either of which could be linked to this rare blood smear finding. Both of these syndromes would be treated with supportive care plus avoidance of future gemcitabine.

Transfusion of packed RBCs is indicated given his profound anemia and symptoms of fatigue. One should obtain further testing for cold agglutinins, PNH, and echocardiography to exclude endocarditis. If he were to become critically ill, anuric, or encephalopathic, then one could consider plasma exchange for treatment of TMA and hemoglobin-mediated AKI. Pyropoikilocytosis should be considered the result of drug-induced TMA, severe C difficile colitis, or an occult infection.

The patient was transfused packed RBCs. Because of a concern for an acute TMA such as TTP, both a hematopathologist and the consulting hematology/oncology team reviewed the peripheral blood morphology emergently. He was given aggressive fluid resuscitation and received 3 L of IV lactated ringers’ solution. An echocardiogram did not show valvular abnormalities. A renal biopsy was contraindicated because of the severe thrombocytopenia.

Given the recently confirmed C difficile colitis along with the findings of pyropoikilocytosis on the peripheral smear, toxin-mediated intravascular hemolysis from systemic C difficile infection became the leading diagnosis. Positing that the C difficile colitis was inadequately treated with oral metronidazole, aggressive treatment for C difficile was initiated with oral vancomycin in addition to intravenous metronidazole. Intravenous metronidazole was included given his elevated creatinine, presence of severe colitis on imaging, and concern he may be at risk for translocation of colonic C difficile or exotoxin into the bloodstream.

Over the course of the next 3 days, the patient’s platelet count normalized and his hemoglobin, creatinine, and symptoms of fatigue improved. Blood cultures remained negative. The patient’s rapid improvement with antibiotics supported our final diagnosis of toxin-mediated hemolysis caused by a systemic C difficile infection. On follow-up testing after hospital discharge, hemoglobin had returned to prior baseline and there was no recurrent hemolysis. Gemcitabine was considered to be a possible cause of his hemolytic anemia and was not continued in further treatment for his NSCLC.

When evaluating patients with cancer who present with fatigue, hospitalists should consider a broad list of potential causes. The differential should include etiologies directly related to the malignancy, paraneoplastic phenomena, treatment-related complications, and diseases unrelated to cancer. In addition, as the number of medications used for cancer proliferates, hospitalists must take a detailed history of the agents used and be aware of major side effects. Using this information, hospitalists may undertake a targeted approach to diagnostics while searching for a cause of fatigue.

When lab testing reveals profound anemia, hospitalists must consider syndromes that may require emergent management. Anemia can be caused by decreased RBC production, and acute anemia in the absence of clear blood loss suggests hemolysis. Moreover, the combination of elevated LDH and low haptoglobin is quite specific of hemolytic anemia.^1,2 Once hemolytic anemia is identified, DIC and TMA syndromes (such as TTP) need to be considered. The combination of hemolytic anemia and AKI may indicate a medical emergency and should prompt hospitalists to obtain an urgent peripheral blood smear to help narrow the differential.³

The absence of schistocytes on a blood smear does not rule out TTP or HUS, but does argue strongly against these diagnoses.^4,5 Of note, consultation with a hematopathologist and hematology subspecialist should be done to ensure appropriate and timely review of the peripheral blood smear.

In this case, the blood smear led to a very rare finding of pyropoikilocytosis. The unexpected result should prompt a broader review of the medical history particularly as it relates to the patient’s broader symptoms and laboratory abnormalities. Acquired pyropoikilocytosis is a very specific finding known to be associated only with hyperthermal injury (seen in burn patients), drug-induced TMA, and bacterial bloodstream infections, mainly Gram-negative toxins and Clostridioidal infections.^6-8 In this case, both drug-induced TMA and C difficile infection were considered.

Gemcitabine-induced TMA can occur with either short or long term use of the medication and can be difficult to distinguish from TTP. While both TTP and gemcitabine-induced TMA can cause thrombocytopenia, hemolytic anemia, and schistocytes on a blood smear, the latter causes acute kidney injury more frequently than TTP. In addition, gemcitabine-­induced TMA may not lead to severe decrease in ADAMTS13 activity. A kidney biopsy could confirm drug-induced TMA but was contraindicated in this case because of the thrombocytopenia. Gemcitabine should not be restarted if this side effect is suspected.

Given the continued rise in C difficile incidence, hospitalists should be aware that C difficile infection can cause extraintestinal illness.^9,10 Although uncommon, these extraintestinal complications are associated with high risk of mortality and frequently occur in those with a history of intestinal injury or inflammation and a concomitant bloodstream infection.¹⁰ Regarding the possibility of C difficile contributing to hemolysis in this case, the patient’s low blood counts and hemolysis improved concomitantly with more aggressive treatment of C difficile infection. Although his blood cultures were sterile, C difficile is notoriously difficult to culture. Prior case reports have associated C difficile with intravascular hemolysis, which leads to the possibility that the patient did have a very rare manifestation of this unfortunately common infection.¹¹

This case provides an excellent example of a diagnostic pivot point initiated by new information that fundamentally alters a patient’s diagnostic journey. Here, the finding of pyroipoikilocytes on peripheral smear led us to alter the differential diagnosis. Such pivots are often “surprises” that cause the care team to stop and reconsider their differential diagnosis because the problem representation has fundamentally changed. This patient’s unexpected fiery finding provided a pivot point that led to his effective treatment and recovery.

• In evaluating symptomatic cancer patients, providers must consider sequelae of the tumor, paraneoplastic phenomena, and treatment-related complications.
• Hemolytic anemia may represent a life-threatening emergency particularly when accompanied by AKI and requires urgent peripheral blood smear evaluation.
• Acquired pyropoikilocytosis is a specific finding known to be associated only with thermal injury, drug-induced TMA, and bacterial toxin–mediated hemolysis.

The authors have nothing to disclose.

A 62-year-old man with metastatic non–small cell lung cancer (NSCLC) presented to the Emergency Department with 3 days of progressive generalized weakness, anorexia, and nonbloody diarrhea. He denied fever, chills, nausea, vomiting, cough, shortness of breath, or abdominal pain. He had no sick contacts.

One diagnostic approach for patients with cancer who present with new symptoms is to consider diagnoses both related and unrelated to the cancer. Cancer-related diagnoses can include the broad categories of complications related to the tumor itself (such as mass effect), paraneoplastic phenomena, or treatment-related complications (such as infection from immunosuppression or chemotherapy toxicity).

For this patient with metastatic NSCLC, weakness, anorexia, and diarrhea are unlikely to be related to mass effect unless the patient has peritoneal metastases (an uncommon complication of NSCLC) with carcinomatosis-associated diarrhea.

Paraneoplastic phenomena, such as hypercalcemia or hyponatremia from the syndrome of inappropriate antidiuretic hormone (SIADH), are common with NSCLC and could both lead to weakness and anorexia. Hematologic consequences of NSCLC (or its treatment) include anemia, thrombosis, and thrombotic microangiopathy (TMA), though diarrhea, in the absence of abdominal pain or hematochezia, would be unexpected.

Weakness, anorexia, and diarrhea may also be symptoms of chemotherapy toxicity or an infection resulting from immunosuppression. It would be important to know what specific treatment the patient has received. Chemotherapy commonly causes neutropenia and predisposes to rapidly progressive infections, while immunotherapies have other toxicities. Diarrhea is a common toxicity of the checkpoint inhibitors and anaplastic lymphoma kinase (ALK) inhibitors that are frequently used to treat metastatic NSCLC. Checkpoint inhibitors also are known to cause a wide range of autoimmune phenomena including colitis.

Finally, the patient’s symptoms may be unrelated to the cancer. Weakness, anorexia, and nonbloody diarrhea could be signs of viral or bacterial gastroenteritis or Clostridioides difficile colitis particularly with frequent healthcare contact or antimicrobial use.

Two days prior, he had been diagnosed with nonsevere Clostridioides difficile colitis in an acute care clinic. He was started on oral metronidazole, but his diarrhea worsened over the next day and was accompanied by weakness and anorexia. Additional past medical history included untreated hepatitis C infection, chronic kidney disease stage 3, seizure disorder, and left lung NSCLC (adenocarcinoma). The lung cancer was diagnosed 8 months prior when he had presented with hemoptysis and 3 months of progressive constitutional symptoms. Imaging at that time revealed metastases to the contralateral lung and regional lymph nodes, as well as vertebrae, ribs, and pelvis. He had no abdominal metastases. He was initially treated with carboplatin and paclitaxel. After a partial response to initial chemotherapy, he developed peripheral neuropathy and was switched to gemcitabine 12 weeks ago. He received five cycles of gemcitabine over 10 weeks. He was last administered gemcitabine 2 weeks prior. He had not received any additional chemotherapy or immunotherapy. He had a 40 pack-year history of smoking, but quit when diagnosed with cancer. He did not drink alcohol. He had no recent travel or sick contacts. He was not on any medications. He was homeless but staying with family members in the area. Additional review of systems was negative for recent bleeding, bruising, hemoptysis, melena, hematochezia, or hematuria.

Recent treatment with gemcitabine could contribute to the presentation in a number of ways. First, gemcitabine is associated with myelosuppression and neutropenia that could predispose him to infectious colitis. Second, gemcitabine is known to cause anemia, anorexia, diarrhea, and fatigue. Third, gemcitabine may also cause renal injury that can contribute to worsening anemia. He may be at greater risk of anemia and renal toxicity because of preexisting chronic kidney disease. Finally, gemcitabine can rarely cause TMA with characteristics that mimic the hemolytic-uremic syndrome with microangiopathic hemolytic anemia, mild thrombocytopenia, and severe acute kidney injury (AKI).

In addition, worsening infectious colitis could certainly explain his presenting symptoms. At this point, local mass effect seems unlikely despite his metastatic disease. Lastly, it should be noted that, in an immunosuppressed cancer patient, multiple problems could be present at the same time. Laboratory testing should evaluate for hypercalcemia, SIADH, hematologic indexes, and renal function. If initial laboratory evaluation is unrevealing, abdominal imaging may be needed to assess for carcinomatosis, complications from colitis, typhlitis, abscess, or perforation.

On physical examination, the patient appeared fatigued. His temperature was 36.8°C, blood pressure 158/72 mm Hg, pulse 88 beats per minute, respiratory rate 16 breaths per minute, and oxygen saturation was 96% while breathing ambient air. There was neither scleral icterus nor conjunctival injection but he had mild conjunctival pallor. Cardiovascular and lung examinations were normal. Abdominal exam revealed normal bowel sounds without tenderness or organomegaly. He had no supraclavicular, axillary, or inguinal lymphadenopathy. He was alert and oriented. Cranial nerves II through XII were intact. He had decreased muscle bulk in his extremities without focal weakness. Gait and reflexes were not tested.

Initial laboratory testing revealed a white blood cell count of 5.5 K/mm³, hemoglobin of 5 g/dL (hemoglobin 1 month prior was 10.1 g/dL), and platelet count of 20 K/mm³ (platelet count 1 month prior was 246 K/mm³). Creatinine was 3.9 mg/dL (compared with a baseline of 1.8 mg/dL), and blood urea nitrogen was 39 mg/dL. His sodium was 137 mEq/L, potassium 4.2 mEq/L, chloride 105 mEq/L, bicarbonate 22 mEq/L, and thyroid stimulating hormone 0.9 mU/L. His total protein was 4.9 g/dL, albumin 2.1 g/dL, alkaline phosphatase 60 IU/L, alanine aminotransferase 17 IU/L, aspartate aminotransferase 60 IU/L, direct bilirubin 0.2 mg/dL, and total bilirubin 0.5 mg/dL. A chest x-ray showed no infiltrates.

The patient’s laboratory tests reveal several important new findings, including severe acute on chronic anemia, acute thrombocytopenia, and AKI, without clinical evidence of acute blood loss. These changes could be parts of a syndrome or multiple independent disorders. The most urgent priority is to evaluate for TMAs, many of which are fatal if not diagnosed and treated expeditiously. This includes thrombotic thrombocytopenic purpura (TTP), disseminated intravascular hemolysis (DIC), and atypical hemolytic uremic syndrome (aHUS). A manual review of a peripheral blood smear is required to evaluate for fragmented red blood cells (schistocytes). Thereafter, ancillary testing to confirm intravascular hemolysis would include measuring free plasma hemoglobin and lactate dehydrogenase (LDH). Additionally, in intravascular hemolysis, haptoglobin should be depleted and urinalysis should show heme-positive urine without RBCs. In this case the patient’s normal bilirubin studies argue against hemolysis; however, elevated bilirubin is variably present in hemolytic anemias depending on the liver’s ability to conjugate and excrete bilirubin, the relative degree of RBC turnover, and type of hemolysis. Patients with intravascular hemolysis lose hemoglobin directly into the urine leaving relatively little hemoglobin to be incorporated into bile once it has reached the reticuloendothelial system. This results in relatively normal bilirubin levels. More specific indicators of intravascular hemolysis include pink colored plasma on visual inspection (commonly done in the blood bank as part of assessing for hemolytic transfusion reactions), measuring plasma free hemoglobin, or by detecting hemoglobin in the urine.

If microangiopathic hemolytic anemia (MAHA) is excluded, then other causes of these laboratory abnormalities should be considered. Bleeding is the most common cause for anemia, and thrombocytopenia predisposes patients to bleeding. However, there is no evidence of bleeding in this patient, and such a rapid acute anemia is unlikely to be caused by occult blood loss alone. Concurrent anemia and thrombocytopenia could be evidence of bone marrow toxicity from chemotherapy or neoplastic infiltration. With marrow infiltration, there are typically signs on the peripheral smear of leukoerythroblastosis, with circulating nucleated red blood cells and early myeloid forms. Concurrent immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA), or Evans’ Syndrome, should also be considered. AIHA would be suggested by spherocytes on the peripheral smear, elevated LDH and a positive direct antibody test (DAT).

Regarding the AKI, the patient has diarrhea, which could lead to prerenal azotemia and acute tubular necrosis. A formal urinalysis would evaluate for prerenal and intrinsic kidney disease. TMA can cause intrinsic kidney injury with a benign urinary sediment. The blood urea nitrogen-to-creatinine ratio is not elevated, but in a patient with malnutrition this may not indicate prerenal azotemia. In summary, to differentiate potential TMAs from other causes, the patient needs a blood smear, coagulation studies, and an evaluation for hemolysis, including a urinalysis for free heme and any evidence of intrinsic kidney disease.

Urinalysis showed amber-colored, dilute urine with no white blood cells, red blood cells, protein, or casts. It was positive for blood and negative for bilirubin and hemosiderin. LDH was 1,382 IU/L (reference range 135-225 IU/L), and haptoglobin was unmeasurably low. His ferritin was 2,267 ng/mL, serum iron was 57 mcg/dL, total iron-binding capacity was 241 mcg/dL, and transferrin was 162 mcg/dL. Reticulocyte count was 6% (reticulocyte index of 0.86). Vitamin B12 level was normal. DAT was negative; INR and aPTT were normal. Fibrinogen was 287 mg/dL (reference range 200-400 mg/dL), and D-dimer was 5,095 ng/mL (reference range 0-229 ng/mL).

The urinalysis shows no active sediment to suggest vasculitis or glomerulonephritis. The kidney injury could be the result of renal toxicity from free hemoglobin or as part of TMA caused by microvascular thrombosis. The dilute urine makes prerenal azotemia less likely.

There is clearly acute intravascular hemolysis occurring as evidenced by hemoglobinuria, very high LDH, and undetectable serum haptoglobin. The hemolysis is acute because chronic intravascular hemolysis would lead to positive urine hemosiderin via deposition in the renal tubules. Autoimmune hemolytic anemia is much less likely, but not ruled out, by a negative DAT.

This syndrome can be further refined from acute anemia to acute anemia with likely nonimmune intravascular hemolysis, acute thrombocytopenia, and AKI with hemoglobinuria and a bland urinary sediment. At this point, intravascular hemolysis and kidney injury could be part of a unifying diagnosis. However, this does not account for the patient’s thrombocytopenia, and TMA remains the best explanation for the constellation of findings. Review of the peripheral blood smear is urgent because evidence of MAHA would prompt urgent plasma exchange based on presumptive diagnosis of acquired TTP to later be confirmed with ADAMTS13 activity testing. Most TMAs are treated with supportive care only; TTP and aHUS have specific interventions that change the natural history of the disease (plasma exchange and anticomplement therapy, respectively). Given both the deadly natural history and opportunity to intervene with plasma exchange, patients with TMA should be treated with urgent plasma exchange until ADAMTS13 deficiency is confirmed or refuted. One TMA that can be excluded at this point is DIC. DIC in its acute and chronic forms nearly universally causes MAHA, thrombocytopenia, and consumptive coagulopathy including hypofibrinogenemia.

If MAHA is excluded, then other causes of intravascular hemolysis should be considered, along with causes of thrombocytopenia that might be occurring concurrently. Intravascular hemolysis can be further differentiated by etiologies primarily related to the RBC or whether the RBC is the innocent bystander amidst a systemic illness. RBC disorders include syndromes affecting RBC fragility like hereditary spherocytosis or RBC enzymopathies (G6PD deficiency), but these do not cause thrombocytopenia. One exception is an acquired membrane defect, paroxysmal nocturnal hemoglobinuria (PNH), in which RBCs and other blood cells become susceptible to complement-mediated lysis. Testing for PNH by peripheral blood flow cytometry should be considered if the blood film lacks schistocytes. Systemic disorders that cause intravascular hemolysis include severe burns (heat damage to RBCs), RBC trauma from “march hemoglobinuria” or mechanical heart valves, immune (antibody-mediated) hemolysis from Rh immune globulin administration, cold agglutinin disease or ABO mismatched transfusion, and infections including the intraerythrocyte parasites malaria, Bartonellosis, and Babesiosis, as well as organisms that induce RBC fragility such as Leishmaniasis, Clostridium perfringens, and Haemophilus influenzae B.

On review of additional history, the patient had not recently received blood products. He had received heparin during prior hospitalizations, but had no prior history of thrombosis. He had no history of tick exposure. Peripheral blood smear was obtained and reviewed by a hematopathologist. It showed no schistocytes or spherocytes, but demonstrated pyropoikilocytosis.

The blood smear helps narrow the differential further. The lack of schistocytes makes TMA far less likely and so plasma exchange is not urgently indicated. The differential still includes drug-­induced TMA (gemcitabine being a well-known cause for TMA) and cancer-associated TMA could still cause these findings, but plasma exchange does not improve outcomes. Acquired (immune) TTP is very unlikely unless the patient did not improve with supportive care or developed neurologic symptoms. Similarly, atypical (complement-driven) HUS would only be considered if renal failure did not improve with supportive care.

The blood smear does show a surprising finding of pyropoikilocytosis. Pyropoikilocytosis refers to changes in RBC shape (poikilocytosis) typically seen with thermal injury or rare RBC membrane structural defects. Hereditary pyropoikilocytosis, a very rare disease, is characterized by chronic hyperproliferative, compensated anemia, and occasional hemolytic crises. These crises are associated with splenomegaly, reticulocytosis, and elevated bilirubin with jaundice. As the patient has no history of similar episodes, the blood smear changes are not due to a hereditary cause and obviously not due to thermal injury (ie, severe burns). Pyropoikilocytosis has been rarely reported in drug-induced TMA and in severe bacterial bloodstream infections (most commonly Gram-negative bacilli). This patient has received gemcitabine (a known cause of drug-induced TMA) and has a recently diagnosed infection (C difficile colitis), either of which could be linked to this rare blood smear finding. Both of these syndromes would be treated with supportive care plus avoidance of future gemcitabine.

Transfusion of packed RBCs is indicated given his profound anemia and symptoms of fatigue. One should obtain further testing for cold agglutinins, PNH, and echocardiography to exclude endocarditis. If he were to become critically ill, anuric, or encephalopathic, then one could consider plasma exchange for treatment of TMA and hemoglobin-mediated AKI. Pyropoikilocytosis should be considered the result of drug-induced TMA, severe C difficile colitis, or an occult infection.

The patient was transfused packed RBCs. Because of a concern for an acute TMA such as TTP, both a hematopathologist and the consulting hematology/oncology team reviewed the peripheral blood morphology emergently. He was given aggressive fluid resuscitation and received 3 L of IV lactated ringers’ solution. An echocardiogram did not show valvular abnormalities. A renal biopsy was contraindicated because of the severe thrombocytopenia.

Given the recently confirmed C difficile colitis along with the findings of pyropoikilocytosis on the peripheral smear, toxin-mediated intravascular hemolysis from systemic C difficile infection became the leading diagnosis. Positing that the C difficile colitis was inadequately treated with oral metronidazole, aggressive treatment for C difficile was initiated with oral vancomycin in addition to intravenous metronidazole. Intravenous metronidazole was included given his elevated creatinine, presence of severe colitis on imaging, and concern he may be at risk for translocation of colonic C difficile or exotoxin into the bloodstream.

Over the course of the next 3 days, the patient’s platelet count normalized and his hemoglobin, creatinine, and symptoms of fatigue improved. Blood cultures remained negative. The patient’s rapid improvement with antibiotics supported our final diagnosis of toxin-mediated hemolysis caused by a systemic C difficile infection. On follow-up testing after hospital discharge, hemoglobin had returned to prior baseline and there was no recurrent hemolysis. Gemcitabine was considered to be a possible cause of his hemolytic anemia and was not continued in further treatment for his NSCLC.

When evaluating patients with cancer who present with fatigue, hospitalists should consider a broad list of potential causes. The differential should include etiologies directly related to the malignancy, paraneoplastic phenomena, treatment-related complications, and diseases unrelated to cancer. In addition, as the number of medications used for cancer proliferates, hospitalists must take a detailed history of the agents used and be aware of major side effects. Using this information, hospitalists may undertake a targeted approach to diagnostics while searching for a cause of fatigue.

When lab testing reveals profound anemia, hospitalists must consider syndromes that may require emergent management. Anemia can be caused by decreased RBC production, and acute anemia in the absence of clear blood loss suggests hemolysis. Moreover, the combination of elevated LDH and low haptoglobin is quite specific of hemolytic anemia.^1,2 Once hemolytic anemia is identified, DIC and TMA syndromes (such as TTP) need to be considered. The combination of hemolytic anemia and AKI may indicate a medical emergency and should prompt hospitalists to obtain an urgent peripheral blood smear to help narrow the differential.³

The absence of schistocytes on a blood smear does not rule out TTP or HUS, but does argue strongly against these diagnoses.^4,5 Of note, consultation with a hematopathologist and hematology subspecialist should be done to ensure appropriate and timely review of the peripheral blood smear.

In this case, the blood smear led to a very rare finding of pyropoikilocytosis. The unexpected result should prompt a broader review of the medical history particularly as it relates to the patient’s broader symptoms and laboratory abnormalities. Acquired pyropoikilocytosis is a very specific finding known to be associated only with hyperthermal injury (seen in burn patients), drug-induced TMA, and bacterial bloodstream infections, mainly Gram-negative toxins and Clostridioidal infections.^6-8 In this case, both drug-induced TMA and C difficile infection were considered.

Gemcitabine-induced TMA can occur with either short or long term use of the medication and can be difficult to distinguish from TTP. While both TTP and gemcitabine-induced TMA can cause thrombocytopenia, hemolytic anemia, and schistocytes on a blood smear, the latter causes acute kidney injury more frequently than TTP. In addition, gemcitabine-­induced TMA may not lead to severe decrease in ADAMTS13 activity. A kidney biopsy could confirm drug-induced TMA but was contraindicated in this case because of the thrombocytopenia. Gemcitabine should not be restarted if this side effect is suspected.

Given the continued rise in C difficile incidence, hospitalists should be aware that C difficile infection can cause extraintestinal illness.^9,10 Although uncommon, these extraintestinal complications are associated with high risk of mortality and frequently occur in those with a history of intestinal injury or inflammation and a concomitant bloodstream infection.¹⁰ Regarding the possibility of C difficile contributing to hemolysis in this case, the patient’s low blood counts and hemolysis improved concomitantly with more aggressive treatment of C difficile infection. Although his blood cultures were sterile, C difficile is notoriously difficult to culture. Prior case reports have associated C difficile with intravascular hemolysis, which leads to the possibility that the patient did have a very rare manifestation of this unfortunately common infection.¹¹

This case provides an excellent example of a diagnostic pivot point initiated by new information that fundamentally alters a patient’s diagnostic journey. Here, the finding of pyroipoikilocytes on peripheral smear led us to alter the differential diagnosis. Such pivots are often “surprises” that cause the care team to stop and reconsider their differential diagnosis because the problem representation has fundamentally changed. This patient’s unexpected fiery finding provided a pivot point that led to his effective treatment and recovery.

• In evaluating symptomatic cancer patients, providers must consider sequelae of the tumor, paraneoplastic phenomena, and treatment-related complications.
• Hemolytic anemia may represent a life-threatening emergency particularly when accompanied by AKI and requires urgent peripheral blood smear evaluation.
• Acquired pyropoikilocytosis is a specific finding known to be associated only with thermal injury, drug-induced TMA, and bacterial toxin–mediated hemolysis.

The authors have nothing to disclose.

More than 200 million patients worldwide undergo major noncardiac surgery each year. Of these, more than 10 million patients suffer a major adverse cardiovascular event (MACE) within 30 days of surgery.¹ Elevated troponins after noncardiac surgery have been associated with increased mortality, but the management of these patients and the indications for screening remain unclear. The nomenclature around myocardial injury also remains confusing. In this Progress Note, we aim to define myocardial injury after noncardiac surgery (MINS) and discuss the key questions on MINS and postoperative troponin elevation.

A PubMed search for medical subject headings and the terms “myocardial injury after noncardiac surgery,” “perioperative troponin,” and “postoperative troponin” restricted to humans, English language, and published in the past 5 years resulted in 144 articles. Articles most relevant to this progress note were included. Guidelines from major societies on perioperative cardiovascular assessment and management were also reviewed.

The Fourth Universal Definition of Myocardial Infarction ( UDMI 4) defines myocardial injury as detection of an elevated cardiac troponin above the 99th percentile upper reference limit (URL).² Different troponin assays are not comparable and institutions set their own thresholds for abnormal troponin. Per UDMI 4, myocardial injury is classified as (Figure)^2-4:

• Acute Myocardial Infarction (MI): This is defined as “detection of a rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile URL and ≥1 of the following: symptoms of acute myocardial ischemia, new ischemic electrocardiographic changes, development of pathological Q waves, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.” If these patients have an acute atherosclerotic plaque rupture, they are classified as Type 1 MI (T1MI), and if they have a mismatch between oxygen supply/demand, they are classified as Type 2 MI (T2MI).
• Acute Nonischemic Myocardial Injury (NIMI): This is defined as detection of both a rise and/or fall of cardiac troponin and one or more cardiac troponin values above the 99th percentile URL, but no overt clinical evidence of myocardial ischemia.
• Chronic Myocardial Injury: This is defined as one or more cardiac troponin values above the 99th percentile URL but without a rise and/or fall pattern.

MINS is defined as a rise and/or fall of cardiac biomarkers of presumed ischemic etiology within 30 days of noncardiac surgery that may occur with or without the clinical criteria necessary to fulfill the universal definition of MI (Figure).^5-8

A meta-analysis of 169 studies reported the overall incidence of MINS to be 17.9%; the incidence was 19.6% when systematic troponin screening was done versus 9.9% when troponins were ordered selectively based on the clinical context.⁵

That meta-analysis found that patients with MINS were more likely to be older, male, undergoing nonelective surgeries, and have hypertension, coronary artery disease (CAD), prior MI, heart failure, or kidney disease.⁵ Intraoperative hypotension (defined as systolic blood pressure <100 mm Hg or mean arterial pressure <55 mm Hg for up to 5 minutes or <60 mm Hg for 30 minutes or more) and intraoperative tachycardia (defined as heart rate >100 beats per minute) have been associated with MINS.^5,9 The relationship between anesthesia type and MINS is uncertain.

MINS is associated with an increased risk of 30-day mortality, nonfatal cardiac arrest, heart failure, and stroke.In the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) studies, the majority of patients did not have ischemic symptoms.^6,7 In this study, 30-day mortality rates were 8.5% to 13.5% in patients with ischemic symptoms or electrocardiographic changes and 2.9% to 7.7% in patients with asymptomatic troponin elevations. Among the patients without MINS, 30-day mortality was 0.6% to 1.1%. Higher levels of cardiac troponin were associated with higher mortality rates and shorter time to death.

The recommendations for perioperative screening for MINS vary from society to society. Although MINS is associated with worse outcomes, and most patients with MINS are asymptomatic, perioperative screening for MINS in the absence of clinical signs or symptoms is currently not recommended by the American College of Cardiology/American Heart Association (ACC/AHA).¹⁰

ACC/AHA

“The usefulness of postoperative screening with troponin levels in patients at high risk for perioperative MI, but without signs or symptoms suggestive of myocardial ischemia or MI, is uncertain in the absence of established risks and benefits of a defined management strategy (Class IIb; level of evidence [LOE]–B).”¹⁰

European Society of Cardiology

“Measurement of B-type natriuretic peptides (BNP) and high-sensitivity troponins (hsTn) after surgery may be considered in high-risk patients to improve risk stratification (Class IIb; LOE-B). Preoperatively and postoperatively, patients who could most benefit from BNP or hsTn measurements are those with metabolic equivalents (METs) ≤4 or those with a revised cardiac risk index (RCRI) score >1 for vascular surgery and >2 for nonvascular surgery. Postoperatively, patients with a surgical Apgar score <7 should also be monitored with BNP or hsTn to detect complications early, independent of their RCRI values.”¹¹

Canadian Cardiovascular Society

“We recommend obtaining daily troponins for 48-72 hours after noncardiac surgery in patients with a baseline risk of >5% for cardiovascular death or nonfatal MI at 30 days after surgery (ie, patients with an elevated N-terminal-proBNP (NT-proBNP)/BNP before surgery or, if there is no NT-proBNP/BNP before surgery, in those who have an RCRI score ≥1, age 45-64 years with significant cardiovascular disease, or age ≥65 years) (Strong recommendation; Moderate quality evidence).”¹

Currently, evidence-based therapies are well established only for T1MI. However, it is often challenging to differentiate T1MI from other causes of troponin elevation in the perioperative setting in which anesthesia, sedation, or analgesia may mask ischemic symptoms that typically prompt further investigation. While peak troponin levels may be higher in T1MI than they are in T2MI, the initial or delta change in the troponin may provide poor discrimination between T1MI and T2MI.² Management is complicated not only by the uncertainty about the underlying diagnosis (T1MI, T2MI, or NIMI) but also by the heterogeneity in the underlying pathophysiology of troponin elevation in patients with T2MI and NIMI. Patients with T2MI are generally sicker and have higher mortality than patients with T1MI, and management typically involves treating the underlying reason for oxygen supply/demand mismatch. Mortality in T2MI is more commonly caused by noncardiovascular causes, but underlying CAD is an independent predictor of cardiovascular death or recurrent MI in these patients.

The MANAGE trial (Management of Myocardial Injury After Noncardiac Surgery) had several methodological limitations to inform clinical practice but showed potential benefit of dabigatran in patients with MINS.¹² In this trial, patients on dabigatran had significantly lower rates of the primary efficacy outcome (composite of vascular mortality and nonfatal MI, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism) without a significant increase in life-threatening, major, or critical organ bleeding. Of the secondary efficacy outcomes, only nonhemorrhagic stroke was significantly reduced with dabigatran, but the event rate was low. In the subgroup analysis, patients randomized to dabigatran within 5 days of MINS and those meeting the criteria for MI had significantly lower rates of the primary efficacy outcome.

Patients with T2MI with known CAD may benefit from long-term risk reduction strategies for secondary prevention. There are no definitive management strategies in the literature for T2MI with unknown or no CAD. The SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapy) enrolled 9,136 patients with MI with nonobstructive coronary arteries (MINOCA).¹³ Though MINOCA may include T1MI patients, the majority of these patients are classified as T2MI under UDMI 4. Therefore, it has been proposed that data from this registry may inform management on T2MI.¹⁴ Data from this registry showed that statins and angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers were associated with lower incidence of MACE over a mean follow-up of 4.1 years. Dual-antiplatelet therapy or beta blockers did not significantly lower the incidence of MACE.¹³ In another study assessing 2-year mortality in patients with T2MI, beta blockers were beneficial.¹⁵

Who should be screened?

Screening can be performed if further risk stratification of high-risk patients or patients with poor functional status is desired. European Society of Cardiology and Canadian Cardiovascular Society guidelines provide guidance on the screening criteria. Troponin elevation in a low-risk group is associated with a low mortality rate, and many of these troponin elevations may be secondary to causes other than myocardial ischemia.

How should screening be conducted?

If planning to obtain postoperative troponins, then preoperative troponin should be obtained because 35% of the patients may have a chronic troponin elevation.

What is the risk if postoperative troponin screening is not performed?

Most patients with MINS are asymptomatic. Systematic screening with troponins (compared with selective screening based on clinical signs or symptoms) can detect T1MI that would otherwise remain occult and undiagnosed.

What is the risk if postoperative troponin screening is performed?

Detecting asymptomatic troponin elevations could lead to potentially harmful treatments (eg, increased risk of bleeding with antithrombotics in the postoperative setting, increased use of cardiac angiography, or addition of new medications such as statins and beta-blockers in the postoperative setting with the potential for adverse effects).

How should MINS be documented?

ST-elevation and non–ST elevation MI (STEMI and NSTEMI) should be reserved for T1MI only. T1MI should be documented when acute plaque rupture is strongly suspected. T2MI should be documented when oxygen supply/demand mismatch is strongly suspected as the etiology of acute MI (eg, T2MI secondary to tachyarrhythmia, hypertensive emergency, or septic shock). Documenting as “demand ischemia” or “unlikely acute coronary syndrome” for T2MI or NIMI should be avoided. Troponin elevations not meeting the criteria for acute MI should be documented as “non-MI troponin elevation” (eg, non-MI troponin elevation secondary to chronic kidney disease or left ventricular hypertrophy). Terms like “troponinitis” or “troponinemia” should be avoided.³

Can MINS be prevented?

There are no well-defined strategies for prevention of MINS, but cardiovascular risk factors should be optimized preoperatively for all patients. In a meta-analysis, preoperative aspirin was not associated with reduced incidence of MINS, and the role of preoperative statins remains speculative; however, nonacute initiation of beta-blockers preoperatively was associated with a lower incidence of MINS.⁵ Withholding angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers in the 24 hours prior to surgery has been associated with a lower incidence of MINS. Intraoperative hypotension or tachycardia should be avoided.

While MINS has been associated with increased 30-day mortality, there are currently no definitive evidence-based management strategies for these patients. Institutions should consider creating decision-support tools if considering screening for MINS based on patient- and surgery-specific risk factors.

The authors have nothing to disclose.

More than 200 million patients worldwide undergo major noncardiac surgery each year. Of these, more than 10 million patients suffer a major adverse cardiovascular event (MACE) within 30 days of surgery.¹ Elevated troponins after noncardiac surgery have been associated with increased mortality, but the management of these patients and the indications for screening remain unclear. The nomenclature around myocardial injury also remains confusing. In this Progress Note, we aim to define myocardial injury after noncardiac surgery (MINS) and discuss the key questions on MINS and postoperative troponin elevation.

A PubMed search for medical subject headings and the terms “myocardial injury after noncardiac surgery,” “perioperative troponin,” and “postoperative troponin” restricted to humans, English language, and published in the past 5 years resulted in 144 articles. Articles most relevant to this progress note were included. Guidelines from major societies on perioperative cardiovascular assessment and management were also reviewed.

The Fourth Universal Definition of Myocardial Infarction ( UDMI 4) defines myocardial injury as detection of an elevated cardiac troponin above the 99th percentile upper reference limit (URL).² Different troponin assays are not comparable and institutions set their own thresholds for abnormal troponin. Per UDMI 4, myocardial injury is classified as (Figure)^2-4:

• Acute Myocardial Infarction (MI): This is defined as “detection of a rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile URL and ≥1 of the following: symptoms of acute myocardial ischemia, new ischemic electrocardiographic changes, development of pathological Q waves, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.” If these patients have an acute atherosclerotic plaque rupture, they are classified as Type 1 MI (T1MI), and if they have a mismatch between oxygen supply/demand, they are classified as Type 2 MI (T2MI).
• Acute Nonischemic Myocardial Injury (NIMI): This is defined as detection of both a rise and/or fall of cardiac troponin and one or more cardiac troponin values above the 99th percentile URL, but no overt clinical evidence of myocardial ischemia.
• Chronic Myocardial Injury: This is defined as one or more cardiac troponin values above the 99th percentile URL but without a rise and/or fall pattern.

MINS is defined as a rise and/or fall of cardiac biomarkers of presumed ischemic etiology within 30 days of noncardiac surgery that may occur with or without the clinical criteria necessary to fulfill the universal definition of MI (Figure).^5-8

A meta-analysis of 169 studies reported the overall incidence of MINS to be 17.9%; the incidence was 19.6% when systematic troponin screening was done versus 9.9% when troponins were ordered selectively based on the clinical context.⁵

That meta-analysis found that patients with MINS were more likely to be older, male, undergoing nonelective surgeries, and have hypertension, coronary artery disease (CAD), prior MI, heart failure, or kidney disease.⁵ Intraoperative hypotension (defined as systolic blood pressure <100 mm Hg or mean arterial pressure <55 mm Hg for up to 5 minutes or <60 mm Hg for 30 minutes or more) and intraoperative tachycardia (defined as heart rate >100 beats per minute) have been associated with MINS.^5,9 The relationship between anesthesia type and MINS is uncertain.

MINS is associated with an increased risk of 30-day mortality, nonfatal cardiac arrest, heart failure, and stroke.In the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) studies, the majority of patients did not have ischemic symptoms.^6,7 In this study, 30-day mortality rates were 8.5% to 13.5% in patients with ischemic symptoms or electrocardiographic changes and 2.9% to 7.7% in patients with asymptomatic troponin elevations. Among the patients without MINS, 30-day mortality was 0.6% to 1.1%. Higher levels of cardiac troponin were associated with higher mortality rates and shorter time to death.

The recommendations for perioperative screening for MINS vary from society to society. Although MINS is associated with worse outcomes, and most patients with MINS are asymptomatic, perioperative screening for MINS in the absence of clinical signs or symptoms is currently not recommended by the American College of Cardiology/American Heart Association (ACC/AHA).¹⁰

ACC/AHA

“The usefulness of postoperative screening with troponin levels in patients at high risk for perioperative MI, but without signs or symptoms suggestive of myocardial ischemia or MI, is uncertain in the absence of established risks and benefits of a defined management strategy (Class IIb; level of evidence [LOE]–B).”¹⁰

European Society of Cardiology

“Measurement of B-type natriuretic peptides (BNP) and high-sensitivity troponins (hsTn) after surgery may be considered in high-risk patients to improve risk stratification (Class IIb; LOE-B). Preoperatively and postoperatively, patients who could most benefit from BNP or hsTn measurements are those with metabolic equivalents (METs) ≤4 or those with a revised cardiac risk index (RCRI) score >1 for vascular surgery and >2 for nonvascular surgery. Postoperatively, patients with a surgical Apgar score <7 should also be monitored with BNP or hsTn to detect complications early, independent of their RCRI values.”¹¹

Canadian Cardiovascular Society

“We recommend obtaining daily troponins for 48-72 hours after noncardiac surgery in patients with a baseline risk of >5% for cardiovascular death or nonfatal MI at 30 days after surgery (ie, patients with an elevated N-terminal-proBNP (NT-proBNP)/BNP before surgery or, if there is no NT-proBNP/BNP before surgery, in those who have an RCRI score ≥1, age 45-64 years with significant cardiovascular disease, or age ≥65 years) (Strong recommendation; Moderate quality evidence).”¹

Currently, evidence-based therapies are well established only for T1MI. However, it is often challenging to differentiate T1MI from other causes of troponin elevation in the perioperative setting in which anesthesia, sedation, or analgesia may mask ischemic symptoms that typically prompt further investigation. While peak troponin levels may be higher in T1MI than they are in T2MI, the initial or delta change in the troponin may provide poor discrimination between T1MI and T2MI.² Management is complicated not only by the uncertainty about the underlying diagnosis (T1MI, T2MI, or NIMI) but also by the heterogeneity in the underlying pathophysiology of troponin elevation in patients with T2MI and NIMI. Patients with T2MI are generally sicker and have higher mortality than patients with T1MI, and management typically involves treating the underlying reason for oxygen supply/demand mismatch. Mortality in T2MI is more commonly caused by noncardiovascular causes, but underlying CAD is an independent predictor of cardiovascular death or recurrent MI in these patients.

The MANAGE trial (Management of Myocardial Injury After Noncardiac Surgery) had several methodological limitations to inform clinical practice but showed potential benefit of dabigatran in patients with MINS.¹² In this trial, patients on dabigatran had significantly lower rates of the primary efficacy outcome (composite of vascular mortality and nonfatal MI, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism) without a significant increase in life-threatening, major, or critical organ bleeding. Of the secondary efficacy outcomes, only nonhemorrhagic stroke was significantly reduced with dabigatran, but the event rate was low. In the subgroup analysis, patients randomized to dabigatran within 5 days of MINS and those meeting the criteria for MI had significantly lower rates of the primary efficacy outcome.

Patients with T2MI with known CAD may benefit from long-term risk reduction strategies for secondary prevention. There are no definitive management strategies in the literature for T2MI with unknown or no CAD. The SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapy) enrolled 9,136 patients with MI with nonobstructive coronary arteries (MINOCA).¹³ Though MINOCA may include T1MI patients, the majority of these patients are classified as T2MI under UDMI 4. Therefore, it has been proposed that data from this registry may inform management on T2MI.¹⁴ Data from this registry showed that statins and angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers were associated with lower incidence of MACE over a mean follow-up of 4.1 years. Dual-antiplatelet therapy or beta blockers did not significantly lower the incidence of MACE.¹³ In another study assessing 2-year mortality in patients with T2MI, beta blockers were beneficial.¹⁵

Who should be screened?

Screening can be performed if further risk stratification of high-risk patients or patients with poor functional status is desired. European Society of Cardiology and Canadian Cardiovascular Society guidelines provide guidance on the screening criteria. Troponin elevation in a low-risk group is associated with a low mortality rate, and many of these troponin elevations may be secondary to causes other than myocardial ischemia.

How should screening be conducted?

If planning to obtain postoperative troponins, then preoperative troponin should be obtained because 35% of the patients may have a chronic troponin elevation.

What is the risk if postoperative troponin screening is not performed?

Most patients with MINS are asymptomatic. Systematic screening with troponins (compared with selective screening based on clinical signs or symptoms) can detect T1MI that would otherwise remain occult and undiagnosed.

What is the risk if postoperative troponin screening is performed?

Detecting asymptomatic troponin elevations could lead to potentially harmful treatments (eg, increased risk of bleeding with antithrombotics in the postoperative setting, increased use of cardiac angiography, or addition of new medications such as statins and beta-blockers in the postoperative setting with the potential for adverse effects).

How should MINS be documented?

ST-elevation and non–ST elevation MI (STEMI and NSTEMI) should be reserved for T1MI only. T1MI should be documented when acute plaque rupture is strongly suspected. T2MI should be documented when oxygen supply/demand mismatch is strongly suspected as the etiology of acute MI (eg, T2MI secondary to tachyarrhythmia, hypertensive emergency, or septic shock). Documenting as “demand ischemia” or “unlikely acute coronary syndrome” for T2MI or NIMI should be avoided. Troponin elevations not meeting the criteria for acute MI should be documented as “non-MI troponin elevation” (eg, non-MI troponin elevation secondary to chronic kidney disease or left ventricular hypertrophy). Terms like “troponinitis” or “troponinemia” should be avoided.³

Can MINS be prevented?

There are no well-defined strategies for prevention of MINS, but cardiovascular risk factors should be optimized preoperatively for all patients. In a meta-analysis, preoperative aspirin was not associated with reduced incidence of MINS, and the role of preoperative statins remains speculative; however, nonacute initiation of beta-blockers preoperatively was associated with a lower incidence of MINS.⁵ Withholding angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers in the 24 hours prior to surgery has been associated with a lower incidence of MINS. Intraoperative hypotension or tachycardia should be avoided.

While MINS has been associated with increased 30-day mortality, there are currently no definitive evidence-based management strategies for these patients. Institutions should consider creating decision-support tools if considering screening for MINS based on patient- and surgery-specific risk factors.

The authors have nothing to disclose.

More than 200 million patients worldwide undergo major noncardiac surgery each year. Of these, more than 10 million patients suffer a major adverse cardiovascular event (MACE) within 30 days of surgery.¹ Elevated troponins after noncardiac surgery have been associated with increased mortality, but the management of these patients and the indications for screening remain unclear. The nomenclature around myocardial injury also remains confusing. In this Progress Note, we aim to define myocardial injury after noncardiac surgery (MINS) and discuss the key questions on MINS and postoperative troponin elevation.

A PubMed search for medical subject headings and the terms “myocardial injury after noncardiac surgery,” “perioperative troponin,” and “postoperative troponin” restricted to humans, English language, and published in the past 5 years resulted in 144 articles. Articles most relevant to this progress note were included. Guidelines from major societies on perioperative cardiovascular assessment and management were also reviewed.

The Fourth Universal Definition of Myocardial Infarction ( UDMI 4) defines myocardial injury as detection of an elevated cardiac troponin above the 99th percentile upper reference limit (URL).² Different troponin assays are not comparable and institutions set their own thresholds for abnormal troponin. Per UDMI 4, myocardial injury is classified as (Figure)^2-4:

• Acute Myocardial Infarction (MI): This is defined as “detection of a rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile URL and ≥1 of the following: symptoms of acute myocardial ischemia, new ischemic electrocardiographic changes, development of pathological Q waves, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.” If these patients have an acute atherosclerotic plaque rupture, they are classified as Type 1 MI (T1MI), and if they have a mismatch between oxygen supply/demand, they are classified as Type 2 MI (T2MI).
• Acute Nonischemic Myocardial Injury (NIMI): This is defined as detection of both a rise and/or fall of cardiac troponin and one or more cardiac troponin values above the 99th percentile URL, but no overt clinical evidence of myocardial ischemia.
• Chronic Myocardial Injury: This is defined as one or more cardiac troponin values above the 99th percentile URL but without a rise and/or fall pattern.

MINS is defined as a rise and/or fall of cardiac biomarkers of presumed ischemic etiology within 30 days of noncardiac surgery that may occur with or without the clinical criteria necessary to fulfill the universal definition of MI (Figure).^5-8

A meta-analysis of 169 studies reported the overall incidence of MINS to be 17.9%; the incidence was 19.6% when systematic troponin screening was done versus 9.9% when troponins were ordered selectively based on the clinical context.⁵

That meta-analysis found that patients with MINS were more likely to be older, male, undergoing nonelective surgeries, and have hypertension, coronary artery disease (CAD), prior MI, heart failure, or kidney disease.⁵ Intraoperative hypotension (defined as systolic blood pressure <100 mm Hg or mean arterial pressure <55 mm Hg for up to 5 minutes or <60 mm Hg for 30 minutes or more) and intraoperative tachycardia (defined as heart rate >100 beats per minute) have been associated with MINS.^5,9 The relationship between anesthesia type and MINS is uncertain.

MINS is associated with an increased risk of 30-day mortality, nonfatal cardiac arrest, heart failure, and stroke.In the Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) studies, the majority of patients did not have ischemic symptoms.^6,7 In this study, 30-day mortality rates were 8.5% to 13.5% in patients with ischemic symptoms or electrocardiographic changes and 2.9% to 7.7% in patients with asymptomatic troponin elevations. Among the patients without MINS, 30-day mortality was 0.6% to 1.1%. Higher levels of cardiac troponin were associated with higher mortality rates and shorter time to death.

The recommendations for perioperative screening for MINS vary from society to society. Although MINS is associated with worse outcomes, and most patients with MINS are asymptomatic, perioperative screening for MINS in the absence of clinical signs or symptoms is currently not recommended by the American College of Cardiology/American Heart Association (ACC/AHA).¹⁰

ACC/AHA

“The usefulness of postoperative screening with troponin levels in patients at high risk for perioperative MI, but without signs or symptoms suggestive of myocardial ischemia or MI, is uncertain in the absence of established risks and benefits of a defined management strategy (Class IIb; level of evidence [LOE]–B).”¹⁰

European Society of Cardiology

“Measurement of B-type natriuretic peptides (BNP) and high-sensitivity troponins (hsTn) after surgery may be considered in high-risk patients to improve risk stratification (Class IIb; LOE-B). Preoperatively and postoperatively, patients who could most benefit from BNP or hsTn measurements are those with metabolic equivalents (METs) ≤4 or those with a revised cardiac risk index (RCRI) score >1 for vascular surgery and >2 for nonvascular surgery. Postoperatively, patients with a surgical Apgar score <7 should also be monitored with BNP or hsTn to detect complications early, independent of their RCRI values.”¹¹

Canadian Cardiovascular Society

“We recommend obtaining daily troponins for 48-72 hours after noncardiac surgery in patients with a baseline risk of >5% for cardiovascular death or nonfatal MI at 30 days after surgery (ie, patients with an elevated N-terminal-proBNP (NT-proBNP)/BNP before surgery or, if there is no NT-proBNP/BNP before surgery, in those who have an RCRI score ≥1, age 45-64 years with significant cardiovascular disease, or age ≥65 years) (Strong recommendation; Moderate quality evidence).”¹

Currently, evidence-based therapies are well established only for T1MI. However, it is often challenging to differentiate T1MI from other causes of troponin elevation in the perioperative setting in which anesthesia, sedation, or analgesia may mask ischemic symptoms that typically prompt further investigation. While peak troponin levels may be higher in T1MI than they are in T2MI, the initial or delta change in the troponin may provide poor discrimination between T1MI and T2MI.² Management is complicated not only by the uncertainty about the underlying diagnosis (T1MI, T2MI, or NIMI) but also by the heterogeneity in the underlying pathophysiology of troponin elevation in patients with T2MI and NIMI. Patients with T2MI are generally sicker and have higher mortality than patients with T1MI, and management typically involves treating the underlying reason for oxygen supply/demand mismatch. Mortality in T2MI is more commonly caused by noncardiovascular causes, but underlying CAD is an independent predictor of cardiovascular death or recurrent MI in these patients.

The MANAGE trial (Management of Myocardial Injury After Noncardiac Surgery) had several methodological limitations to inform clinical practice but showed potential benefit of dabigatran in patients with MINS.¹² In this trial, patients on dabigatran had significantly lower rates of the primary efficacy outcome (composite of vascular mortality and nonfatal MI, nonhemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism) without a significant increase in life-threatening, major, or critical organ bleeding. Of the secondary efficacy outcomes, only nonhemorrhagic stroke was significantly reduced with dabigatran, but the event rate was low. In the subgroup analysis, patients randomized to dabigatran within 5 days of MINS and those meeting the criteria for MI had significantly lower rates of the primary efficacy outcome.

Patients with T2MI with known CAD may benefit from long-term risk reduction strategies for secondary prevention. There are no definitive management strategies in the literature for T2MI with unknown or no CAD. The SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapy) enrolled 9,136 patients with MI with nonobstructive coronary arteries (MINOCA).¹³ Though MINOCA may include T1MI patients, the majority of these patients are classified as T2MI under UDMI 4. Therefore, it has been proposed that data from this registry may inform management on T2MI.¹⁴ Data from this registry showed that statins and angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers were associated with lower incidence of MACE over a mean follow-up of 4.1 years. Dual-antiplatelet therapy or beta blockers did not significantly lower the incidence of MACE.¹³ In another study assessing 2-year mortality in patients with T2MI, beta blockers were beneficial.¹⁵

Who should be screened?

Screening can be performed if further risk stratification of high-risk patients or patients with poor functional status is desired. European Society of Cardiology and Canadian Cardiovascular Society guidelines provide guidance on the screening criteria. Troponin elevation in a low-risk group is associated with a low mortality rate, and many of these troponin elevations may be secondary to causes other than myocardial ischemia.

How should screening be conducted?

If planning to obtain postoperative troponins, then preoperative troponin should be obtained because 35% of the patients may have a chronic troponin elevation.

What is the risk if postoperative troponin screening is not performed?

Most patients with MINS are asymptomatic. Systematic screening with troponins (compared with selective screening based on clinical signs or symptoms) can detect T1MI that would otherwise remain occult and undiagnosed.

What is the risk if postoperative troponin screening is performed?

Detecting asymptomatic troponin elevations could lead to potentially harmful treatments (eg, increased risk of bleeding with antithrombotics in the postoperative setting, increased use of cardiac angiography, or addition of new medications such as statins and beta-blockers in the postoperative setting with the potential for adverse effects).

How should MINS be documented?

ST-elevation and non–ST elevation MI (STEMI and NSTEMI) should be reserved for T1MI only. T1MI should be documented when acute plaque rupture is strongly suspected. T2MI should be documented when oxygen supply/demand mismatch is strongly suspected as the etiology of acute MI (eg, T2MI secondary to tachyarrhythmia, hypertensive emergency, or septic shock). Documenting as “demand ischemia” or “unlikely acute coronary syndrome” for T2MI or NIMI should be avoided. Troponin elevations not meeting the criteria for acute MI should be documented as “non-MI troponin elevation” (eg, non-MI troponin elevation secondary to chronic kidney disease or left ventricular hypertrophy). Terms like “troponinitis” or “troponinemia” should be avoided.³

Can MINS be prevented?

There are no well-defined strategies for prevention of MINS, but cardiovascular risk factors should be optimized preoperatively for all patients. In a meta-analysis, preoperative aspirin was not associated with reduced incidence of MINS, and the role of preoperative statins remains speculative; however, nonacute initiation of beta-blockers preoperatively was associated with a lower incidence of MINS.⁵ Withholding angiotensin-­converting enzyme inhibitors or angiotensin II receptor blockers in the 24 hours prior to surgery has been associated with a lower incidence of MINS. Intraoperative hypotension or tachycardia should be avoided.

While MINS has been associated with increased 30-day mortality, there are currently no definitive evidence-based management strategies for these patients. Institutions should consider creating decision-support tools if considering screening for MINS based on patient- and surgery-specific risk factors.

The authors have nothing to disclose.