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Fecal transfer could be the transplant of youth
Fecal matter may be in the fountain of youth
Yes, you read that headline correctly. New research by scientists at Quadram Institute and the University of East Anglia, both in Norwich, England, supports the claim that transferring fecal microbes might actually have some positive effects on reversing the aging process in the eyes, brain, and gut.
How do they know? Mice, of course. In the study, scientists took the gut microbes from older mice and transferred them into the younger mince. The young mice displayed inflamed signs of aging in their guts, brains, and eyes, which, we all know, decline in function as we age. What happens is a chronic inflammation of cells as we get older that can be found in the brain or gut that leads to a degenerative state over time.
When the older mice received the gut microbes from younger mice, the investigators saw the reverse: Gut, brain, and eye functionality improved. In a way, minimizing the inflammation.
There’s tons of research out there that suggests gut health is the key to a healthy life, but this study points directly to an improvement in brain and vision functionality as a result of the transfer.
Now, we’re not insinuating you get a poo transfer as you reach old age. And the shift to human studies on microbiota replacement therapy is still in the works. But this definitely is a topic to watch and could be a game changer in the age-old quest to bottle youth or at least improve quality of life as we age.
For now, the scientists did find some connections between the beneficial bacteria in the transplants and the human diet that could have similar effects, like changes in the metabolism of certain fats and vitamin that could have effects on the inflammatory cells in the eye and brain.
The more you know!
It’s not lying, it’s preemptive truth
Lying is bad. Bold statement, we know, but a true one. After all, God spent an entire commandment telling people not to do the whole bearing false witness thing, and God is generally known for not joking around. He’s a pretty serious dude.
In case you’ve been wandering around the desert for a while and haven’t had wifi, we have a bit of a misinformation problem these days. People lie all the time about a lot of things, and a lot of people believe the lies. According to new research, however, there are also a lot of people who recognize the lies but accept them anyway because they believe that the lies will become true in the future.
Imagine the following scenario: A friend gets a job he’s not qualified for because he listed a skill he doesn’t have. That’s bad, right? And the people the researchers interviewed agreed, at least initially. But when informed that our friend is planning on obtaining the skill in summer classes in the near future, the study participants became far more willing to excuse the initial lie.
A friend jumping the gun on training he doesn’t have yet is fairly innocuous as far as lying goes, but as the researchers found, this willingness to forgive lies because they could become true extends far further. For example, millions of people do not vote illegally in U.S. elections, nor do White people get approved for mortgages at rates 300% higher than minorities, but when asked to imagine scenarios in which those statements could be true, study participants were less likely to condemn the lie and prevent it from spreading further, especially if their political viewpoints aligned with the respective falsehood.
It seems, then, that while we may aspire to not tell lies, we take after another guy with magic powers who spent too much time in the desert: “What I told you was true, from a certain point of view.”
It tastes like feng shui, but it’s not
You know about biomes. You’ve read about various microbiomes. Allow us to introduce you to the envirome,
The envirome “includes all the natural and man-made elements of our environment throughout the lifespan, notably the built environment,” said Robert Schneider, dean of the College of Integrative Medicine at Maharishi International University. Located in – you guessed it – Fairfield, Iowa, and home of the Fighting Transcendentalists. MAHARISHI RULES!
[Editor’s note: You made that up, right? Well, it really is in Iowa, but they don’t seem to have an athletic program.]
In an effort to maximize the envirome’s potential to improve quality of life, Dr. Schneider and his associates systematically integrated the principles of Maharishi Vastu architecture (MVA) into a comprehensive building system. MVA is “a holistic wellness architectural system that aligns buildings with nature’s intelligence, creating balanced, orderly, and integrated living environments with the goal of improving occupants’ lives,” the university explained in a written statement.
Since “modern medicine now recognizes the powerful effects of the ‘envirome’ on health,” Dr. Schneider said in that statement, the researchers reviewed 40 years’ worth of published studies on MVA’s benefits – an analysis that appears in Global Advances in Health and Medicine.
As far as our homes are concerned, here are some of the things MVA says we should be doing:
- The headboard of a bed should be oriented to the east or south when you sleep. This will improve mental health.
- While sitting at a desk or work area, a person should face east or north to improve brain coherence.
- The main entrance of a house should face east because morning light is superior to afternoon light.
And you were worried about feng shui. Well, forget feng shui. Feng shui is for amateurs. MVA is the way to go. MVA is the GOAT. MAHARISHI RULES!
Fecal matter may be in the fountain of youth
Yes, you read that headline correctly. New research by scientists at Quadram Institute and the University of East Anglia, both in Norwich, England, supports the claim that transferring fecal microbes might actually have some positive effects on reversing the aging process in the eyes, brain, and gut.
How do they know? Mice, of course. In the study, scientists took the gut microbes from older mice and transferred them into the younger mince. The young mice displayed inflamed signs of aging in their guts, brains, and eyes, which, we all know, decline in function as we age. What happens is a chronic inflammation of cells as we get older that can be found in the brain or gut that leads to a degenerative state over time.
When the older mice received the gut microbes from younger mice, the investigators saw the reverse: Gut, brain, and eye functionality improved. In a way, minimizing the inflammation.
There’s tons of research out there that suggests gut health is the key to a healthy life, but this study points directly to an improvement in brain and vision functionality as a result of the transfer.
Now, we’re not insinuating you get a poo transfer as you reach old age. And the shift to human studies on microbiota replacement therapy is still in the works. But this definitely is a topic to watch and could be a game changer in the age-old quest to bottle youth or at least improve quality of life as we age.
For now, the scientists did find some connections between the beneficial bacteria in the transplants and the human diet that could have similar effects, like changes in the metabolism of certain fats and vitamin that could have effects on the inflammatory cells in the eye and brain.
The more you know!
It’s not lying, it’s preemptive truth
Lying is bad. Bold statement, we know, but a true one. After all, God spent an entire commandment telling people not to do the whole bearing false witness thing, and God is generally known for not joking around. He’s a pretty serious dude.
In case you’ve been wandering around the desert for a while and haven’t had wifi, we have a bit of a misinformation problem these days. People lie all the time about a lot of things, and a lot of people believe the lies. According to new research, however, there are also a lot of people who recognize the lies but accept them anyway because they believe that the lies will become true in the future.
Imagine the following scenario: A friend gets a job he’s not qualified for because he listed a skill he doesn’t have. That’s bad, right? And the people the researchers interviewed agreed, at least initially. But when informed that our friend is planning on obtaining the skill in summer classes in the near future, the study participants became far more willing to excuse the initial lie.
A friend jumping the gun on training he doesn’t have yet is fairly innocuous as far as lying goes, but as the researchers found, this willingness to forgive lies because they could become true extends far further. For example, millions of people do not vote illegally in U.S. elections, nor do White people get approved for mortgages at rates 300% higher than minorities, but when asked to imagine scenarios in which those statements could be true, study participants were less likely to condemn the lie and prevent it from spreading further, especially if their political viewpoints aligned with the respective falsehood.
It seems, then, that while we may aspire to not tell lies, we take after another guy with magic powers who spent too much time in the desert: “What I told you was true, from a certain point of view.”
It tastes like feng shui, but it’s not
You know about biomes. You’ve read about various microbiomes. Allow us to introduce you to the envirome,
The envirome “includes all the natural and man-made elements of our environment throughout the lifespan, notably the built environment,” said Robert Schneider, dean of the College of Integrative Medicine at Maharishi International University. Located in – you guessed it – Fairfield, Iowa, and home of the Fighting Transcendentalists. MAHARISHI RULES!
[Editor’s note: You made that up, right? Well, it really is in Iowa, but they don’t seem to have an athletic program.]
In an effort to maximize the envirome’s potential to improve quality of life, Dr. Schneider and his associates systematically integrated the principles of Maharishi Vastu architecture (MVA) into a comprehensive building system. MVA is “a holistic wellness architectural system that aligns buildings with nature’s intelligence, creating balanced, orderly, and integrated living environments with the goal of improving occupants’ lives,” the university explained in a written statement.
Since “modern medicine now recognizes the powerful effects of the ‘envirome’ on health,” Dr. Schneider said in that statement, the researchers reviewed 40 years’ worth of published studies on MVA’s benefits – an analysis that appears in Global Advances in Health and Medicine.
As far as our homes are concerned, here are some of the things MVA says we should be doing:
- The headboard of a bed should be oriented to the east or south when you sleep. This will improve mental health.
- While sitting at a desk or work area, a person should face east or north to improve brain coherence.
- The main entrance of a house should face east because morning light is superior to afternoon light.
And you were worried about feng shui. Well, forget feng shui. Feng shui is for amateurs. MVA is the way to go. MVA is the GOAT. MAHARISHI RULES!
Fecal matter may be in the fountain of youth
Yes, you read that headline correctly. New research by scientists at Quadram Institute and the University of East Anglia, both in Norwich, England, supports the claim that transferring fecal microbes might actually have some positive effects on reversing the aging process in the eyes, brain, and gut.
How do they know? Mice, of course. In the study, scientists took the gut microbes from older mice and transferred them into the younger mince. The young mice displayed inflamed signs of aging in their guts, brains, and eyes, which, we all know, decline in function as we age. What happens is a chronic inflammation of cells as we get older that can be found in the brain or gut that leads to a degenerative state over time.
When the older mice received the gut microbes from younger mice, the investigators saw the reverse: Gut, brain, and eye functionality improved. In a way, minimizing the inflammation.
There’s tons of research out there that suggests gut health is the key to a healthy life, but this study points directly to an improvement in brain and vision functionality as a result of the transfer.
Now, we’re not insinuating you get a poo transfer as you reach old age. And the shift to human studies on microbiota replacement therapy is still in the works. But this definitely is a topic to watch and could be a game changer in the age-old quest to bottle youth or at least improve quality of life as we age.
For now, the scientists did find some connections between the beneficial bacteria in the transplants and the human diet that could have similar effects, like changes in the metabolism of certain fats and vitamin that could have effects on the inflammatory cells in the eye and brain.
The more you know!
It’s not lying, it’s preemptive truth
Lying is bad. Bold statement, we know, but a true one. After all, God spent an entire commandment telling people not to do the whole bearing false witness thing, and God is generally known for not joking around. He’s a pretty serious dude.
In case you’ve been wandering around the desert for a while and haven’t had wifi, we have a bit of a misinformation problem these days. People lie all the time about a lot of things, and a lot of people believe the lies. According to new research, however, there are also a lot of people who recognize the lies but accept them anyway because they believe that the lies will become true in the future.
Imagine the following scenario: A friend gets a job he’s not qualified for because he listed a skill he doesn’t have. That’s bad, right? And the people the researchers interviewed agreed, at least initially. But when informed that our friend is planning on obtaining the skill in summer classes in the near future, the study participants became far more willing to excuse the initial lie.
A friend jumping the gun on training he doesn’t have yet is fairly innocuous as far as lying goes, but as the researchers found, this willingness to forgive lies because they could become true extends far further. For example, millions of people do not vote illegally in U.S. elections, nor do White people get approved for mortgages at rates 300% higher than minorities, but when asked to imagine scenarios in which those statements could be true, study participants were less likely to condemn the lie and prevent it from spreading further, especially if their political viewpoints aligned with the respective falsehood.
It seems, then, that while we may aspire to not tell lies, we take after another guy with magic powers who spent too much time in the desert: “What I told you was true, from a certain point of view.”
It tastes like feng shui, but it’s not
You know about biomes. You’ve read about various microbiomes. Allow us to introduce you to the envirome,
The envirome “includes all the natural and man-made elements of our environment throughout the lifespan, notably the built environment,” said Robert Schneider, dean of the College of Integrative Medicine at Maharishi International University. Located in – you guessed it – Fairfield, Iowa, and home of the Fighting Transcendentalists. MAHARISHI RULES!
[Editor’s note: You made that up, right? Well, it really is in Iowa, but they don’t seem to have an athletic program.]
In an effort to maximize the envirome’s potential to improve quality of life, Dr. Schneider and his associates systematically integrated the principles of Maharishi Vastu architecture (MVA) into a comprehensive building system. MVA is “a holistic wellness architectural system that aligns buildings with nature’s intelligence, creating balanced, orderly, and integrated living environments with the goal of improving occupants’ lives,” the university explained in a written statement.
Since “modern medicine now recognizes the powerful effects of the ‘envirome’ on health,” Dr. Schneider said in that statement, the researchers reviewed 40 years’ worth of published studies on MVA’s benefits – an analysis that appears in Global Advances in Health and Medicine.
As far as our homes are concerned, here are some of the things MVA says we should be doing:
- The headboard of a bed should be oriented to the east or south when you sleep. This will improve mental health.
- While sitting at a desk or work area, a person should face east or north to improve brain coherence.
- The main entrance of a house should face east because morning light is superior to afternoon light.
And you were worried about feng shui. Well, forget feng shui. Feng shui is for amateurs. MVA is the way to go. MVA is the GOAT. MAHARISHI RULES!
Surgery handoffs still a risky juncture in care – but increasing communication can help
It involved a 70-year-old man who had a history of prostate cancer, obstructive sleep apnea, and hernias. In January, he had a surgery for hernia repair. On the 3rd day after the procedure, he was transferred to the hospital medicine service at about 9 p.m. and was on a patient-controlled pump for pain and had abdominal drains. Because of the extensive surgery and because he had begun to walk shortly after the procedure, he wasn’t on thrombosis prevention medication, Dr. Merli explained at the annual meeting of the American College of Physicians.
The day after his transfer he was walking with a physical therapist when he became short of breath, his oxygen saturation dropped, and his heart rate soared. Bilateral pulmonary emboli were found, along with thrombosis in the right leg.
What was remarkable, Dr. Merli noted, was what the patient’s medical record was lacking.
He added, “I think if we start looking at this at our sites, we may find out that communication needs to be improved, and I believe standardized.”
This situation underscores the continuing need to refine handoffs between surgery and hospital medicine, a point in care that is primed for potential errors, the other panelists noted during the session.
Most important information is often not communicated
A 2010 study in pediatrics that looked at intern-to-intern handoffs found that the most important piece of information wasn’t communicated successfully 60% of the time – in other words, more often than not, the person on the receiving end didn’t really understand that crucial part of the scenario. Since then, the literature has been regularly populated with studies attempting to refine handoff procedures.
Lily Ackermann, MD, hospitalist and clinical associate professor of medicine at Jefferson, said in the session that hospitalists need to be sure to reach out to surgery at important junctures in care.
“I would say the No. 1 biggest mistake we make is not calling the surgery attending directly when clinical questions arise,” she said. “I think this is very important – attending [physician in hospital medicine] to attending [physician in surgery].”
Murray Cohen, MD, director of acute care surgery at Jefferson, said he shared that concern.
“We want to be called, we want to be called for our patients,” he said in the session. “And we’re upset when you don’t call for our patients.”
Hospitalists should discuss blood loss, pain management, management of drains, deep vein thrombosis prevention, nutrition, infectious disease concerns, and timing of vaccines post procedure, Dr. Ackermann said during the presentation,
The panelists also emphasized that understanding the follow-up care that surgery was planning after a procedure is important, and to not just expect surgeons to actively follow a patient. They also reminded hospitalists to look at the wounds and make sure they understand how to handle the wounds going forward. Plus, when transferring a patient to surgery, hospitalists should understand when getting someone to surgery is urgent and not to order unnecessary tests as a formality when time is of the essence, they said.
IPASS: a formalized handoff process
The panelists all spoke highly of a formalized handoff process known as IPASS. This acronym reminds physicians to ask specific questions.
The I represents illness severity and calls for asking: “Is the patient stable or unstable?
The P stands for patient summary and is meant to prompt physicians to seek details about the procedure.
The A is for action list, which is meant to remind the physician to get the post-op plan for neurological, cardiovascular, gastrointestinal, and other areas.
The first S is for situational awareness, and calls for asking: What is the biggest concern over the next 24 hours?
The final S represents synthesis by the receiver, prompting a physician to summarize the information he or she has received about the patient.
Natalie Margules, MD, a clinical instructor and hospitalist at Jefferson who did not present in the session, reiterated the value of the IPASS system. Before it was used for handoffs, she said, “I was never taught anything formalized – basically, just ‘Tell them what’s important.’
Dr. Margules noted that she considers the framework’s call for the synthesis to be one of it most useful parts.
Dr. Merli, Dr. Ackermann, and Dr. Cohen reported no relevant financial disclosures.
It involved a 70-year-old man who had a history of prostate cancer, obstructive sleep apnea, and hernias. In January, he had a surgery for hernia repair. On the 3rd day after the procedure, he was transferred to the hospital medicine service at about 9 p.m. and was on a patient-controlled pump for pain and had abdominal drains. Because of the extensive surgery and because he had begun to walk shortly after the procedure, he wasn’t on thrombosis prevention medication, Dr. Merli explained at the annual meeting of the American College of Physicians.
The day after his transfer he was walking with a physical therapist when he became short of breath, his oxygen saturation dropped, and his heart rate soared. Bilateral pulmonary emboli were found, along with thrombosis in the right leg.
What was remarkable, Dr. Merli noted, was what the patient’s medical record was lacking.
He added, “I think if we start looking at this at our sites, we may find out that communication needs to be improved, and I believe standardized.”
This situation underscores the continuing need to refine handoffs between surgery and hospital medicine, a point in care that is primed for potential errors, the other panelists noted during the session.
Most important information is often not communicated
A 2010 study in pediatrics that looked at intern-to-intern handoffs found that the most important piece of information wasn’t communicated successfully 60% of the time – in other words, more often than not, the person on the receiving end didn’t really understand that crucial part of the scenario. Since then, the literature has been regularly populated with studies attempting to refine handoff procedures.
Lily Ackermann, MD, hospitalist and clinical associate professor of medicine at Jefferson, said in the session that hospitalists need to be sure to reach out to surgery at important junctures in care.
“I would say the No. 1 biggest mistake we make is not calling the surgery attending directly when clinical questions arise,” she said. “I think this is very important – attending [physician in hospital medicine] to attending [physician in surgery].”
Murray Cohen, MD, director of acute care surgery at Jefferson, said he shared that concern.
“We want to be called, we want to be called for our patients,” he said in the session. “And we’re upset when you don’t call for our patients.”
Hospitalists should discuss blood loss, pain management, management of drains, deep vein thrombosis prevention, nutrition, infectious disease concerns, and timing of vaccines post procedure, Dr. Ackermann said during the presentation,
The panelists also emphasized that understanding the follow-up care that surgery was planning after a procedure is important, and to not just expect surgeons to actively follow a patient. They also reminded hospitalists to look at the wounds and make sure they understand how to handle the wounds going forward. Plus, when transferring a patient to surgery, hospitalists should understand when getting someone to surgery is urgent and not to order unnecessary tests as a formality when time is of the essence, they said.
IPASS: a formalized handoff process
The panelists all spoke highly of a formalized handoff process known as IPASS. This acronym reminds physicians to ask specific questions.
The I represents illness severity and calls for asking: “Is the patient stable or unstable?
The P stands for patient summary and is meant to prompt physicians to seek details about the procedure.
The A is for action list, which is meant to remind the physician to get the post-op plan for neurological, cardiovascular, gastrointestinal, and other areas.
The first S is for situational awareness, and calls for asking: What is the biggest concern over the next 24 hours?
The final S represents synthesis by the receiver, prompting a physician to summarize the information he or she has received about the patient.
Natalie Margules, MD, a clinical instructor and hospitalist at Jefferson who did not present in the session, reiterated the value of the IPASS system. Before it was used for handoffs, she said, “I was never taught anything formalized – basically, just ‘Tell them what’s important.’
Dr. Margules noted that she considers the framework’s call for the synthesis to be one of it most useful parts.
Dr. Merli, Dr. Ackermann, and Dr. Cohen reported no relevant financial disclosures.
It involved a 70-year-old man who had a history of prostate cancer, obstructive sleep apnea, and hernias. In January, he had a surgery for hernia repair. On the 3rd day after the procedure, he was transferred to the hospital medicine service at about 9 p.m. and was on a patient-controlled pump for pain and had abdominal drains. Because of the extensive surgery and because he had begun to walk shortly after the procedure, he wasn’t on thrombosis prevention medication, Dr. Merli explained at the annual meeting of the American College of Physicians.
The day after his transfer he was walking with a physical therapist when he became short of breath, his oxygen saturation dropped, and his heart rate soared. Bilateral pulmonary emboli were found, along with thrombosis in the right leg.
What was remarkable, Dr. Merli noted, was what the patient’s medical record was lacking.
He added, “I think if we start looking at this at our sites, we may find out that communication needs to be improved, and I believe standardized.”
This situation underscores the continuing need to refine handoffs between surgery and hospital medicine, a point in care that is primed for potential errors, the other panelists noted during the session.
Most important information is often not communicated
A 2010 study in pediatrics that looked at intern-to-intern handoffs found that the most important piece of information wasn’t communicated successfully 60% of the time – in other words, more often than not, the person on the receiving end didn’t really understand that crucial part of the scenario. Since then, the literature has been regularly populated with studies attempting to refine handoff procedures.
Lily Ackermann, MD, hospitalist and clinical associate professor of medicine at Jefferson, said in the session that hospitalists need to be sure to reach out to surgery at important junctures in care.
“I would say the No. 1 biggest mistake we make is not calling the surgery attending directly when clinical questions arise,” she said. “I think this is very important – attending [physician in hospital medicine] to attending [physician in surgery].”
Murray Cohen, MD, director of acute care surgery at Jefferson, said he shared that concern.
“We want to be called, we want to be called for our patients,” he said in the session. “And we’re upset when you don’t call for our patients.”
Hospitalists should discuss blood loss, pain management, management of drains, deep vein thrombosis prevention, nutrition, infectious disease concerns, and timing of vaccines post procedure, Dr. Ackermann said during the presentation,
The panelists also emphasized that understanding the follow-up care that surgery was planning after a procedure is important, and to not just expect surgeons to actively follow a patient. They also reminded hospitalists to look at the wounds and make sure they understand how to handle the wounds going forward. Plus, when transferring a patient to surgery, hospitalists should understand when getting someone to surgery is urgent and not to order unnecessary tests as a formality when time is of the essence, they said.
IPASS: a formalized handoff process
The panelists all spoke highly of a formalized handoff process known as IPASS. This acronym reminds physicians to ask specific questions.
The I represents illness severity and calls for asking: “Is the patient stable or unstable?
The P stands for patient summary and is meant to prompt physicians to seek details about the procedure.
The A is for action list, which is meant to remind the physician to get the post-op plan for neurological, cardiovascular, gastrointestinal, and other areas.
The first S is for situational awareness, and calls for asking: What is the biggest concern over the next 24 hours?
The final S represents synthesis by the receiver, prompting a physician to summarize the information he or she has received about the patient.
Natalie Margules, MD, a clinical instructor and hospitalist at Jefferson who did not present in the session, reiterated the value of the IPASS system. Before it was used for handoffs, she said, “I was never taught anything formalized – basically, just ‘Tell them what’s important.’
Dr. Margules noted that she considers the framework’s call for the synthesis to be one of it most useful parts.
Dr. Merli, Dr. Ackermann, and Dr. Cohen reported no relevant financial disclosures.
AT INTERNAL MEDICINE 2022
Omicron sublineages evade immunity from past infection
A South African study based on blood samples found that the BA.4 and BA.5 sublineages of Omicron were more likely to evade antibodies produced by previous Omicron infections than the immunity provided by vaccinations.
Scientists took blood samples from 39 people infected with Omicron, with 24 people not vaccinated and 15 vaccinated with the Pfizer or the Johnson & Johnson vaccines, Reuters reported.
“The vaccinated group showed about a fivefold higher neutralization capacity ... and should be better protected,” the investigators found, according to Reuters.
There was an eightfold decrease in antibody protection in unvaccinated blood samples when exposed to the subvariants compared to a threefold decrease in the blood samples from vaccinated people.
“Based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave,” the investigators found.
The finding is important because health authorities say cases caused by the sublineages are increasing in South Africa to a degree that the nation may be entering a fifth wave of COVID, Reuters said.
Health Minister Joe Phaahla said recently that hospitalizations were increasing but that ICU admissions had not greatly gone up yet.
A version of this article first appeared on WebMD.com.
A South African study based on blood samples found that the BA.4 and BA.5 sublineages of Omicron were more likely to evade antibodies produced by previous Omicron infections than the immunity provided by vaccinations.
Scientists took blood samples from 39 people infected with Omicron, with 24 people not vaccinated and 15 vaccinated with the Pfizer or the Johnson & Johnson vaccines, Reuters reported.
“The vaccinated group showed about a fivefold higher neutralization capacity ... and should be better protected,” the investigators found, according to Reuters.
There was an eightfold decrease in antibody protection in unvaccinated blood samples when exposed to the subvariants compared to a threefold decrease in the blood samples from vaccinated people.
“Based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave,” the investigators found.
The finding is important because health authorities say cases caused by the sublineages are increasing in South Africa to a degree that the nation may be entering a fifth wave of COVID, Reuters said.
Health Minister Joe Phaahla said recently that hospitalizations were increasing but that ICU admissions had not greatly gone up yet.
A version of this article first appeared on WebMD.com.
A South African study based on blood samples found that the BA.4 and BA.5 sublineages of Omicron were more likely to evade antibodies produced by previous Omicron infections than the immunity provided by vaccinations.
Scientists took blood samples from 39 people infected with Omicron, with 24 people not vaccinated and 15 vaccinated with the Pfizer or the Johnson & Johnson vaccines, Reuters reported.
“The vaccinated group showed about a fivefold higher neutralization capacity ... and should be better protected,” the investigators found, according to Reuters.
There was an eightfold decrease in antibody protection in unvaccinated blood samples when exposed to the subvariants compared to a threefold decrease in the blood samples from vaccinated people.
“Based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave,” the investigators found.
The finding is important because health authorities say cases caused by the sublineages are increasing in South Africa to a degree that the nation may be entering a fifth wave of COVID, Reuters said.
Health Minister Joe Phaahla said recently that hospitalizations were increasing but that ICU admissions had not greatly gone up yet.
A version of this article first appeared on WebMD.com.
Newly defined liver disorder associated with COVID mortality
People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.
A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.
Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.
“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”
The study was published in Hepatology Communications.
More evidence for clinical relevance of MAFLD
The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.
NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.
“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”
In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.
Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.
The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
Sorting COVID outcomes by liver steatosis
To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.
They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.
The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.
The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).
They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.
The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).
The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).
For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)
Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.
That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
Next steps and new questions
Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.
The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.
“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.
Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.
Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”
The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.
Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.
A version of this article first appeared on Medscape.com.
People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.
A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.
Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.
“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”
The study was published in Hepatology Communications.
More evidence for clinical relevance of MAFLD
The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.
NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.
“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”
In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.
Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.
The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
Sorting COVID outcomes by liver steatosis
To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.
They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.
The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.
The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).
They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.
The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).
The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).
For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)
Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.
That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
Next steps and new questions
Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.
The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.
“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.
Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.
Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”
The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.
Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.
A version of this article first appeared on Medscape.com.
People with metabolic dysfunction–associated fatty liver disease (MAFLD) – a newly defined condition – may be more likely to die from COVID-19, researchers say.
A cohort of people hospitalized for COVID-19 in Central Military Hospital, Mexico City, who met the criteria for MAFLD died at a higher rate than a control group without fatty liver disease, said Martín Uriel Vázquez-Medina, MSc, a researcher in the National Polytechnic Institute in Mexico City.
Patients who met only the criteria for the traditional classification, nonalcoholic fatty liver disease (NAFLD), also died of COVID-19 at a higher rate than the control group, but the difference was not statistically significant.
“It is important to screen for MAFLD,” Mr. Vázquez-Medina told this news organization. “It’s a new definition, but it has really helped us to identify which patients are going to get worse by COVID-19.”
The study was published in Hepatology Communications.
More evidence for clinical relevance of MAFLD
The finding lends support to an initiative to use MAFLD instead of NAFLD to identify patients whose liver steatosis poses a threat to their health, Mr. Vázquez-Medina said.
NAFLD affects as much as a quarter of the world’s population. No drugs have been approved to treat it. Some researchers have reasoned that the imprecision of the definition of NAFLD could be one reason for the lack of progress in treatment.
“NAFLD is something that doesn’t have positive criteria to be diagnosed,” said Mr. Vázquez-Medina. “You only say NAFLD when you don’t find hepatitis or another disease.”
In an article published in Gastroenterology, an international consensus panel proposed MAFLD as an alternative, arguing that a focus on metabolic dysfunction could more accurately reflect the pathogenesis of the disease and help stratify patients.
Previous research has suggested that patients with MAFLD have a higher risk of atherosclerotic cardiovascular disease and that the prevalence of colorectal adenomas is a higher in these patients, compared with patients with NAFLD.
The high prevalence of MAFLD in Mexico – about 30% – could help explain the country’s high rate of mortality from COVID-19, Mr. Vázquez-Medina said. Almost 6% of people diagnosed with COVID in Mexico have died from it, according to the Johns Hopkins University and Medical Center Coronavirus Resource Center.
Sorting COVID outcomes by liver steatosis
To understand the interaction of MAFLD, NAFLD, liver fibrosis, and COVID-19, Mr. Vázquez-Medina and his colleagues analyzed the records of all patients admitted to the Central Military Hospital with COVID-19 from April 4, 2020, to June 24, 2020.
They excluded patients for whom complete data were lacking or for whom a liver function test was not conducted in the first 24 hours of hospitalization. Also excluded were patients with significant consumption of alcohol (> 30 g/day for men and > 20 g/day for women) and those with a history of autoimmune liver disease, liver cancer, decompensated cirrhosis, platelet disorders, or myopathies.
The remaining patients were divided into three groups – 220 who met the criteria for MAFLD, 79 who met the criteria for NAFLD but not MAFLD, and 60 other patients as a control group.
The researchers defined MAFLD as the presence of liver steatosis detected with a noninvasive method and one of the following: overweight (body mass index, 25-29.9 kg/m2), type 2 diabetes, or the presence of two metabolic abnormalities (blood pressure > 140/90 mm Hg, plasma triglycerides > 150 mg/dL, plasma high-density lipoprotein cholesterol < 40 mg/dL in men and < 50 mg/dL in women, and prediabetes).
They defined NAFLD as the presence of liver steatosis without the other criteria for MAFLD.
The patients with MAFLD were the most likely to be intubated and were the most likely to die (intubation, 44.09%; mortality, 55%), followed by those with NAFLD (intubation, 40.51%; mortality, 51.9%) and those in the control group (intubation, 20%; mortality, 38.33%).
The difference in mortality between the MAFLD group and the control group was statistically significant (P = .02). The mortality difference between the NAFLD and the control group fell just short of statistical significance (P = .07).
For intubation, the difference between the MAFLD and the control group was highly statistically significant (P = .001), and the difference between the NAFLD and the control group was also statistically significant (P = .01)
Patients with advanced fibrosis and either MAFLD or NAFLD were also more likely to die than patients in the control group with advanced fibrosis.
That’s why screening for MAFLD is important, Mr. Vázquez-Medina said.
Next steps and new questions
Future research should examine whether patients with MAFLD have elevated levels of biomarkers for inflammation, such as interleukin 6, Mr. Vázquez-Medina said. A “chronic low proinflammatory state” may be the key to understanding the vulnerability of patients to MAFLD to COVID-19, he speculated.
The metabolic traits associated with MAFLD could explain the higher mortality and intubation rates with COVID, said Rohit Loomba, MD, MHSc, a professor of medicine in the division of gastroenterology at the University of California, San Diego, who was not involved in the study.
“Hypertension, diabetes, and obesity increase the risk of complications from COVID in all patients, whether they have been diagnosed with NAFLD or not,” he told this news organization in an email.
Mr. Vasquez-Medina pointed out that the patients with MAFLD had a higher risk of mortality even after adjusting for age, sex, type 2 diabetes, hypertension, overweight, and obesity (BMI ≥ 30 kg/m2). MAFLD also was more strongly associated with a poor outcome than either hypertension alone or obesity alone. Only age emerged as a significant independent covariate in the study.
Dr. Loomba also questioned whether the regression model used in this study for liver steatosis was “fully reflective of NAFLD.”
The researchers identified liver steatosis with a diagnostic formula that used noninvasive clinical BMI and laboratory tests (alanine aminotransferase), citing a study that found the regression formula was better at diagnosing NAFLD than FibroScan.
Mr. Vázquez-Medina reported no relevant financial relationships. Dr. Loomba serves as a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse Bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. He is co-founder of LipoNexus.
A version of this article first appeared on Medscape.com.
FROM HEPATOLOGY COMMUNICATIONS
Clinical chest images power up survival prediction in lung cancer
In patients with stage I lung cancer, adding noncancerous features from CT chest imaging predicts overall survival better than clinical characteristics alone, according to a paper published online in the American Journal of Roentgenology.
Modeling that incorporates noncancerous imaging features captured on chest computed tomography (CT) along with clinical features, when calculated before stereotactic body radiation therapy (SBRT) is administered, improves survival prediction, compared with modeling that relies only on clinical features, the authors report.
“The focus of the study was to look at the environment in which the cancer lives,” said senior author Florian J. Fintelmann, MD, radiologist at Massachusetts General Hospital and associate professor of radiology at Harvard Medical School, both in Boston. “This is looking at parameters like the aortic diameter, body composition – that is, the quantification and characterization of adipose tissue and muscle – coronary artery calcifications, and emphysema quantification.”
CT images are used by radiation oncologists to determine where the radiation should be delivered. “There is more information from these images that we can utilize,” he said.
Survival estimates in patients with state I lung cancer now rely on biological age, ECOG (Eastern Cooperative Oncology Group) score, and the presence of comorbidities, Dr. Fintelmann said.
This retrospective investigation involved 282 patients with a median age of 75 years. There were 168 women and 114 men. All patients had stage I lung cancer and were treated with SBRT between January 2009 and June 2017.
Investigators analyzed pre-treatment chest images with CT. They assessed coronary artery calcium (CAC) score (see above image), pulmonary artery (PA)-to-aorta ratio, emphysema, and several measures of body composition (skeletal muscle and adipose tissue). They developed a statistical model to link clinical and imaging features with overall survival.
An elevated CAC score (11-399: HR, 1.83 [95% confidence interval, 1.15-2.91]; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63]), increased PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], per 0.1-unit increase) and decreased thoracic skeletal muscle (HR, 0.88 [95% CI, 0.79-0.98], per 10 cm2/m2 increase) were independently associated with shorter overall survival, investigators observed.
In addition, 5-year overall survival was superior for the model that included clinical and imaging features and inferior for the model restricted to only clinical features. Of all features, the one that emerged the most predictive of overall survival was PA-to-aorta ratio.
In this single-center study of stage I lung cancer patients who were undergoing SBRT, increased CAC score, increased PA-to-aorta ratio, and decreased thoracic skeletal muscle index were independently predictive of poorer overall survival.
“Our modeling shows that these imaging features add so much more [to predicting overall survival],” Dr. Fintelmann said. “The strength of this study is that we show the utility [of the model] and how it exceeds the clinical risk prediction that is currently standard of care. We think this will benefit patients in terms of being able to counsel them and better advise them on their medical decisions.”
This proof-of-concept investigation requires external validation, Dr. Fintelmann stressed. “External data for validation is the next step,” he said, noting he and co-investigators welcome data input from other investigators.
Elsie Nguyen, MD, FRCPC, FNASCI, associate professor of radiology, University of Toronto, responded by email that the study shows that imaging features supplement clinical data in predicting overall survival.
“This study demonstrates the value of extracting non–cancer related computed tomography imaging features to build a model that can better predict overall survival as compared to clinical parameters alone (such as age, performance status and co-morbidities) for stage I lung cancer patients treated with SBRT,” Dr. Nguyen wrote.
“Coronary artery calcium score, pulmonary artery-to-aorta ratio, and sarcopenia independently predicted overall survival,” she wrote. “These results are not surprising, as the prognostic value of each of these imaging features has already been established in the literature.”
Dr. Nguyen pointed out the power in the sum of these imaging features to predict overall survival.
“However, the results of this study demonstrate promising results supportive of the notion that combining clinical and imaging data points can help build a more accurate prediction model for overall survival,” she wrote. “This is analogous to the Brock University (in St. Catharines, Ontario) calculator for solitary pulmonary nodules that calculates malignancy risk based on both clinical and imaging data points. However, external validation of these study results at other centers is first required.”
Dr. Fintelmann and Dr. Nguyen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In patients with stage I lung cancer, adding noncancerous features from CT chest imaging predicts overall survival better than clinical characteristics alone, according to a paper published online in the American Journal of Roentgenology.
Modeling that incorporates noncancerous imaging features captured on chest computed tomography (CT) along with clinical features, when calculated before stereotactic body radiation therapy (SBRT) is administered, improves survival prediction, compared with modeling that relies only on clinical features, the authors report.
“The focus of the study was to look at the environment in which the cancer lives,” said senior author Florian J. Fintelmann, MD, radiologist at Massachusetts General Hospital and associate professor of radiology at Harvard Medical School, both in Boston. “This is looking at parameters like the aortic diameter, body composition – that is, the quantification and characterization of adipose tissue and muscle – coronary artery calcifications, and emphysema quantification.”
CT images are used by radiation oncologists to determine where the radiation should be delivered. “There is more information from these images that we can utilize,” he said.
Survival estimates in patients with state I lung cancer now rely on biological age, ECOG (Eastern Cooperative Oncology Group) score, and the presence of comorbidities, Dr. Fintelmann said.
This retrospective investigation involved 282 patients with a median age of 75 years. There were 168 women and 114 men. All patients had stage I lung cancer and were treated with SBRT between January 2009 and June 2017.
Investigators analyzed pre-treatment chest images with CT. They assessed coronary artery calcium (CAC) score (see above image), pulmonary artery (PA)-to-aorta ratio, emphysema, and several measures of body composition (skeletal muscle and adipose tissue). They developed a statistical model to link clinical and imaging features with overall survival.
An elevated CAC score (11-399: HR, 1.83 [95% confidence interval, 1.15-2.91]; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63]), increased PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], per 0.1-unit increase) and decreased thoracic skeletal muscle (HR, 0.88 [95% CI, 0.79-0.98], per 10 cm2/m2 increase) were independently associated with shorter overall survival, investigators observed.
In addition, 5-year overall survival was superior for the model that included clinical and imaging features and inferior for the model restricted to only clinical features. Of all features, the one that emerged the most predictive of overall survival was PA-to-aorta ratio.
In this single-center study of stage I lung cancer patients who were undergoing SBRT, increased CAC score, increased PA-to-aorta ratio, and decreased thoracic skeletal muscle index were independently predictive of poorer overall survival.
“Our modeling shows that these imaging features add so much more [to predicting overall survival],” Dr. Fintelmann said. “The strength of this study is that we show the utility [of the model] and how it exceeds the clinical risk prediction that is currently standard of care. We think this will benefit patients in terms of being able to counsel them and better advise them on their medical decisions.”
This proof-of-concept investigation requires external validation, Dr. Fintelmann stressed. “External data for validation is the next step,” he said, noting he and co-investigators welcome data input from other investigators.
Elsie Nguyen, MD, FRCPC, FNASCI, associate professor of radiology, University of Toronto, responded by email that the study shows that imaging features supplement clinical data in predicting overall survival.
“This study demonstrates the value of extracting non–cancer related computed tomography imaging features to build a model that can better predict overall survival as compared to clinical parameters alone (such as age, performance status and co-morbidities) for stage I lung cancer patients treated with SBRT,” Dr. Nguyen wrote.
“Coronary artery calcium score, pulmonary artery-to-aorta ratio, and sarcopenia independently predicted overall survival,” she wrote. “These results are not surprising, as the prognostic value of each of these imaging features has already been established in the literature.”
Dr. Nguyen pointed out the power in the sum of these imaging features to predict overall survival.
“However, the results of this study demonstrate promising results supportive of the notion that combining clinical and imaging data points can help build a more accurate prediction model for overall survival,” she wrote. “This is analogous to the Brock University (in St. Catharines, Ontario) calculator for solitary pulmonary nodules that calculates malignancy risk based on both clinical and imaging data points. However, external validation of these study results at other centers is first required.”
Dr. Fintelmann and Dr. Nguyen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In patients with stage I lung cancer, adding noncancerous features from CT chest imaging predicts overall survival better than clinical characteristics alone, according to a paper published online in the American Journal of Roentgenology.
Modeling that incorporates noncancerous imaging features captured on chest computed tomography (CT) along with clinical features, when calculated before stereotactic body radiation therapy (SBRT) is administered, improves survival prediction, compared with modeling that relies only on clinical features, the authors report.
“The focus of the study was to look at the environment in which the cancer lives,” said senior author Florian J. Fintelmann, MD, radiologist at Massachusetts General Hospital and associate professor of radiology at Harvard Medical School, both in Boston. “This is looking at parameters like the aortic diameter, body composition – that is, the quantification and characterization of adipose tissue and muscle – coronary artery calcifications, and emphysema quantification.”
CT images are used by radiation oncologists to determine where the radiation should be delivered. “There is more information from these images that we can utilize,” he said.
Survival estimates in patients with state I lung cancer now rely on biological age, ECOG (Eastern Cooperative Oncology Group) score, and the presence of comorbidities, Dr. Fintelmann said.
This retrospective investigation involved 282 patients with a median age of 75 years. There were 168 women and 114 men. All patients had stage I lung cancer and were treated with SBRT between January 2009 and June 2017.
Investigators analyzed pre-treatment chest images with CT. They assessed coronary artery calcium (CAC) score (see above image), pulmonary artery (PA)-to-aorta ratio, emphysema, and several measures of body composition (skeletal muscle and adipose tissue). They developed a statistical model to link clinical and imaging features with overall survival.
An elevated CAC score (11-399: HR, 1.83 [95% confidence interval, 1.15-2.91]; ≥ 400: HR, 1.63 [95% CI, 1.01-2.63]), increased PA-to-aorta ratio (HR, 1.33 [95% CI, 1.16-1.52], per 0.1-unit increase) and decreased thoracic skeletal muscle (HR, 0.88 [95% CI, 0.79-0.98], per 10 cm2/m2 increase) were independently associated with shorter overall survival, investigators observed.
In addition, 5-year overall survival was superior for the model that included clinical and imaging features and inferior for the model restricted to only clinical features. Of all features, the one that emerged the most predictive of overall survival was PA-to-aorta ratio.
In this single-center study of stage I lung cancer patients who were undergoing SBRT, increased CAC score, increased PA-to-aorta ratio, and decreased thoracic skeletal muscle index were independently predictive of poorer overall survival.
“Our modeling shows that these imaging features add so much more [to predicting overall survival],” Dr. Fintelmann said. “The strength of this study is that we show the utility [of the model] and how it exceeds the clinical risk prediction that is currently standard of care. We think this will benefit patients in terms of being able to counsel them and better advise them on their medical decisions.”
This proof-of-concept investigation requires external validation, Dr. Fintelmann stressed. “External data for validation is the next step,” he said, noting he and co-investigators welcome data input from other investigators.
Elsie Nguyen, MD, FRCPC, FNASCI, associate professor of radiology, University of Toronto, responded by email that the study shows that imaging features supplement clinical data in predicting overall survival.
“This study demonstrates the value of extracting non–cancer related computed tomography imaging features to build a model that can better predict overall survival as compared to clinical parameters alone (such as age, performance status and co-morbidities) for stage I lung cancer patients treated with SBRT,” Dr. Nguyen wrote.
“Coronary artery calcium score, pulmonary artery-to-aorta ratio, and sarcopenia independently predicted overall survival,” she wrote. “These results are not surprising, as the prognostic value of each of these imaging features has already been established in the literature.”
Dr. Nguyen pointed out the power in the sum of these imaging features to predict overall survival.
“However, the results of this study demonstrate promising results supportive of the notion that combining clinical and imaging data points can help build a more accurate prediction model for overall survival,” she wrote. “This is analogous to the Brock University (in St. Catharines, Ontario) calculator for solitary pulmonary nodules that calculates malignancy risk based on both clinical and imaging data points. However, external validation of these study results at other centers is first required.”
Dr. Fintelmann and Dr. Nguyen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Don’t let FOMI lead to antibiotic overuse
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?
Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.
All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?
Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.
Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”
“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
Rampant misuse
Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.
“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.
“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”
The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
How to be a better steward
The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.
All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.
Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”
Clinicians should also:
- Observe antibiotic best practices
- Optimize antibiotic selection and dosing
- Practice effective diagnostic stewardship
- Use the shortest duration of therapy necessary
- Avoid antibiotics for inappropriate indications
- Educate patients on when antibiotics are needed
- Follow and become good antibiotic stewardship mentors
“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”
Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2022
Depression biomarkers: Which ones matter most?
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Multiple biomarkers of depression involved in several brain circuits are altered in patients with unipolar depression.
because they suggest neuroimmunological alterations, disturbances in the blood-brain-barrier, hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, and impaired neuroplasticity as factors in depression pathophysiology.
However, said study investigator Michael E. Benros, MD, PhD, professor and head of research at Mental Health Centre Copenhagen and University of Copenhagen, this is on a group level. “So in order to be relevant in a clinical context, the results need to be validated by further high-quality studies identifying subgroups with different biological underpinnings,” he told this news organization.
Identification of potential subgroups of depression with different biomarkers might help explain the diverse symptomatology and variability in treatment response observed in patients with depression, he noted.
The study was published online in JAMA Psychiatry.
Multiple pathways to depression
The systematic review and meta-analysis included 97 studies investigating 165 CSF biomarkers.
Of the 42 biomarkers investigated in at least two studies, patients with unipolar depression had higher CSF levels of interleukin 6, a marker of chronic inflammation; total protein, which signals blood-brain barrier dysfunction and increased permeability; and cortisol, which is linked to psychological stress, compared with healthy controls.
Depression was also associated with:
- Lower CSF levels of homovanillic acid, the major terminal metabolite of dopamine.
- Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS thought to play a vital role in the control of stress and depression.
- Somatostatin, a neuropeptide often coexpressed with GABA.
- Brain-derived neurotrophic factor (BDNF), a protein involved in neurogenesis, synaptic plasticity, and neurotransmission.
- Amyloid-β 40, implicated in Alzheimer’s disease.
- Transthyretin, involved in transport of thyroxine across the blood-brain barrier.
Collectively, the findings point toward a “dysregulated dopaminergic system, a compromised inhibitory system, HPA axis hyperactivity, increased neuroinflammation and blood-brain barrier permeability, and impaired neuroplasticity as important factors in depression pathophysiology,” the investigators wrote.
“It is notable that we did not find significant difference in the metabolite levels of serotonin and noradrenalin, which are the most targeted neurotransmitters in modern antidepressant treatment,” said Dr. Benros.
However, this could be explained by substantial heterogeneity between studies and the fact that quantification of total CSF biomarker concentrations does not reflect local alteration within the brain, he explained.
Many of the studies had small cohorts and most quantified only a few biomarkers, making it hard to examine potential interactions between biomarkers or identify specific phenotypes of depression.
“Novel high-quality studies including larger cohorts with an integrative approach and extensive numbers of biomarkers are needed to validate these potential biomarkers of depression and set the stage for the development of more effective and precise treatments,” the researchers noted.
Which ones hold water?
Reached for comment, Dean MacKinnon, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, noted that this analysis “extracts the vast amount of knowledge” gained from different studies on biomarkers in the CSF for depression.
“They were able to identify 97 papers that have enough information in them that they could sort of lump them together and see which ones still hold water. It’s always useful to be able to look at patterns in the research and see if you can find some consistent trends,” he told this news organization.
Dr. MacKinnon, who was not part of the research team, also noted that “nonreplicability” is a problem in psychiatry and psychology research, “so being able to show that at least some studies were sufficiently well done, to get a good result, and that they could be replicated in at least one other good study is useful information.”
When it comes to depression, Dr. MacKinnon said, “We just don’t know enough to really pin down a physiologic pathway to explain it. The fact that some people seem to have high cortisol and some people seem to have high permeability of blood-brain barrier, and others have abnormalities in dopamine, is interesting and suggests that depression is likely not a unitary disease with a single cause.”
He cautioned, however, that the findings don’t have immediate clinical implications for individual patients with depression.
“Theoretically, down the road, if you extrapolate from what they found, and if it’s truly the case that this research maps to something that could suggest a different clinical approach, you might be able to determine whether one patient might respond better to an SSRI or an SNRI or something like that,” Dr. MacKinnon said.
Dr. Benros reported grants from Lundbeck Foundation during the conduct of the study. Dr. MacKinnon has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Burnout ‘highly prevalent’ in psychiatrists across the globe
Burnout in psychiatrists is “highly prevalent” across the globe, new research shows.
In a review and meta-analysis of 36 studies and more than 5,000 psychiatrists in European countries, as well as the United States, Australia, New Zealand, India, Turkey, and Thailand,
“Our review showed that regardless of the identification method of burnout, its prevalence among psychiatrists is high and ranges from 25% to 50%,” lead author Kirill Bykov, MD, a PhD candidate at the Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation, told this news organization.
There was a “high heterogeneity of studies in terms of statistics, screening methods, burnout definitions, and cutoff points in the included studies, which necessitates the unification of future research methodology, but not to the detriment of the development of the theoretical background,” Dr. Bykov said.
The findings were published online in the Journal of Affective Disorders.
‘Unresolved problem’
Although burnout is a serious and prevalent problem among health care workers, little research has focused on burnout in mental health workers compared with other professionals, the investigators noted.
A previous systematic review and meta-analysis that focused specifically on burnout in psychiatrists was limited by methodologic concerns, including that the only burnout screening instrument used in the included studies was the full-length (22-item) MBI.
The current researchers surmised that “the integration of different empirical studies of psychiatrists’ burnout prevalence [remained] an unresolved problem.”
Dr. Bykov noted the current review was “investigator-initiated” and was a part of his PhD dissertation.
“Studying the works devoted to the burnout of psychiatrists, I drew attention to the varying prevalence rates of this phenomenon among them. This prompted me to conduct a systematic review of the literature and summarize the available data,” he said.
Unlike the previous review, the current one “does not contain restrictions regarding the place of research, publication language, covered burnout concepts, definitions, and screening instruments. Thus, its results will be helpful for practitioners and scientists around the world,” Dr. Bykov added.
Among the inclusion criteria was that a study should be empirical and quantitative, contain at least 20 practicing psychiatrists as participants, use a valid and reliable burnout screening instrument, have at least one burnout metric extractable specifically with regard to psychiatrists, and have a national survey or a response rate among psychiatrists of 20% or greater.
Qualitative or review articles or studies consisting of psychiatric trainees (such as medical students or residents) or nonpracticing psychiatrists were excluded.
Pooled prevalence
The researchers included 36 studies that comprised 5,481 participants (51.3% were women; mean age, 46.7 years). All studies had from 20 to 1,157 participants. They were employed in an array of settings in 19 countries.
In 22 studies, survey years ranged from 1996 to 2018; 14 studies did not report the year of data collection.
Most studies (75%) used some version of the MBI, and 19 studies used the full-length 22-item MBI Human Service Survey (MBI-HSS) . The survey rates emotional exhaustion (EE), depersonalization (DP), and low personal achievement (PA) on a 7-point Likert scale from 0 (“never”) to 6 (“almost every day”).
Other instruments included the CBI, the 16-item Oldenburg Burnout Inventory, the 21-item Tedium Measure, the 30-item Professional Quality of Life measure, the Rohland et al. Single-Item Measure of Self-Perceived Burnout, and the 21-item Brief Burnout Questionnaire.
Only three studies were free of methodologic limitations. The remaining 33 studies had some problems, such as not reporting the response rate or comparability between responders and nonresponders.
Results showed that the overall prevalence of burnout, as measured by the MBI and the CBI, was 25.9% (range, 11.1%-40.75%) and 50.3% (range, 30.9%-69.8%), respectively.
The pooled prevalence for burnout components is shown in the table.
European psychiatrists had lower EE scores (20.82; 95% confidence interval, 7.24-4.41) compared with their non-European counterparts (24.99; 95% CI, 23.05-26.94; P = .045).
‘Carry the hope’
In a comment, Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness (NAMI), said she was surprised the burnout numbers weren’t higher.
Many colleagues she interacts with “have been experiencing pretty significant burnout that has only been exacerbated by the pandemic and ever-growing demand for mental health providers, and there aren’t enough to meet that demand,” said Dr. Crawford, a psychiatrist at Boston Medical Center’s Outpatient Child and Adolescent Psychiatry Clinic and at Codman Square Health Center. She was not involved with the current research.
Dr. Crawford noted that much of the data was from Europeans. Speaking to the experience of U.S.-based psychiatrists, she said there is a “greater appreciation for what we do as mental health providers, due to the growing conversations around mental health and normalizing mental health conditions.”
On the other hand, there is “a lack of parity in reimbursement rates. Although the general public values mental health, the medical system doesn’t value mental health providers in the same way as physicians in other specialties,” Dr. Crawford said. Feeling devalued can contribute to burnout, she added.
One way to counter burnout is to remember “that our role is to carry the hope. We can be hopeful for the patient that the treatment will work or the medications can provide some relief,” Dr. Crawford noted.
Psychiatrists “may need to hold on tightly to that hope because we may not receive that instant gratification from the patient or receive praise or see the change from the patient during that time, which can be challenging,” she said.
“But it’s important for us to keep in mind that, even in that moment when the patient can’t see it, we can work alongside the patient to create the vision of hope and what it will look like in the future,” said Dr. Crawford.
In the 2022 Medscape Psychiatrist Lifestyle, Happiness & Burnout Report, an annual online survey of Medscape member physicians, 47% of respondents reported burnout – which was up from 42% the previous year.
The investigators received no funding for this work. They and Dr. Crawford report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Burnout in psychiatrists is “highly prevalent” across the globe, new research shows.
In a review and meta-analysis of 36 studies and more than 5,000 psychiatrists in European countries, as well as the United States, Australia, New Zealand, India, Turkey, and Thailand,
“Our review showed that regardless of the identification method of burnout, its prevalence among psychiatrists is high and ranges from 25% to 50%,” lead author Kirill Bykov, MD, a PhD candidate at the Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation, told this news organization.
There was a “high heterogeneity of studies in terms of statistics, screening methods, burnout definitions, and cutoff points in the included studies, which necessitates the unification of future research methodology, but not to the detriment of the development of the theoretical background,” Dr. Bykov said.
The findings were published online in the Journal of Affective Disorders.
‘Unresolved problem’
Although burnout is a serious and prevalent problem among health care workers, little research has focused on burnout in mental health workers compared with other professionals, the investigators noted.
A previous systematic review and meta-analysis that focused specifically on burnout in psychiatrists was limited by methodologic concerns, including that the only burnout screening instrument used in the included studies was the full-length (22-item) MBI.
The current researchers surmised that “the integration of different empirical studies of psychiatrists’ burnout prevalence [remained] an unresolved problem.”
Dr. Bykov noted the current review was “investigator-initiated” and was a part of his PhD dissertation.
“Studying the works devoted to the burnout of psychiatrists, I drew attention to the varying prevalence rates of this phenomenon among them. This prompted me to conduct a systematic review of the literature and summarize the available data,” he said.
Unlike the previous review, the current one “does not contain restrictions regarding the place of research, publication language, covered burnout concepts, definitions, and screening instruments. Thus, its results will be helpful for practitioners and scientists around the world,” Dr. Bykov added.
Among the inclusion criteria was that a study should be empirical and quantitative, contain at least 20 practicing psychiatrists as participants, use a valid and reliable burnout screening instrument, have at least one burnout metric extractable specifically with regard to psychiatrists, and have a national survey or a response rate among psychiatrists of 20% or greater.
Qualitative or review articles or studies consisting of psychiatric trainees (such as medical students or residents) or nonpracticing psychiatrists were excluded.
Pooled prevalence
The researchers included 36 studies that comprised 5,481 participants (51.3% were women; mean age, 46.7 years). All studies had from 20 to 1,157 participants. They were employed in an array of settings in 19 countries.
In 22 studies, survey years ranged from 1996 to 2018; 14 studies did not report the year of data collection.
Most studies (75%) used some version of the MBI, and 19 studies used the full-length 22-item MBI Human Service Survey (MBI-HSS) . The survey rates emotional exhaustion (EE), depersonalization (DP), and low personal achievement (PA) on a 7-point Likert scale from 0 (“never”) to 6 (“almost every day”).
Other instruments included the CBI, the 16-item Oldenburg Burnout Inventory, the 21-item Tedium Measure, the 30-item Professional Quality of Life measure, the Rohland et al. Single-Item Measure of Self-Perceived Burnout, and the 21-item Brief Burnout Questionnaire.
Only three studies were free of methodologic limitations. The remaining 33 studies had some problems, such as not reporting the response rate or comparability between responders and nonresponders.
Results showed that the overall prevalence of burnout, as measured by the MBI and the CBI, was 25.9% (range, 11.1%-40.75%) and 50.3% (range, 30.9%-69.8%), respectively.
The pooled prevalence for burnout components is shown in the table.
European psychiatrists had lower EE scores (20.82; 95% confidence interval, 7.24-4.41) compared with their non-European counterparts (24.99; 95% CI, 23.05-26.94; P = .045).
‘Carry the hope’
In a comment, Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness (NAMI), said she was surprised the burnout numbers weren’t higher.
Many colleagues she interacts with “have been experiencing pretty significant burnout that has only been exacerbated by the pandemic and ever-growing demand for mental health providers, and there aren’t enough to meet that demand,” said Dr. Crawford, a psychiatrist at Boston Medical Center’s Outpatient Child and Adolescent Psychiatry Clinic and at Codman Square Health Center. She was not involved with the current research.
Dr. Crawford noted that much of the data was from Europeans. Speaking to the experience of U.S.-based psychiatrists, she said there is a “greater appreciation for what we do as mental health providers, due to the growing conversations around mental health and normalizing mental health conditions.”
On the other hand, there is “a lack of parity in reimbursement rates. Although the general public values mental health, the medical system doesn’t value mental health providers in the same way as physicians in other specialties,” Dr. Crawford said. Feeling devalued can contribute to burnout, she added.
One way to counter burnout is to remember “that our role is to carry the hope. We can be hopeful for the patient that the treatment will work or the medications can provide some relief,” Dr. Crawford noted.
Psychiatrists “may need to hold on tightly to that hope because we may not receive that instant gratification from the patient or receive praise or see the change from the patient during that time, which can be challenging,” she said.
“But it’s important for us to keep in mind that, even in that moment when the patient can’t see it, we can work alongside the patient to create the vision of hope and what it will look like in the future,” said Dr. Crawford.
In the 2022 Medscape Psychiatrist Lifestyle, Happiness & Burnout Report, an annual online survey of Medscape member physicians, 47% of respondents reported burnout – which was up from 42% the previous year.
The investigators received no funding for this work. They and Dr. Crawford report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Burnout in psychiatrists is “highly prevalent” across the globe, new research shows.
In a review and meta-analysis of 36 studies and more than 5,000 psychiatrists in European countries, as well as the United States, Australia, New Zealand, India, Turkey, and Thailand,
“Our review showed that regardless of the identification method of burnout, its prevalence among psychiatrists is high and ranges from 25% to 50%,” lead author Kirill Bykov, MD, a PhD candidate at the Peoples’ Friendship University of Russia (RUDN University), Moscow, Russian Federation, told this news organization.
There was a “high heterogeneity of studies in terms of statistics, screening methods, burnout definitions, and cutoff points in the included studies, which necessitates the unification of future research methodology, but not to the detriment of the development of the theoretical background,” Dr. Bykov said.
The findings were published online in the Journal of Affective Disorders.
‘Unresolved problem’
Although burnout is a serious and prevalent problem among health care workers, little research has focused on burnout in mental health workers compared with other professionals, the investigators noted.
A previous systematic review and meta-analysis that focused specifically on burnout in psychiatrists was limited by methodologic concerns, including that the only burnout screening instrument used in the included studies was the full-length (22-item) MBI.
The current researchers surmised that “the integration of different empirical studies of psychiatrists’ burnout prevalence [remained] an unresolved problem.”
Dr. Bykov noted the current review was “investigator-initiated” and was a part of his PhD dissertation.
“Studying the works devoted to the burnout of psychiatrists, I drew attention to the varying prevalence rates of this phenomenon among them. This prompted me to conduct a systematic review of the literature and summarize the available data,” he said.
Unlike the previous review, the current one “does not contain restrictions regarding the place of research, publication language, covered burnout concepts, definitions, and screening instruments. Thus, its results will be helpful for practitioners and scientists around the world,” Dr. Bykov added.
Among the inclusion criteria was that a study should be empirical and quantitative, contain at least 20 practicing psychiatrists as participants, use a valid and reliable burnout screening instrument, have at least one burnout metric extractable specifically with regard to psychiatrists, and have a national survey or a response rate among psychiatrists of 20% or greater.
Qualitative or review articles or studies consisting of psychiatric trainees (such as medical students or residents) or nonpracticing psychiatrists were excluded.
Pooled prevalence
The researchers included 36 studies that comprised 5,481 participants (51.3% were women; mean age, 46.7 years). All studies had from 20 to 1,157 participants. They were employed in an array of settings in 19 countries.
In 22 studies, survey years ranged from 1996 to 2018; 14 studies did not report the year of data collection.
Most studies (75%) used some version of the MBI, and 19 studies used the full-length 22-item MBI Human Service Survey (MBI-HSS) . The survey rates emotional exhaustion (EE), depersonalization (DP), and low personal achievement (PA) on a 7-point Likert scale from 0 (“never”) to 6 (“almost every day”).
Other instruments included the CBI, the 16-item Oldenburg Burnout Inventory, the 21-item Tedium Measure, the 30-item Professional Quality of Life measure, the Rohland et al. Single-Item Measure of Self-Perceived Burnout, and the 21-item Brief Burnout Questionnaire.
Only three studies were free of methodologic limitations. The remaining 33 studies had some problems, such as not reporting the response rate or comparability between responders and nonresponders.
Results showed that the overall prevalence of burnout, as measured by the MBI and the CBI, was 25.9% (range, 11.1%-40.75%) and 50.3% (range, 30.9%-69.8%), respectively.
The pooled prevalence for burnout components is shown in the table.
European psychiatrists had lower EE scores (20.82; 95% confidence interval, 7.24-4.41) compared with their non-European counterparts (24.99; 95% CI, 23.05-26.94; P = .045).
‘Carry the hope’
In a comment, Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness (NAMI), said she was surprised the burnout numbers weren’t higher.
Many colleagues she interacts with “have been experiencing pretty significant burnout that has only been exacerbated by the pandemic and ever-growing demand for mental health providers, and there aren’t enough to meet that demand,” said Dr. Crawford, a psychiatrist at Boston Medical Center’s Outpatient Child and Adolescent Psychiatry Clinic and at Codman Square Health Center. She was not involved with the current research.
Dr. Crawford noted that much of the data was from Europeans. Speaking to the experience of U.S.-based psychiatrists, she said there is a “greater appreciation for what we do as mental health providers, due to the growing conversations around mental health and normalizing mental health conditions.”
On the other hand, there is “a lack of parity in reimbursement rates. Although the general public values mental health, the medical system doesn’t value mental health providers in the same way as physicians in other specialties,” Dr. Crawford said. Feeling devalued can contribute to burnout, she added.
One way to counter burnout is to remember “that our role is to carry the hope. We can be hopeful for the patient that the treatment will work or the medications can provide some relief,” Dr. Crawford noted.
Psychiatrists “may need to hold on tightly to that hope because we may not receive that instant gratification from the patient or receive praise or see the change from the patient during that time, which can be challenging,” she said.
“But it’s important for us to keep in mind that, even in that moment when the patient can’t see it, we can work alongside the patient to create the vision of hope and what it will look like in the future,” said Dr. Crawford.
In the 2022 Medscape Psychiatrist Lifestyle, Happiness & Burnout Report, an annual online survey of Medscape member physicians, 47% of respondents reported burnout – which was up from 42% the previous year.
The investigators received no funding for this work. They and Dr. Crawford report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Cellular gene profiling may predict IBD treatment response
Transcriptomic profiling of phagocytes in the lamina propria of patients with inflammatory bowel disease (IBD) may guide future treatment selection, according to investigators.
Mucosal gut biopsies revealed that phagocytic gene expression correlated with inflammatory states, types of IBD, and responses to therapy, lead author Gillian E. Jacobsen a MD/PhD candidate at the University of Miami and colleagues reported.
In an article in Gastro Hep Advances, the investigators wrote that “lamina propria phagocytes along with epithelial cells represent a first line of defense and play a balancing act between tolerance toward commensal microbes and generation of immune responses toward pathogenic microorganisms. ... Inappropriate responses by lamina propria phagocytes have been linked to IBD.”
To better understand these responses, the researchers collected 111 gut mucosal biopsies from 54 patients with IBD, among whom 59% were taking biologics, 72% had inflammation in at least one biopsy site, and 41% had previously used at least one other biologic. Samples were analyzed to determine cell phenotypes, gene expression, and cytokine responses to in vitro Janus kinase (JAK) inhibitor exposure.
Ms. Jacobsen and colleagues noted that most reports that address the function of phagocytes focus on circulating dendritic cells, monocytes, or monocyte-derived macrophages, rather than on resident phagocyte populations located in the lamina propria. However, these circulating cells “do not reflect intestinal inflammation, or whole tissue biopsies.”
Phagocytes based on CD11b expression and phenotyped CD11b+-enriched cells using flow cytometry were identified. In samples with active inflammation, cells were most often granulocytes (45.5%), followed by macrophages (22.6%) and monocytes (9.4%). Uninflamed samples had a slightly lower proportion of granulocytes (33.6%), about the same proportion of macrophages (22.7%), and a higher rate of B cells (15.6% vs. 9.0%).
Ms. Jacobsen and colleagues highlighted the absolute uptick in granulocytes, including neutrophils.
“Neutrophilic infiltration is a major indicator of IBD activity and may be critically linked to ongoing inflammation,” they wrote. “These data demonstrate that CD11b+ enrichment reflects the inflammatory state of the biopsies.”
The investigators also showed that transcriptional profiles of lamina propria CD11b+ cells differed “greatly” between colon and ileum, which suggested that “the location or cellular environment plays a marked role in determining the gene expression of phagocytes.”
CD11b+ cell gene expression profiles also correlated with ulcerative colitis versus Crohn’s disease, although the researchers noted that these patterns were less pronounced than correlations with inflammatory states
“There are pathways common to inflammation regardless of the IBD type that could be used as markers of inflammation or targets for therapy.”
Comparing colon samples from patients who responded to anti–tumor necrosis factor therapy with those who were refractory to anti-TNF therapy revealed significant associations between response type and 52 differentially expressed genes.
“These genes were mostly immunoglobulin genes up-regulated in the anti–TNF-treated inflamed colon, suggesting that CD11b+ B cells may play a role in medication refractoriness.”
Evaluating inflamed colon and anti-TNF refractory ileum revealed differential expression of OSM, a known marker of TNF-resistant disease, as well as TREM1, a proinflammatory marker. In contrast, NTS genes showed high expression in uninflamed samples on anti-TNF therapy. The researchers noted that these findings “may be used to build precision medicine approaches in IBD.”
Further experiments showed that in vitro exposure of anti-TNF refractory samples to JAK inhibitors resulted in significantly reduced secretion of interleukin-8 and TNF-alpha.
“Our study provides functional data that JAK inhibition with tofacitinib (JAK1/JAK3) or ruxolitinib (JAK1/JAK2) inhibits lipopolysaccharide-induced cytokine production even in TNF-refractory samples,” the researchers wrote. “These data inform the response of patients to JAK inhibitors, including those refractory to other treatments.”
The study was supported by Pfizer, the National Institute of Diabetes and Digestive and Kidney Diseases, the Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and Martin Kalser Chair in Gastroenterology at the University of Miami. The investigators disclosed additional relationships with Takeda, Abbvie, Eli Lilly, and others.
Inflammatory bowel diseases are complex and heterogenous disorders driven by inappropriate immune responses to luminal substances, including diet and microbes, resulting in chronic inflammation of the gastrointestinal tract. Therapies for IBD largely center around suppressing immune responses; however, given the complexity and heterogeneity of these diseases, consensus on which aspect of the immune response to suppress and which cell type to target in a given patient is unclear.
Sreeram Udayan, PhD, and Rodney D. Newberry, MD, are with the division of gastroenterology in the department of medicine at Washington University, St. Louis.
Inflammatory bowel diseases are complex and heterogenous disorders driven by inappropriate immune responses to luminal substances, including diet and microbes, resulting in chronic inflammation of the gastrointestinal tract. Therapies for IBD largely center around suppressing immune responses; however, given the complexity and heterogeneity of these diseases, consensus on which aspect of the immune response to suppress and which cell type to target in a given patient is unclear.
Sreeram Udayan, PhD, and Rodney D. Newberry, MD, are with the division of gastroenterology in the department of medicine at Washington University, St. Louis.
Inflammatory bowel diseases are complex and heterogenous disorders driven by inappropriate immune responses to luminal substances, including diet and microbes, resulting in chronic inflammation of the gastrointestinal tract. Therapies for IBD largely center around suppressing immune responses; however, given the complexity and heterogeneity of these diseases, consensus on which aspect of the immune response to suppress and which cell type to target in a given patient is unclear.
Sreeram Udayan, PhD, and Rodney D. Newberry, MD, are with the division of gastroenterology in the department of medicine at Washington University, St. Louis.
Transcriptomic profiling of phagocytes in the lamina propria of patients with inflammatory bowel disease (IBD) may guide future treatment selection, according to investigators.
Mucosal gut biopsies revealed that phagocytic gene expression correlated with inflammatory states, types of IBD, and responses to therapy, lead author Gillian E. Jacobsen a MD/PhD candidate at the University of Miami and colleagues reported.
In an article in Gastro Hep Advances, the investigators wrote that “lamina propria phagocytes along with epithelial cells represent a first line of defense and play a balancing act between tolerance toward commensal microbes and generation of immune responses toward pathogenic microorganisms. ... Inappropriate responses by lamina propria phagocytes have been linked to IBD.”
To better understand these responses, the researchers collected 111 gut mucosal biopsies from 54 patients with IBD, among whom 59% were taking biologics, 72% had inflammation in at least one biopsy site, and 41% had previously used at least one other biologic. Samples were analyzed to determine cell phenotypes, gene expression, and cytokine responses to in vitro Janus kinase (JAK) inhibitor exposure.
Ms. Jacobsen and colleagues noted that most reports that address the function of phagocytes focus on circulating dendritic cells, monocytes, or monocyte-derived macrophages, rather than on resident phagocyte populations located in the lamina propria. However, these circulating cells “do not reflect intestinal inflammation, or whole tissue biopsies.”
Phagocytes based on CD11b expression and phenotyped CD11b+-enriched cells using flow cytometry were identified. In samples with active inflammation, cells were most often granulocytes (45.5%), followed by macrophages (22.6%) and monocytes (9.4%). Uninflamed samples had a slightly lower proportion of granulocytes (33.6%), about the same proportion of macrophages (22.7%), and a higher rate of B cells (15.6% vs. 9.0%).
Ms. Jacobsen and colleagues highlighted the absolute uptick in granulocytes, including neutrophils.
“Neutrophilic infiltration is a major indicator of IBD activity and may be critically linked to ongoing inflammation,” they wrote. “These data demonstrate that CD11b+ enrichment reflects the inflammatory state of the biopsies.”
The investigators also showed that transcriptional profiles of lamina propria CD11b+ cells differed “greatly” between colon and ileum, which suggested that “the location or cellular environment plays a marked role in determining the gene expression of phagocytes.”
CD11b+ cell gene expression profiles also correlated with ulcerative colitis versus Crohn’s disease, although the researchers noted that these patterns were less pronounced than correlations with inflammatory states
“There are pathways common to inflammation regardless of the IBD type that could be used as markers of inflammation or targets for therapy.”
Comparing colon samples from patients who responded to anti–tumor necrosis factor therapy with those who were refractory to anti-TNF therapy revealed significant associations between response type and 52 differentially expressed genes.
“These genes were mostly immunoglobulin genes up-regulated in the anti–TNF-treated inflamed colon, suggesting that CD11b+ B cells may play a role in medication refractoriness.”
Evaluating inflamed colon and anti-TNF refractory ileum revealed differential expression of OSM, a known marker of TNF-resistant disease, as well as TREM1, a proinflammatory marker. In contrast, NTS genes showed high expression in uninflamed samples on anti-TNF therapy. The researchers noted that these findings “may be used to build precision medicine approaches in IBD.”
Further experiments showed that in vitro exposure of anti-TNF refractory samples to JAK inhibitors resulted in significantly reduced secretion of interleukin-8 and TNF-alpha.
“Our study provides functional data that JAK inhibition with tofacitinib (JAK1/JAK3) or ruxolitinib (JAK1/JAK2) inhibits lipopolysaccharide-induced cytokine production even in TNF-refractory samples,” the researchers wrote. “These data inform the response of patients to JAK inhibitors, including those refractory to other treatments.”
The study was supported by Pfizer, the National Institute of Diabetes and Digestive and Kidney Diseases, the Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and Martin Kalser Chair in Gastroenterology at the University of Miami. The investigators disclosed additional relationships with Takeda, Abbvie, Eli Lilly, and others.
Transcriptomic profiling of phagocytes in the lamina propria of patients with inflammatory bowel disease (IBD) may guide future treatment selection, according to investigators.
Mucosal gut biopsies revealed that phagocytic gene expression correlated with inflammatory states, types of IBD, and responses to therapy, lead author Gillian E. Jacobsen a MD/PhD candidate at the University of Miami and colleagues reported.
In an article in Gastro Hep Advances, the investigators wrote that “lamina propria phagocytes along with epithelial cells represent a first line of defense and play a balancing act between tolerance toward commensal microbes and generation of immune responses toward pathogenic microorganisms. ... Inappropriate responses by lamina propria phagocytes have been linked to IBD.”
To better understand these responses, the researchers collected 111 gut mucosal biopsies from 54 patients with IBD, among whom 59% were taking biologics, 72% had inflammation in at least one biopsy site, and 41% had previously used at least one other biologic. Samples were analyzed to determine cell phenotypes, gene expression, and cytokine responses to in vitro Janus kinase (JAK) inhibitor exposure.
Ms. Jacobsen and colleagues noted that most reports that address the function of phagocytes focus on circulating dendritic cells, monocytes, or monocyte-derived macrophages, rather than on resident phagocyte populations located in the lamina propria. However, these circulating cells “do not reflect intestinal inflammation, or whole tissue biopsies.”
Phagocytes based on CD11b expression and phenotyped CD11b+-enriched cells using flow cytometry were identified. In samples with active inflammation, cells were most often granulocytes (45.5%), followed by macrophages (22.6%) and monocytes (9.4%). Uninflamed samples had a slightly lower proportion of granulocytes (33.6%), about the same proportion of macrophages (22.7%), and a higher rate of B cells (15.6% vs. 9.0%).
Ms. Jacobsen and colleagues highlighted the absolute uptick in granulocytes, including neutrophils.
“Neutrophilic infiltration is a major indicator of IBD activity and may be critically linked to ongoing inflammation,” they wrote. “These data demonstrate that CD11b+ enrichment reflects the inflammatory state of the biopsies.”
The investigators also showed that transcriptional profiles of lamina propria CD11b+ cells differed “greatly” between colon and ileum, which suggested that “the location or cellular environment plays a marked role in determining the gene expression of phagocytes.”
CD11b+ cell gene expression profiles also correlated with ulcerative colitis versus Crohn’s disease, although the researchers noted that these patterns were less pronounced than correlations with inflammatory states
“There are pathways common to inflammation regardless of the IBD type that could be used as markers of inflammation or targets for therapy.”
Comparing colon samples from patients who responded to anti–tumor necrosis factor therapy with those who were refractory to anti-TNF therapy revealed significant associations between response type and 52 differentially expressed genes.
“These genes were mostly immunoglobulin genes up-regulated in the anti–TNF-treated inflamed colon, suggesting that CD11b+ B cells may play a role in medication refractoriness.”
Evaluating inflamed colon and anti-TNF refractory ileum revealed differential expression of OSM, a known marker of TNF-resistant disease, as well as TREM1, a proinflammatory marker. In contrast, NTS genes showed high expression in uninflamed samples on anti-TNF therapy. The researchers noted that these findings “may be used to build precision medicine approaches in IBD.”
Further experiments showed that in vitro exposure of anti-TNF refractory samples to JAK inhibitors resulted in significantly reduced secretion of interleukin-8 and TNF-alpha.
“Our study provides functional data that JAK inhibition with tofacitinib (JAK1/JAK3) or ruxolitinib (JAK1/JAK2) inhibits lipopolysaccharide-induced cytokine production even in TNF-refractory samples,” the researchers wrote. “These data inform the response of patients to JAK inhibitors, including those refractory to other treatments.”
The study was supported by Pfizer, the National Institute of Diabetes and Digestive and Kidney Diseases, the Micky & Madeleine Arison Family Foundation Crohn’s & Colitis Discovery Laboratory, and Martin Kalser Chair in Gastroenterology at the University of Miami. The investigators disclosed additional relationships with Takeda, Abbvie, Eli Lilly, and others.
FROM GASTRO HEP ADVANCES
Reading Chekhov on the Cancer Ward
Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.1 Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.
Short Story Club
Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.4 In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.
Slowing Down
The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.5 The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.
Mirrors and Windows
Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.6 Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.
In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.7 The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.
The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.8 In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.
In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.9 She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.
Exploring the Taboo
A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.10 He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.
Moral Grounding
These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.11 Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.
In another session we read and reflected on “Three Questions” by Leo Tolstoy.12 In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.
Symbols and Metaphors
The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.13 The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.
Problem-solving Guide
A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.14 Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.
Bonding Through Shared Experience
The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.
Conclusions
Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.3 We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.3 We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.
This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.
Acknowledgments
The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.
1. Messias E, Gathright MM, Freeman ES, et al. Differences in burnout prevalence between clinical professionals and biomedical scientists in an academic medical centre: a cross-sectional survey. BMJ Open. 2019;9(2):e023506. doi:10.1136/bmjopen-2018-023506
2. Marchalik D, Rodriguez A, Namath A, et al. The impact of non-medical reading on clinical burnout: a national survey of palliative care providers. Ann Palliat Med. 2019;8(4):428-435. doi:10.21037/apm.2019.05.02
3. West CP, Dyrbye LN, Rabatin JT, et al. Intervention to promote physician well-being, job satisfaction, and professionalism: a randomized clinical trial. JAMA Intern Med. 2014;174(4):527-533. doi:10.1001/jamainternmed.2013.14387
4. Charon R. Narrative medicine: a model for empathy, reflection, profession, and tust. JAMA. 2001;286(15):1897–1902. doi:10.1001/jama.286.15.1897
5. Broyard A. Doctor Talk to Me. August 26, 1990. Accessed September 2021. https://www.nytimes.com/1990/08/26/magazine/doctor-talk-to-me.html
6. Chekhov A. A Doctor’s Visit,. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:50-59.
7. Lahiri J. Interpreter of Maladies. In: Lahiri J. Interpreter of Maladies. Mariner Books;2019.
8. Fitzgerald FS. Babylon Revisited. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:62-81.
9. Hemingway E. Hills like White Elephants. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:108-111.
10. Karmel M. Caves of Lascaux. In: Ofri D, Staff of the Bellavue Literary Review, eds. The Best of the Bellevue Literary Review. Bellevue Literary Press;2008:168-174.
11. Lardner R. The Haircut. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:48-61.
12. Tolstoy L. The Three Questions. Accessed September 2021. https://www.plough.com/en/topics/culture/short-stories/the-three-questions
13. Olsen T. I Stand Here Ironing. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:173-180.
14. Hale N. Those Are as Brothers. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:132-141.
Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.1 Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.
Short Story Club
Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.4 In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.
Slowing Down
The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.5 The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.
Mirrors and Windows
Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.6 Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.
In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.7 The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.
The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.8 In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.
In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.9 She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.
Exploring the Taboo
A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.10 He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.
Moral Grounding
These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.11 Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.
In another session we read and reflected on “Three Questions” by Leo Tolstoy.12 In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.
Symbols and Metaphors
The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.13 The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.
Problem-solving Guide
A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.14 Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.
Bonding Through Shared Experience
The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.
Conclusions
Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.3 We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.3 We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.
This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.
Acknowledgments
The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.
Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.1 Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.
Short Story Club
Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.4 In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.
Slowing Down
The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.5 The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.
Mirrors and Windows
Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.6 Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.
In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.7 The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.
The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.8 In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.
In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.9 She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.
Exploring the Taboo
A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.10 He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.
Moral Grounding
These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.11 Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.
In another session we read and reflected on “Three Questions” by Leo Tolstoy.12 In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.
Symbols and Metaphors
The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.13 The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.
Problem-solving Guide
A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.14 Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.
Bonding Through Shared Experience
The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.
Conclusions
Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.3 We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.3 We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.
This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.
Acknowledgments
The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.
1. Messias E, Gathright MM, Freeman ES, et al. Differences in burnout prevalence between clinical professionals and biomedical scientists in an academic medical centre: a cross-sectional survey. BMJ Open. 2019;9(2):e023506. doi:10.1136/bmjopen-2018-023506
2. Marchalik D, Rodriguez A, Namath A, et al. The impact of non-medical reading on clinical burnout: a national survey of palliative care providers. Ann Palliat Med. 2019;8(4):428-435. doi:10.21037/apm.2019.05.02
3. West CP, Dyrbye LN, Rabatin JT, et al. Intervention to promote physician well-being, job satisfaction, and professionalism: a randomized clinical trial. JAMA Intern Med. 2014;174(4):527-533. doi:10.1001/jamainternmed.2013.14387
4. Charon R. Narrative medicine: a model for empathy, reflection, profession, and tust. JAMA. 2001;286(15):1897–1902. doi:10.1001/jama.286.15.1897
5. Broyard A. Doctor Talk to Me. August 26, 1990. Accessed September 2021. https://www.nytimes.com/1990/08/26/magazine/doctor-talk-to-me.html
6. Chekhov A. A Doctor’s Visit,. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:50-59.
7. Lahiri J. Interpreter of Maladies. In: Lahiri J. Interpreter of Maladies. Mariner Books;2019.
8. Fitzgerald FS. Babylon Revisited. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:62-81.
9. Hemingway E. Hills like White Elephants. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:108-111.
10. Karmel M. Caves of Lascaux. In: Ofri D, Staff of the Bellavue Literary Review, eds. The Best of the Bellevue Literary Review. Bellevue Literary Press;2008:168-174.
11. Lardner R. The Haircut. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:48-61.
12. Tolstoy L. The Three Questions. Accessed September 2021. https://www.plough.com/en/topics/culture/short-stories/the-three-questions
13. Olsen T. I Stand Here Ironing. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:173-180.
14. Hale N. Those Are as Brothers. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:132-141.
1. Messias E, Gathright MM, Freeman ES, et al. Differences in burnout prevalence between clinical professionals and biomedical scientists in an academic medical centre: a cross-sectional survey. BMJ Open. 2019;9(2):e023506. doi:10.1136/bmjopen-2018-023506
2. Marchalik D, Rodriguez A, Namath A, et al. The impact of non-medical reading on clinical burnout: a national survey of palliative care providers. Ann Palliat Med. 2019;8(4):428-435. doi:10.21037/apm.2019.05.02
3. West CP, Dyrbye LN, Rabatin JT, et al. Intervention to promote physician well-being, job satisfaction, and professionalism: a randomized clinical trial. JAMA Intern Med. 2014;174(4):527-533. doi:10.1001/jamainternmed.2013.14387
4. Charon R. Narrative medicine: a model for empathy, reflection, profession, and tust. JAMA. 2001;286(15):1897–1902. doi:10.1001/jama.286.15.1897
5. Broyard A. Doctor Talk to Me. August 26, 1990. Accessed September 2021. https://www.nytimes.com/1990/08/26/magazine/doctor-talk-to-me.html
6. Chekhov A. A Doctor’s Visit,. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:50-59.
7. Lahiri J. Interpreter of Maladies. In: Lahiri J. Interpreter of Maladies. Mariner Books;2019.
8. Fitzgerald FS. Babylon Revisited. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:62-81.
9. Hemingway E. Hills like White Elephants. In: Reynolds R, Stone J, eds. On Doctoring. Simon and Shuster;1995:108-111.
10. Karmel M. Caves of Lascaux. In: Ofri D, Staff of the Bellavue Literary Review, eds. The Best of the Bellevue Literary Review. Bellevue Literary Press;2008:168-174.
11. Lardner R. The Haircut. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:48-61.
12. Tolstoy L. The Three Questions. Accessed September 2021. https://www.plough.com/en/topics/culture/short-stories/the-three-questions
13. Olsen T. I Stand Here Ironing. In Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:173-180.
14. Hale N. Those Are as Brothers. In: Moore L, Pitlor H, eds. 100 Years of the Best American Short Stories. Houghton Mifflin Harcourt;2015:132-141.