I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.

I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.

I write this editorial at the end of June as summer officially begins. Much of the country—my New Mexico home included—is suffering under an unbearable heat wave in which even those without belief pray for rain. Summer for many is associated with vacations, family trips, and happy hours in the swimming pool among other enjoyable activities that provide a welcome and much deserved break from routine and relief from the grind of work and school. In the words of the George Gershwin tune, “Summertime, and the livin’ is easy.”

In stark contrast to this season, where there is more lightness in being, is the heaviness of the news reports about the Department of Veteran Affairs (VA) that have been featured in the media and the federal press. I suspect I am not alone in having a hard time opening those e-mails; feeling once more the weight of failure on the VA and the employees who have dedicated a good part of their careers to its mission. Even for the VA, June has seen an exceptional string of bad press. I ask as you read this column to think about what the adjective bad means in this context. In the conclusion to this column, I will suggest that the meaning is multivalent.

Among the most distressing stories was the USA Today and Boston Globe headline, “Secret VA nursing home ratings hide poor quality of care from the public.”² In an all too predictable sequence, this led justifiably to a cascade of demands from the fifth estate, congressional representatives, the administration, veterans and their families, and watchdog organizations for release of the data, investigation of the allegedly deplorable conditions, and rapid fixes to the problems along with the punishment of the guilty.

As an ethicist I am committed to the principles of transparency and accountability that these entities rightly adjure in the wake of any disclosure of a breach of duty to treat each veteran with the best we have—especially the disabled, elderly, and vulnerable. But I have come to believe that the way in which this cycle of scandal and reaction plays out over and over again in VA facilities across the country, what I call “caring under the microscope,” is actually undermining the righteous goals it seeks to achieve.

I encourage you to try this online. Search for the phrase, “VA under microscope” and see what you get. Briefly read the summary, or the entire story if you have the inclination, and then take a few minutes to reflect on the emotional impact of what you read. Under a microscope is an idiom coined to capture the experience of being the object of close inspection and intense scrutiny. As most everyone knows from their own science education, microscopes magnify images that cannot normally be seen with the human eye, allowing us to observe a more detailed and focused image. The microscope surely helped revolutionize medicine and science. But what effect does such amplified and constant observation have on VA employees?³

For the thousands of staff members who do their job every day with all the empathy and skill, integrity, and dedication they can muster, there is demoralization. Researchers in the health professions describe it as “a feeling state of dejection, hopelessness, and a sense of personal ‘incompetence’ that may be tied to a loss of or threat to one’s own goals or values. It has an existential dimension when beliefs and values about oneself are disconfirmed.”⁴ If you are a nurse assigned to one of VA’s nursing homes, daily striving to ensure patients are clean and comfortable, or a therapist in a continuing living center using all your training to maximize an elder’s mobility and participation in activities, you might well begin to doubt your ability as a professional and question the worth of your work. This is exactly the opposite outcome that the microscopic oversight is intended to attain.

The impact of demoralization on health professionals directly contributes to unprecedented burnout and turnover. Were this not damaging enough, it also has an insidious rippling effect—like contaminated groundwater that poisons where it should be reviving. The humanistic, even spiritual, heart of all the health professions is the relationship between the practitioner and the patient, ideally a relationship of mutual respect and trust. Waves of negative news triggering harsh and unyielding criticism distort even the strongest, purest therapeutic alliances with fear and distrust, just as a microscope not properly focused changes a beautiful image into a blurred muddle.

Worried families of veterans staring at this picture invariably are drawn into the hyper media focus, feeling alarmed and betrayed, even when their loved one may be receiving excellent VA care. In 20 years as a physician and ethicist in VA hospitals, clinics, and community living centers, I know well that bad things happen to good people (both patients and staff). Yet VA patients, families, and staff are seldom offered the wider corrective vision that would note that bad things also happen in other health care institutions and good care is delivered in the VA. Acting Secretary of Veterans Affairs Peter O’Rourke crisply summarized in his response to the nursing home story.⁵

No veteran or any other human being in a VA or any other nursing home should ever be medicated into a zombie state or left alone in pain like those patients reported in the news story. And if the USA Today story improves the care of a single VA patient, then good has been done at least in the short run. Yet we must also take the long view and consider the moral and psychological outcome of prolonged demoralization on the very staff who must carry out the congressional mandates.

In the same time frame as the nursing home scandal, the VA Office of Inspector General also issued a report on the continued understaffing in the VA.⁶ This may be the most concerning aftermath of demoralization. One of my best residents had thought about the VA but in the end made a different choice when he completed his training. When I asked him why he told me, “I am afraid to end up in the newspaper.”

Summer will go by far too quickly. Enjoy it while you can so that with renewed strength we may all search for a better way that the light of truth and heat of power can do what they must while also not withering the spirit of caring that animates the people of the VA.

Are refined and processed carbohydrates particularly fattening? Or is a calorie just a calorie, regardless of whether the source is carbohydrate, protein, or fat?

While the debate continues, David S. Ludwig, MD, PhD, and Cara B. Ebbeling, PhD, argued in a recent clinical review that diet does indeed affect metabolism and body composition.

copyright kikkerdirk/Thinkstock

While evidence from human studies remains limited, animal research findings are consistent with a carbohydrate-insulin model of obesity, according to Dr. Ludwig and Dr. Ebbeling, who are with the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and Harvard Medical School.

The carbohydrate-insulin model holds that eating processed, high–glycemic load carbohydrates causes hormonal changes that promote calorie deposition in fat tissue, aggravate hunger, and reduce energy expenditure, they said in JAMA Internal Medicine.

“The conventional way of thinking assumes that the individual has primary control over their calorie balance, and thus, bases conventional treatment on a target of establishing a negative energy balance – so that is 1,000 variations of the ‘eat less, move more’ recommendation,” Dr. Ludwig said in an interview.

The alternative to that established view has proven controversial. The Endocrine Society, in a recent scientific statement, said diet’s effect on obesity risk is largely explainable by calorie intake, rather than some special adverse effect on internal metabolism or energy expenditure.

“Stated differently, ‘a calorie is a calorie,’ ” the authors of the scientific statement said. “Thus, habitual consumption of highly palatable and energy-dense diets predispose to excess weight gain irrespective of macronutrient content.”

Others have sought to refute the carbohydrate-insulin hypothesis in recent reviews, such as an invited commentary in JAMA Internal Medicine by Kevin D. Hall, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and his coauthors.

“Although it is plausible that variables related to insulin signaling could be involved in obesity pathogenesis, the hypothesis that carbohydrate-stimulated insulin secretion is the primary cause of common obesity via direct effects on adipocytes is difficult to reconcile with current evidence,” Dr. Hall and his coauthors wrote in the commentary (JAMA Intern Med. 2018 Jul 2. doi: 10.1001/jamainternmed.2018.2920).

The conventional calorie balance model is a “straw man” that omits neuroendocrine mechanisms known to regulate homeostasis, added Dr. Hall and his coauthors, stating that accurate models of obesity should include physiological processes resisting weight loss and promoting weight gain.

“They might claim that this is a straw man argument, but I would claim that there is a case of the emperor’s new clothing,” Dr. Ludwig countered in the interview. “They argue that body weight is controlled by biology, and that that’s recognized in the conventional view, but how does that view inform treatment in any way? In the absence of any specific testable hypotheses for why the obesity epidemic has emerged so suddenly, conventional recommendations inevitably resort to advice to ‘eat less and move more.’ ”

Dr. Ludwig and Dr. Ebbeling have both conducted research studies examining the carbohydrate-insulin model, or the view that a high-carbohydrate diet results in postprandial hyperinsulinemia and promotes deposition of calories in adipocytes, leading to weight gain through slowing metabolism, increased hunger, or both.

In a study published in the Lancet, Dr. Ludwig and his coinvestigators found that rats fed a high–glycemic index (GI) diet for 18 weeks had more body fat (97.8 grams vs. 57.3 grams; P = .0152) and less lean body mass versus rats fed a low-GI diet. Rats on the high-GI diet also had greater increases over time in blood glucose and plasma insulin after oral glucose. Similarly, mice on a high-GI diet had nearly twice the body fat of mice on low-GI diet, after 9 weeks of feeding (Lancet. 2004 Aug 28. doi: 10.1016/S0140-6736(04)16937-7).

“There’s no way to explain that finding in view of the conventional view that all calories are alike to the body,” Dr. Ludwig said.

“Contrary to prediction of the conventional model, the inherently lower energy density of low-fat diets does not spontaneously produce sustained weight loss. In fact, several recent meta-analyses found that low-fat diets are inferior to all higher-fat [and thus low-glycemic] comparisons. However, these studies characteristically rely on dietary counseling, a method with limitations for testing mechanistic hypotheses owing to varying levels of noncompliance over the long-term,” Dr. Ludwig and Dr. Ebbeling wrote.

Criticisms that claim to refute the carbohydrate-insulin hypothesis are based in part on misinterpretation of recent feeding studies, according to Dr. Ludwig and Dr. Ebbeling. Multiple studies testing whether or not high–glycemic load meals lead to increased fat storage have reported no meaningful differences between low-fat and low-carbohydrate diets. However, these short-term studies, mostly 2 weeks in duration, preclude definitive findings, according to the review.

That’s because the process of adapting to a high-fat diet after having consumed a high-carbohydrate diet takes weeks, which is a well-recognized phenomenon, Dr. Ludwig said.

“If you put sedentary people into military boot camp and tested their biological state after 6 days, you’d probably find that they were fatigued, weak, and had higher inflammation in their muscles, but clearly, you wouldn’t conclude that fitness training is bad for your health,” he said in the interview. “But yet, these are the sort of data that are being used to ‘falsify’ the carbohydrate-insulin model.

“We acknowledge that there aren’t definitive human data,” he continued, “but the conventional model has failed to both explain the obesity epidemic and control it, and the latest public health data suggests that rates are higher today than ever before, despite 50 years of focusing on calorie balance.”

SOURCE: Ludwig DS et al. JAMA Intern Med. 2018 Jul 2. doi:10.1001/jamainternmed.2018.2933.

Are refined and processed carbohydrates particularly fattening? Or is a calorie just a calorie, regardless of whether the source is carbohydrate, protein, or fat?

While the debate continues, David S. Ludwig, MD, PhD, and Cara B. Ebbeling, PhD, argued in a recent clinical review that diet does indeed affect metabolism and body composition.

copyright kikkerdirk/Thinkstock

While evidence from human studies remains limited, animal research findings are consistent with a carbohydrate-insulin model of obesity, according to Dr. Ludwig and Dr. Ebbeling, who are with the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and Harvard Medical School.

The carbohydrate-insulin model holds that eating processed, high–glycemic load carbohydrates causes hormonal changes that promote calorie deposition in fat tissue, aggravate hunger, and reduce energy expenditure, they said in JAMA Internal Medicine.

“The conventional way of thinking assumes that the individual has primary control over their calorie balance, and thus, bases conventional treatment on a target of establishing a negative energy balance – so that is 1,000 variations of the ‘eat less, move more’ recommendation,” Dr. Ludwig said in an interview.

The alternative to that established view has proven controversial. The Endocrine Society, in a recent scientific statement, said diet’s effect on obesity risk is largely explainable by calorie intake, rather than some special adverse effect on internal metabolism or energy expenditure.

“Stated differently, ‘a calorie is a calorie,’ ” the authors of the scientific statement said. “Thus, habitual consumption of highly palatable and energy-dense diets predispose to excess weight gain irrespective of macronutrient content.”

Others have sought to refute the carbohydrate-insulin hypothesis in recent reviews, such as an invited commentary in JAMA Internal Medicine by Kevin D. Hall, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and his coauthors.

“Although it is plausible that variables related to insulin signaling could be involved in obesity pathogenesis, the hypothesis that carbohydrate-stimulated insulin secretion is the primary cause of common obesity via direct effects on adipocytes is difficult to reconcile with current evidence,” Dr. Hall and his coauthors wrote in the commentary (JAMA Intern Med. 2018 Jul 2. doi: 10.1001/jamainternmed.2018.2920).

The conventional calorie balance model is a “straw man” that omits neuroendocrine mechanisms known to regulate homeostasis, added Dr. Hall and his coauthors, stating that accurate models of obesity should include physiological processes resisting weight loss and promoting weight gain.

“They might claim that this is a straw man argument, but I would claim that there is a case of the emperor’s new clothing,” Dr. Ludwig countered in the interview. “They argue that body weight is controlled by biology, and that that’s recognized in the conventional view, but how does that view inform treatment in any way? In the absence of any specific testable hypotheses for why the obesity epidemic has emerged so suddenly, conventional recommendations inevitably resort to advice to ‘eat less and move more.’ ”

Dr. Ludwig and Dr. Ebbeling have both conducted research studies examining the carbohydrate-insulin model, or the view that a high-carbohydrate diet results in postprandial hyperinsulinemia and promotes deposition of calories in adipocytes, leading to weight gain through slowing metabolism, increased hunger, or both.

In a study published in the Lancet, Dr. Ludwig and his coinvestigators found that rats fed a high–glycemic index (GI) diet for 18 weeks had more body fat (97.8 grams vs. 57.3 grams; P = .0152) and less lean body mass versus rats fed a low-GI diet. Rats on the high-GI diet also had greater increases over time in blood glucose and plasma insulin after oral glucose. Similarly, mice on a high-GI diet had nearly twice the body fat of mice on low-GI diet, after 9 weeks of feeding (Lancet. 2004 Aug 28. doi: 10.1016/S0140-6736(04)16937-7).

“There’s no way to explain that finding in view of the conventional view that all calories are alike to the body,” Dr. Ludwig said.

“Contrary to prediction of the conventional model, the inherently lower energy density of low-fat diets does not spontaneously produce sustained weight loss. In fact, several recent meta-analyses found that low-fat diets are inferior to all higher-fat [and thus low-glycemic] comparisons. However, these studies characteristically rely on dietary counseling, a method with limitations for testing mechanistic hypotheses owing to varying levels of noncompliance over the long-term,” Dr. Ludwig and Dr. Ebbeling wrote.

Criticisms that claim to refute the carbohydrate-insulin hypothesis are based in part on misinterpretation of recent feeding studies, according to Dr. Ludwig and Dr. Ebbeling. Multiple studies testing whether or not high–glycemic load meals lead to increased fat storage have reported no meaningful differences between low-fat and low-carbohydrate diets. However, these short-term studies, mostly 2 weeks in duration, preclude definitive findings, according to the review.

That’s because the process of adapting to a high-fat diet after having consumed a high-carbohydrate diet takes weeks, which is a well-recognized phenomenon, Dr. Ludwig said.

“If you put sedentary people into military boot camp and tested their biological state after 6 days, you’d probably find that they were fatigued, weak, and had higher inflammation in their muscles, but clearly, you wouldn’t conclude that fitness training is bad for your health,” he said in the interview. “But yet, these are the sort of data that are being used to ‘falsify’ the carbohydrate-insulin model.

“We acknowledge that there aren’t definitive human data,” he continued, “but the conventional model has failed to both explain the obesity epidemic and control it, and the latest public health data suggests that rates are higher today than ever before, despite 50 years of focusing on calorie balance.”

SOURCE: Ludwig DS et al. JAMA Intern Med. 2018 Jul 2. doi:10.1001/jamainternmed.2018.2933.

Are refined and processed carbohydrates particularly fattening? Or is a calorie just a calorie, regardless of whether the source is carbohydrate, protein, or fat?

While the debate continues, David S. Ludwig, MD, PhD, and Cara B. Ebbeling, PhD, argued in a recent clinical review that diet does indeed affect metabolism and body composition.

copyright kikkerdirk/Thinkstock

While evidence from human studies remains limited, animal research findings are consistent with a carbohydrate-insulin model of obesity, according to Dr. Ludwig and Dr. Ebbeling, who are with the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and Harvard Medical School.

The carbohydrate-insulin model holds that eating processed, high–glycemic load carbohydrates causes hormonal changes that promote calorie deposition in fat tissue, aggravate hunger, and reduce energy expenditure, they said in JAMA Internal Medicine.

“The conventional way of thinking assumes that the individual has primary control over their calorie balance, and thus, bases conventional treatment on a target of establishing a negative energy balance – so that is 1,000 variations of the ‘eat less, move more’ recommendation,” Dr. Ludwig said in an interview.

The alternative to that established view has proven controversial. The Endocrine Society, in a recent scientific statement, said diet’s effect on obesity risk is largely explainable by calorie intake, rather than some special adverse effect on internal metabolism or energy expenditure.

“Stated differently, ‘a calorie is a calorie,’ ” the authors of the scientific statement said. “Thus, habitual consumption of highly palatable and energy-dense diets predispose to excess weight gain irrespective of macronutrient content.”

Others have sought to refute the carbohydrate-insulin hypothesis in recent reviews, such as an invited commentary in JAMA Internal Medicine by Kevin D. Hall, PhD, of the National Institute of Diabetes and Digestive and Kidney Diseases, and his coauthors.

“Although it is plausible that variables related to insulin signaling could be involved in obesity pathogenesis, the hypothesis that carbohydrate-stimulated insulin secretion is the primary cause of common obesity via direct effects on adipocytes is difficult to reconcile with current evidence,” Dr. Hall and his coauthors wrote in the commentary (JAMA Intern Med. 2018 Jul 2. doi: 10.1001/jamainternmed.2018.2920).

The conventional calorie balance model is a “straw man” that omits neuroendocrine mechanisms known to regulate homeostasis, added Dr. Hall and his coauthors, stating that accurate models of obesity should include physiological processes resisting weight loss and promoting weight gain.

“They might claim that this is a straw man argument, but I would claim that there is a case of the emperor’s new clothing,” Dr. Ludwig countered in the interview. “They argue that body weight is controlled by biology, and that that’s recognized in the conventional view, but how does that view inform treatment in any way? In the absence of any specific testable hypotheses for why the obesity epidemic has emerged so suddenly, conventional recommendations inevitably resort to advice to ‘eat less and move more.’ ”

Dr. Ludwig and Dr. Ebbeling have both conducted research studies examining the carbohydrate-insulin model, or the view that a high-carbohydrate diet results in postprandial hyperinsulinemia and promotes deposition of calories in adipocytes, leading to weight gain through slowing metabolism, increased hunger, or both.

In a study published in the Lancet, Dr. Ludwig and his coinvestigators found that rats fed a high–glycemic index (GI) diet for 18 weeks had more body fat (97.8 grams vs. 57.3 grams; P = .0152) and less lean body mass versus rats fed a low-GI diet. Rats on the high-GI diet also had greater increases over time in blood glucose and plasma insulin after oral glucose. Similarly, mice on a high-GI diet had nearly twice the body fat of mice on low-GI diet, after 9 weeks of feeding (Lancet. 2004 Aug 28. doi: 10.1016/S0140-6736(04)16937-7).

“There’s no way to explain that finding in view of the conventional view that all calories are alike to the body,” Dr. Ludwig said.

“Contrary to prediction of the conventional model, the inherently lower energy density of low-fat diets does not spontaneously produce sustained weight loss. In fact, several recent meta-analyses found that low-fat diets are inferior to all higher-fat [and thus low-glycemic] comparisons. However, these studies characteristically rely on dietary counseling, a method with limitations for testing mechanistic hypotheses owing to varying levels of noncompliance over the long-term,” Dr. Ludwig and Dr. Ebbeling wrote.

Criticisms that claim to refute the carbohydrate-insulin hypothesis are based in part on misinterpretation of recent feeding studies, according to Dr. Ludwig and Dr. Ebbeling. Multiple studies testing whether or not high–glycemic load meals lead to increased fat storage have reported no meaningful differences between low-fat and low-carbohydrate diets. However, these short-term studies, mostly 2 weeks in duration, preclude definitive findings, according to the review.

That’s because the process of adapting to a high-fat diet after having consumed a high-carbohydrate diet takes weeks, which is a well-recognized phenomenon, Dr. Ludwig said.

“If you put sedentary people into military boot camp and tested their biological state after 6 days, you’d probably find that they were fatigued, weak, and had higher inflammation in their muscles, but clearly, you wouldn’t conclude that fitness training is bad for your health,” he said in the interview. “But yet, these are the sort of data that are being used to ‘falsify’ the carbohydrate-insulin model.

“We acknowledge that there aren’t definitive human data,” he continued, “but the conventional model has failed to both explain the obesity epidemic and control it, and the latest public health data suggests that rates are higher today than ever before, despite 50 years of focusing on calorie balance.”

SOURCE: Ludwig DS et al. JAMA Intern Med. 2018 Jul 2. doi:10.1001/jamainternmed.2018.2933.

Researching medical information currently is the third most common use of the Internet in the United States,¹ with the majority of adults using the Web as their first source for health information before seeing a physician.² When assessing health-related information online, resources can be grouped into 4 categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational.³ Access to such a wide range of sources may give readers the opportunity to share personal anecdotes and opinions, thereby serving as a forum for information that essentially cannot be validated. Although such websites may include useful information and cite current literature, in other instances health-related information may be misleading or fabricated.³

In a study evaluating 291 skin conditions and related Google trends, acne, psoriasis, and eczema were among the most burdensome diseases, with acne yielding the highest number of search results.⁴ Results of the study indicated a positive correlation between disease burden and online search interest.⁴ The impact of these online searches and the validity of Google search results are topics worth considering, as more dermatology patients are relying on holistic and nonpharmaceutical approaches to treatment and disease management.⁵ The purpose of this study was to evaluate content on diet and dermatology available on the Internet for acne, psoriasis, and eczema.

Methods

Google searches were performed in December 2017 using the terms diet and acne, diet and psoriasis, and diet and eczema. The first 10 results for each respective search were reviewed for recommendations about which foods to incorporate in the diet and which to avoid. They also were classified according to the following 4 website categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational. The recommendations gathered from the 30 websites were then compared to the current literature assessing the impact of diet on these respective conditions by conducting PubMed searches of articles indexed for MEDLINE using the same terms.

Results

The results of this study are outlined in the eTable.

Acne
Our Google search using the term diet and acne produced 17,500,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 40% (4/10) were educational resources, and 20% (2/10) were promotional websites. Most of the websites advised acne patients to avoid high glycemic index foods (90% [9/10]) and dairy products (90% [9/10]). When discussing which foods to include in the diet, 70% (7/10) of websites recommended that patients incorporate omega-3 fatty acids and antioxidants in the diet.

Research has shown that a low glycemic index diet can lead to a decrease in patients’ acne lesion counts in some instances.^6,7 In a case-controlled study of 2258 patients on a popular weight loss diet that emphasized low glycemic index foods, 87% of participants reported a reduction in acne and 91% reported a decrease in their dosage or number of acne medications.⁷ Still, the exact correlation between acne development and consumption of glycemic index foods has not been confirmed. However, high glycemic index diets have been linked to hyperinsulinemia, indicating that insulin levels may play a role in acne formation.⁸ The majority of other currently available studies evaluated the potential link between dairy consumption and acne. A retrospective analysis of 47,355 women spanning 12 weeks showed a positive link between increased dairy consumption, specifically skim milk, and acne formation. Despite the positive trend, limitations such as recall bias made it difficult to draw a conclusion based on these findings.⁹ However, results of a longitudinal questionnaire-based population study evaluating the impact of dairy consumption on acne in 2489 adolescent patients confirmed a positive correlation.¹⁰ Studies conducted in 2009 and 2011 concluded that milk consumption results in elevated insulinlike growth factor 1 levels, which were linked to comedogenesis.^8,11

Currently, there are well-described mechanisms to explain the association of dairy consumption and glycemic index with acne. Confirming a correlation between acne development and dairy consumption suggests that a dairy-free diet may benefit acne patients.⁵ Other trials indicate that low glycemic index diets are beneficial in treating acne.^6,7 Therefore, some of the recommendations made in our search results may be of merit; however, there is minimal evidence proving the benefits of the other dietary recommendations made in the websites we evaluated.

Psoriasis
Our Google search using the term diet and psoriasis yielded a total of 9,420,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 30% (3/10) were promotional, and 30% (3/10) were educational. Seventy percent (7/10) of websites recommended avoiding alcohol and 60% (6/10) recommended avoiding gluten, with others discouraging consumption of red meat. Most of the websites encouraged patients to consume omega-3 fatty acids and antioxidants, while a few also recommended vitamins A, D, and E, as well as evening primrose oil supplements.

Although current research indicates a positive correlation between excessive alcohol use and psoriasis severity, it is still unclear whether alcohol consumption can be directly linked to the disease.^12-14 Likewise, despite belief that increased oxidative stress likely contributes to inflammation in psoriasis, there is little evidence linking antioxidants to improvement in psoriasis symptoms.¹² However, the current literature is inconsistent regarding the effects of fish oil supplementation on psoriasis.¹² In a randomized double-blind study of 145 patients, there was no significant difference in psoriasis area and severity index scores between a control group and a treatment group receiving fish oil supplementation.¹⁵ In another RCT of 45 participants, those given daily very long-chain omega-3 fatty acid supplements saw no difference in psoriasis symptoms.¹⁵ Despite debate, literature assessing the impact of gluten-free diets has described improvement in psoriasis lesions in patients with celiac-specific antibodies.¹⁶ Although some observational studies described vitamin D supplementation to be beneficial in the treatment of psoriatic lesions, a more recent RCT found no significant difference between control and treatment groups.^17-19

Studies also have revealed that certain eating patterns, such as those associated with the Mediterranean diet that is rich in fruits, vegetables, whole grains, and omega-3 fatty acids may be linked to improved endothelial function scores and reduced C-reactive protein and IL-18levels.^20,21 In a double-blind RCT of 75 patients with plaque psoriasis, mean (SD) psoriasis area and severity index scores decreased by 11.2 (9.8) in a group treated with omega-3 fatty acids compared to 7.5 (8.8) with omega-6 fatty acids (P=.048).²²

Although excessive alcohol use may be linked to psoriasis, there is no conclusive evidence indicating causation, thereby discrediting online claims.^12-14 Research has revealed that gluten-free diets in psoriasis patients with celiac disease may improve psoriasis treatment¹⁶; however, sufficient evidence is lacking for diets low in gluten and high in polyunsaturated fatty acids or antioxidant supplementation. Of the dietary supplements recommended in the search results we reviewed, fish oil appears to be the most promising, but no recommendations can be made based on the current research.

Eczema
Our Google search using the term diet and eczema yielded 1,160,000 results, with 50% (5/10) of websites attributed to self-proclaimed experts, 30% (3/10) to educational websites, and 20% (2/10) to promotional sites. Of the first 10 results, 80% (8/10) recommended that patients with eczema avoid milk/dairy and 50% (5/10) advised to avoid soy and wheat/gluten. Other websites indicated to avoid eggs, nuts, and artificial sweeteners. Patients were encouraged to incorporate omega-3 fatty acids in their diets, and a few sites recommended bananas, coconut oil, olive oil, and various teas.

In a review of 11 studies with a total of 596 participants, supplementation with vitamins D and E, fish oil, olive oil, and linoleic acid was evaluated for the treatment of eczema.²³ Although results indicated modest improvement of eczema severity with supplementation of fish oil, evidence favoring this treatment is limited and unconvincing. Furthermore, some evidence indicates that elimination diets are only appropriate for patients with food allergies.²⁴ In a study evaluating an egg-free and dairy-free diet for eczema patients, only participants with positive egg-specific serum IgE levels saw improvement in disease severity.²³ Even though IgE-mediated food allergies have been reported in 40% of children with moderate eczema, the contribution of these allergies to eczema is questionable.²⁵

There is little evidence in the literature to indicate a definitive correlation between the foods mentioned in the search results we evaluated and the development of eczema; however, for patients with food allergies and eczema, elimination diets may decrease disease severity.^25,26 There is insufficient evidence to suggest a benefit from evening primrose oil or fish oil supplementation, thereby debunking claims found online.

Comment

Although our Google search results included a wide range of sources and information regarding diet and dermatologic conditions such as acne, psoriasis, and eczema, most of the information we found was either unfounded or misleading. Study limitations in the current literature include small sample size, potential recall bias, lack of appropriate controls, incomplete reported results, and the failure to clearly define skin changes.

When considering the accuracy and type of information regarding skin conditions that is available on the Internet, it is important to note that most of the results we reviewed were webpages attributed to self-proclaimed experts. Although educational websites also were included in the search results, whether or not patients prefer or understand the content of such websites is still unknown; therefore, health organizations should consider revising online patient education materials to allow universal comprehension.²⁷

Furthermore, it is important to consider the impact that widespread Internet access may have on the physician-patient relationship. Having access to health-related information online and being able to potentially self-diagnose could delay or deter patients from seeking professional advice or care.³ A study evaluating the impact of online searches on the physician-patient relationship among 175 patients determined that 36.5% of patients gathered information online prior to their consultation with a physician, while 67.3% chose to complement the information given to them by their physician with online resources.²⁸ Based on these statistics, it is important that physicians be up-to-date with Internet discourse to discredit unfounded recommendations. Ultimately, when it comes to diet and dermatology, patients ought to be skeptical of the information currently available on the Internet, given that most of it is unsubstantiated by medical research.

Researching medical information currently is the third most common use of the Internet in the United States,¹ with the majority of adults using the Web as their first source for health information before seeing a physician.² When assessing health-related information online, resources can be grouped into 4 categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational.³ Access to such a wide range of sources may give readers the opportunity to share personal anecdotes and opinions, thereby serving as a forum for information that essentially cannot be validated. Although such websites may include useful information and cite current literature, in other instances health-related information may be misleading or fabricated.³

In a study evaluating 291 skin conditions and related Google trends, acne, psoriasis, and eczema were among the most burdensome diseases, with acne yielding the highest number of search results.⁴ Results of the study indicated a positive correlation between disease burden and online search interest.⁴ The impact of these online searches and the validity of Google search results are topics worth considering, as more dermatology patients are relying on holistic and nonpharmaceutical approaches to treatment and disease management.⁵ The purpose of this study was to evaluate content on diet and dermatology available on the Internet for acne, psoriasis, and eczema.

Methods

Google searches were performed in December 2017 using the terms diet and acne, diet and psoriasis, and diet and eczema. The first 10 results for each respective search were reviewed for recommendations about which foods to incorporate in the diet and which to avoid. They also were classified according to the following 4 website categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational. The recommendations gathered from the 30 websites were then compared to the current literature assessing the impact of diet on these respective conditions by conducting PubMed searches of articles indexed for MEDLINE using the same terms.

Results

The results of this study are outlined in the eTable.

Acne
Our Google search using the term diet and acne produced 17,500,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 40% (4/10) were educational resources, and 20% (2/10) were promotional websites. Most of the websites advised acne patients to avoid high glycemic index foods (90% [9/10]) and dairy products (90% [9/10]). When discussing which foods to include in the diet, 70% (7/10) of websites recommended that patients incorporate omega-3 fatty acids and antioxidants in the diet.

Research has shown that a low glycemic index diet can lead to a decrease in patients’ acne lesion counts in some instances.^6,7 In a case-controlled study of 2258 patients on a popular weight loss diet that emphasized low glycemic index foods, 87% of participants reported a reduction in acne and 91% reported a decrease in their dosage or number of acne medications.⁷ Still, the exact correlation between acne development and consumption of glycemic index foods has not been confirmed. However, high glycemic index diets have been linked to hyperinsulinemia, indicating that insulin levels may play a role in acne formation.⁸ The majority of other currently available studies evaluated the potential link between dairy consumption and acne. A retrospective analysis of 47,355 women spanning 12 weeks showed a positive link between increased dairy consumption, specifically skim milk, and acne formation. Despite the positive trend, limitations such as recall bias made it difficult to draw a conclusion based on these findings.⁹ However, results of a longitudinal questionnaire-based population study evaluating the impact of dairy consumption on acne in 2489 adolescent patients confirmed a positive correlation.¹⁰ Studies conducted in 2009 and 2011 concluded that milk consumption results in elevated insulinlike growth factor 1 levels, which were linked to comedogenesis.^8,11

Currently, there are well-described mechanisms to explain the association of dairy consumption and glycemic index with acne. Confirming a correlation between acne development and dairy consumption suggests that a dairy-free diet may benefit acne patients.⁵ Other trials indicate that low glycemic index diets are beneficial in treating acne.^6,7 Therefore, some of the recommendations made in our search results may be of merit; however, there is minimal evidence proving the benefits of the other dietary recommendations made in the websites we evaluated.

Psoriasis
Our Google search using the term diet and psoriasis yielded a total of 9,420,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 30% (3/10) were promotional, and 30% (3/10) were educational. Seventy percent (7/10) of websites recommended avoiding alcohol and 60% (6/10) recommended avoiding gluten, with others discouraging consumption of red meat. Most of the websites encouraged patients to consume omega-3 fatty acids and antioxidants, while a few also recommended vitamins A, D, and E, as well as evening primrose oil supplements.

Although current research indicates a positive correlation between excessive alcohol use and psoriasis severity, it is still unclear whether alcohol consumption can be directly linked to the disease.^12-14 Likewise, despite belief that increased oxidative stress likely contributes to inflammation in psoriasis, there is little evidence linking antioxidants to improvement in psoriasis symptoms.¹² However, the current literature is inconsistent regarding the effects of fish oil supplementation on psoriasis.¹² In a randomized double-blind study of 145 patients, there was no significant difference in psoriasis area and severity index scores between a control group and a treatment group receiving fish oil supplementation.¹⁵ In another RCT of 45 participants, those given daily very long-chain omega-3 fatty acid supplements saw no difference in psoriasis symptoms.¹⁵ Despite debate, literature assessing the impact of gluten-free diets has described improvement in psoriasis lesions in patients with celiac-specific antibodies.¹⁶ Although some observational studies described vitamin D supplementation to be beneficial in the treatment of psoriatic lesions, a more recent RCT found no significant difference between control and treatment groups.^17-19

Studies also have revealed that certain eating patterns, such as those associated with the Mediterranean diet that is rich in fruits, vegetables, whole grains, and omega-3 fatty acids may be linked to improved endothelial function scores and reduced C-reactive protein and IL-18levels.^20,21 In a double-blind RCT of 75 patients with plaque psoriasis, mean (SD) psoriasis area and severity index scores decreased by 11.2 (9.8) in a group treated with omega-3 fatty acids compared to 7.5 (8.8) with omega-6 fatty acids (P=.048).²²

Although excessive alcohol use may be linked to psoriasis, there is no conclusive evidence indicating causation, thereby discrediting online claims.^12-14 Research has revealed that gluten-free diets in psoriasis patients with celiac disease may improve psoriasis treatment¹⁶; however, sufficient evidence is lacking for diets low in gluten and high in polyunsaturated fatty acids or antioxidant supplementation. Of the dietary supplements recommended in the search results we reviewed, fish oil appears to be the most promising, but no recommendations can be made based on the current research.

Eczema
Our Google search using the term diet and eczema yielded 1,160,000 results, with 50% (5/10) of websites attributed to self-proclaimed experts, 30% (3/10) to educational websites, and 20% (2/10) to promotional sites. Of the first 10 results, 80% (8/10) recommended that patients with eczema avoid milk/dairy and 50% (5/10) advised to avoid soy and wheat/gluten. Other websites indicated to avoid eggs, nuts, and artificial sweeteners. Patients were encouraged to incorporate omega-3 fatty acids in their diets, and a few sites recommended bananas, coconut oil, olive oil, and various teas.

In a review of 11 studies with a total of 596 participants, supplementation with vitamins D and E, fish oil, olive oil, and linoleic acid was evaluated for the treatment of eczema.²³ Although results indicated modest improvement of eczema severity with supplementation of fish oil, evidence favoring this treatment is limited and unconvincing. Furthermore, some evidence indicates that elimination diets are only appropriate for patients with food allergies.²⁴ In a study evaluating an egg-free and dairy-free diet for eczema patients, only participants with positive egg-specific serum IgE levels saw improvement in disease severity.²³ Even though IgE-mediated food allergies have been reported in 40% of children with moderate eczema, the contribution of these allergies to eczema is questionable.²⁵

There is little evidence in the literature to indicate a definitive correlation between the foods mentioned in the search results we evaluated and the development of eczema; however, for patients with food allergies and eczema, elimination diets may decrease disease severity.^25,26 There is insufficient evidence to suggest a benefit from evening primrose oil or fish oil supplementation, thereby debunking claims found online.

Comment

Although our Google search results included a wide range of sources and information regarding diet and dermatologic conditions such as acne, psoriasis, and eczema, most of the information we found was either unfounded or misleading. Study limitations in the current literature include small sample size, potential recall bias, lack of appropriate controls, incomplete reported results, and the failure to clearly define skin changes.

When considering the accuracy and type of information regarding skin conditions that is available on the Internet, it is important to note that most of the results we reviewed were webpages attributed to self-proclaimed experts. Although educational websites also were included in the search results, whether or not patients prefer or understand the content of such websites is still unknown; therefore, health organizations should consider revising online patient education materials to allow universal comprehension.²⁷

Furthermore, it is important to consider the impact that widespread Internet access may have on the physician-patient relationship. Having access to health-related information online and being able to potentially self-diagnose could delay or deter patients from seeking professional advice or care.³ A study evaluating the impact of online searches on the physician-patient relationship among 175 patients determined that 36.5% of patients gathered information online prior to their consultation with a physician, while 67.3% chose to complement the information given to them by their physician with online resources.²⁸ Based on these statistics, it is important that physicians be up-to-date with Internet discourse to discredit unfounded recommendations. Ultimately, when it comes to diet and dermatology, patients ought to be skeptical of the information currently available on the Internet, given that most of it is unsubstantiated by medical research.

Researching medical information currently is the third most common use of the Internet in the United States,¹ with the majority of adults using the Web as their first source for health information before seeing a physician.² When assessing health-related information online, resources can be grouped into 4 categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational.³ Access to such a wide range of sources may give readers the opportunity to share personal anecdotes and opinions, thereby serving as a forum for information that essentially cannot be validated. Although such websites may include useful information and cite current literature, in other instances health-related information may be misleading or fabricated.³

In a study evaluating 291 skin conditions and related Google trends, acne, psoriasis, and eczema were among the most burdensome diseases, with acne yielding the highest number of search results.⁴ Results of the study indicated a positive correlation between disease burden and online search interest.⁴ The impact of these online searches and the validity of Google search results are topics worth considering, as more dermatology patients are relying on holistic and nonpharmaceutical approaches to treatment and disease management.⁵ The purpose of this study was to evaluate content on diet and dermatology available on the Internet for acne, psoriasis, and eczema.

Methods

Google searches were performed in December 2017 using the terms diet and acne, diet and psoriasis, and diet and eczema. The first 10 results for each respective search were reviewed for recommendations about which foods to incorporate in the diet and which to avoid. They also were classified according to the following 4 website categories: (1) those attributed to self-proclaimed experts, (2) promotional, (3) social media, and (4) educational. The recommendations gathered from the 30 websites were then compared to the current literature assessing the impact of diet on these respective conditions by conducting PubMed searches of articles indexed for MEDLINE using the same terms.

Results

The results of this study are outlined in the eTable.

Acne
Our Google search using the term diet and acne produced 17,500,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 40% (4/10) were educational resources, and 20% (2/10) were promotional websites. Most of the websites advised acne patients to avoid high glycemic index foods (90% [9/10]) and dairy products (90% [9/10]). When discussing which foods to include in the diet, 70% (7/10) of websites recommended that patients incorporate omega-3 fatty acids and antioxidants in the diet.

Research has shown that a low glycemic index diet can lead to a decrease in patients’ acne lesion counts in some instances.^6,7 In a case-controlled study of 2258 patients on a popular weight loss diet that emphasized low glycemic index foods, 87% of participants reported a reduction in acne and 91% reported a decrease in their dosage or number of acne medications.⁷ Still, the exact correlation between acne development and consumption of glycemic index foods has not been confirmed. However, high glycemic index diets have been linked to hyperinsulinemia, indicating that insulin levels may play a role in acne formation.⁸ The majority of other currently available studies evaluated the potential link between dairy consumption and acne. A retrospective analysis of 47,355 women spanning 12 weeks showed a positive link between increased dairy consumption, specifically skim milk, and acne formation. Despite the positive trend, limitations such as recall bias made it difficult to draw a conclusion based on these findings.⁹ However, results of a longitudinal questionnaire-based population study evaluating the impact of dairy consumption on acne in 2489 adolescent patients confirmed a positive correlation.¹⁰ Studies conducted in 2009 and 2011 concluded that milk consumption results in elevated insulinlike growth factor 1 levels, which were linked to comedogenesis.^8,11

Currently, there are well-described mechanisms to explain the association of dairy consumption and glycemic index with acne. Confirming a correlation between acne development and dairy consumption suggests that a dairy-free diet may benefit acne patients.⁵ Other trials indicate that low glycemic index diets are beneficial in treating acne.^6,7 Therefore, some of the recommendations made in our search results may be of merit; however, there is minimal evidence proving the benefits of the other dietary recommendations made in the websites we evaluated.

Psoriasis
Our Google search using the term diet and psoriasis yielded a total of 9,420,000 results. Of the first 10 search results, 40% (4/10) were websites attributed to self-proclaimed experts, 30% (3/10) were promotional, and 30% (3/10) were educational. Seventy percent (7/10) of websites recommended avoiding alcohol and 60% (6/10) recommended avoiding gluten, with others discouraging consumption of red meat. Most of the websites encouraged patients to consume omega-3 fatty acids and antioxidants, while a few also recommended vitamins A, D, and E, as well as evening primrose oil supplements.

Although current research indicates a positive correlation between excessive alcohol use and psoriasis severity, it is still unclear whether alcohol consumption can be directly linked to the disease.^12-14 Likewise, despite belief that increased oxidative stress likely contributes to inflammation in psoriasis, there is little evidence linking antioxidants to improvement in psoriasis symptoms.¹² However, the current literature is inconsistent regarding the effects of fish oil supplementation on psoriasis.¹² In a randomized double-blind study of 145 patients, there was no significant difference in psoriasis area and severity index scores between a control group and a treatment group receiving fish oil supplementation.¹⁵ In another RCT of 45 participants, those given daily very long-chain omega-3 fatty acid supplements saw no difference in psoriasis symptoms.¹⁵ Despite debate, literature assessing the impact of gluten-free diets has described improvement in psoriasis lesions in patients with celiac-specific antibodies.¹⁶ Although some observational studies described vitamin D supplementation to be beneficial in the treatment of psoriatic lesions, a more recent RCT found no significant difference between control and treatment groups.^17-19

Studies also have revealed that certain eating patterns, such as those associated with the Mediterranean diet that is rich in fruits, vegetables, whole grains, and omega-3 fatty acids may be linked to improved endothelial function scores and reduced C-reactive protein and IL-18levels.^20,21 In a double-blind RCT of 75 patients with plaque psoriasis, mean (SD) psoriasis area and severity index scores decreased by 11.2 (9.8) in a group treated with omega-3 fatty acids compared to 7.5 (8.8) with omega-6 fatty acids (P=.048).²²

Although excessive alcohol use may be linked to psoriasis, there is no conclusive evidence indicating causation, thereby discrediting online claims.^12-14 Research has revealed that gluten-free diets in psoriasis patients with celiac disease may improve psoriasis treatment¹⁶; however, sufficient evidence is lacking for diets low in gluten and high in polyunsaturated fatty acids or antioxidant supplementation. Of the dietary supplements recommended in the search results we reviewed, fish oil appears to be the most promising, but no recommendations can be made based on the current research.

Eczema
Our Google search using the term diet and eczema yielded 1,160,000 results, with 50% (5/10) of websites attributed to self-proclaimed experts, 30% (3/10) to educational websites, and 20% (2/10) to promotional sites. Of the first 10 results, 80% (8/10) recommended that patients with eczema avoid milk/dairy and 50% (5/10) advised to avoid soy and wheat/gluten. Other websites indicated to avoid eggs, nuts, and artificial sweeteners. Patients were encouraged to incorporate omega-3 fatty acids in their diets, and a few sites recommended bananas, coconut oil, olive oil, and various teas.

In a review of 11 studies with a total of 596 participants, supplementation with vitamins D and E, fish oil, olive oil, and linoleic acid was evaluated for the treatment of eczema.²³ Although results indicated modest improvement of eczema severity with supplementation of fish oil, evidence favoring this treatment is limited and unconvincing. Furthermore, some evidence indicates that elimination diets are only appropriate for patients with food allergies.²⁴ In a study evaluating an egg-free and dairy-free diet for eczema patients, only participants with positive egg-specific serum IgE levels saw improvement in disease severity.²³ Even though IgE-mediated food allergies have been reported in 40% of children with moderate eczema, the contribution of these allergies to eczema is questionable.²⁵

There is little evidence in the literature to indicate a definitive correlation between the foods mentioned in the search results we evaluated and the development of eczema; however, for patients with food allergies and eczema, elimination diets may decrease disease severity.^25,26 There is insufficient evidence to suggest a benefit from evening primrose oil or fish oil supplementation, thereby debunking claims found online.

Comment

Although our Google search results included a wide range of sources and information regarding diet and dermatologic conditions such as acne, psoriasis, and eczema, most of the information we found was either unfounded or misleading. Study limitations in the current literature include small sample size, potential recall bias, lack of appropriate controls, incomplete reported results, and the failure to clearly define skin changes.

When considering the accuracy and type of information regarding skin conditions that is available on the Internet, it is important to note that most of the results we reviewed were webpages attributed to self-proclaimed experts. Although educational websites also were included in the search results, whether or not patients prefer or understand the content of such websites is still unknown; therefore, health organizations should consider revising online patient education materials to allow universal comprehension.²⁷

Furthermore, it is important to consider the impact that widespread Internet access may have on the physician-patient relationship. Having access to health-related information online and being able to potentially self-diagnose could delay or deter patients from seeking professional advice or care.³ A study evaluating the impact of online searches on the physician-patient relationship among 175 patients determined that 36.5% of patients gathered information online prior to their consultation with a physician, while 67.3% chose to complement the information given to them by their physician with online resources.²⁸ Based on these statistics, it is important that physicians be up-to-date with Internet discourse to discredit unfounded recommendations. Ultimately, when it comes to diet and dermatology, patients ought to be skeptical of the information currently available on the Internet, given that most of it is unsubstantiated by medical research.

A study that characterized the occurrence and frequency of thrombocytopenia throughout the course of pregnancy found a significant decline in platelet counts during the course of pregnancy, and significant differences between pregnant and nonpregnant women. However, the study – published in the New England Journal of Medicine – also found that women with pregnancy-related complications were more likely to have platelet counts less than 150,000/mm³, even in the absence of known causes of thrombocytopenia.

Jessica Reese, PhD, and her coinvestigators at the University of Oklahoma, Oklahoma City, used data from pregnant women who delivered at a single site from 2011 to 2014. In all, 4,568 women from the study group had uncomplicated pregnancies, and 2,586 had pregnancy-related complications. To be included in the complicated pregnancy group, women needed a diagnosis of hypertension, diabetes, eclampsia or preeclampsia, or abnormal placentation. Another 197 women had preexisting disorders known to be associated with thrombocytopenia.

For the women with uncomplicated pregnancies, Dr. Reese and her colleagues compared platelet counts with those of nonpregnant women who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012, using a stratified analysis that accounted for age and racial or ethnic background and excluding NHANES participants with cancer, diabetes, or hypertension.

To look at platelet levels across types of pregnancies and in comparison with nonpregnant women, the investigators established three cutpoints, grouping women into those who had a platelet count of at least 150,000/mm³, those with platelet counts less than 100,000/mm³ but at least 80,000/mm³, and those with platelet counts less than 80,000/mm³.

Only 1% of women with uncomplicated pregnancies had platelet counts less than 100,000/mm³ during pregnancy or at delivery, and just 5 women (0.1%) had unexplained platelet counts below 80,000/mm³. Seven more women with platelet counts less than 80,000/mm³ had an identified cause for their thrombocytopenia.

Overall, mean platelet counts were lower for the women with uncomplicated pregnancies during the first trimester than for nonpregnant women (251,000 vs. 273,000/mm³). These values fell throughout pregnancy to a mean of 217,000/mm³ by the time of delivery at a mean gestation of 39.0 weeks (P less than .001 for all time points). However, mean platelet counts rebounded by the time a postpartum value was obtained at a mean 7.1 weeks after delivery, to 264,000/mm³, a value that wasn’t significantly different from the nonpregnant cohort’s platelet counts.

When the investigators looked at mean platelet counts by trimester, they saw no difference between those with uncomplicated and complicated pregnancies until the third trimester. Then, “mean platelet counts decreased at a greater rate among women with pregnancy-related complications,” wrote Dr. Reese and her colleagues; 11.9% of women with complicated pregnancies had platelet counts below 150,000/mm³, while this level was seen in 9.9% of women without complications of pregnancy (P = .01).

At delivery, 2.3% (n = 59) of women with complicated pregnancies had platelet counts below 100,000/mm³, and 31 of these women had counts below 80,000/mm³, representing a significantly higher rate of thrombocytopenia at delivery than seen in the uncomplicated group (P less than .001).

In discussion, Dr. Reese and her coauthors examined the possible mechanisms for decreased levels of circulating platelets during pregnancy. Volume dilution from increased plasma volume is one well-accepted reason. Others include accumulation of platelets within the spleen, which increases in size by about 50% during pregnancy; similarly, the placenta’s circulation is similar to that of the spleen, so platelets may also accumulate there, the authors said. Further support for the placental mechanism comes from the lower average platelet counts for women with twin pregnancies.

The study’s relatively broad definition of pregnancy-related complications may have had the effect of lessening the difference in mean platelet counts between the complicated and uncomplicated pregnancy groups, the investigators acknowledged. Still, their study population had rates of these complications similar to those of the United States population, they said. “Therefore, our data may accurately reflect the platelet counts in women with these pregnancy-related complications,” they noted.

“Severe thrombocytopenia is rare, even in women with pregnancy-related complications,” concluded Dr. Reese and her colleagues. “Our data suggest that, for women with an uncomplicated pregnancy who have a platelet count of less than 100,000/mm³, a cause of thrombocytopenia other than the pregnancy itself should be considered.”

[email protected]

SOURCE: Reese J et al. N Engl J Med. 2018;379:32-43.

A study that characterized the occurrence and frequency of thrombocytopenia throughout the course of pregnancy found a significant decline in platelet counts during the course of pregnancy, and significant differences between pregnant and nonpregnant women. However, the study – published in the New England Journal of Medicine – also found that women with pregnancy-related complications were more likely to have platelet counts less than 150,000/mm³, even in the absence of known causes of thrombocytopenia.

Jessica Reese, PhD, and her coinvestigators at the University of Oklahoma, Oklahoma City, used data from pregnant women who delivered at a single site from 2011 to 2014. In all, 4,568 women from the study group had uncomplicated pregnancies, and 2,586 had pregnancy-related complications. To be included in the complicated pregnancy group, women needed a diagnosis of hypertension, diabetes, eclampsia or preeclampsia, or abnormal placentation. Another 197 women had preexisting disorders known to be associated with thrombocytopenia.

For the women with uncomplicated pregnancies, Dr. Reese and her colleagues compared platelet counts with those of nonpregnant women who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012, using a stratified analysis that accounted for age and racial or ethnic background and excluding NHANES participants with cancer, diabetes, or hypertension.

To look at platelet levels across types of pregnancies and in comparison with nonpregnant women, the investigators established three cutpoints, grouping women into those who had a platelet count of at least 150,000/mm³, those with platelet counts less than 100,000/mm³ but at least 80,000/mm³, and those with platelet counts less than 80,000/mm³.

Only 1% of women with uncomplicated pregnancies had platelet counts less than 100,000/mm³ during pregnancy or at delivery, and just 5 women (0.1%) had unexplained platelet counts below 80,000/mm³. Seven more women with platelet counts less than 80,000/mm³ had an identified cause for their thrombocytopenia.

Overall, mean platelet counts were lower for the women with uncomplicated pregnancies during the first trimester than for nonpregnant women (251,000 vs. 273,000/mm³). These values fell throughout pregnancy to a mean of 217,000/mm³ by the time of delivery at a mean gestation of 39.0 weeks (P less than .001 for all time points). However, mean platelet counts rebounded by the time a postpartum value was obtained at a mean 7.1 weeks after delivery, to 264,000/mm³, a value that wasn’t significantly different from the nonpregnant cohort’s platelet counts.

When the investigators looked at mean platelet counts by trimester, they saw no difference between those with uncomplicated and complicated pregnancies until the third trimester. Then, “mean platelet counts decreased at a greater rate among women with pregnancy-related complications,” wrote Dr. Reese and her colleagues; 11.9% of women with complicated pregnancies had platelet counts below 150,000/mm³, while this level was seen in 9.9% of women without complications of pregnancy (P = .01).

At delivery, 2.3% (n = 59) of women with complicated pregnancies had platelet counts below 100,000/mm³, and 31 of these women had counts below 80,000/mm³, representing a significantly higher rate of thrombocytopenia at delivery than seen in the uncomplicated group (P less than .001).

In discussion, Dr. Reese and her coauthors examined the possible mechanisms for decreased levels of circulating platelets during pregnancy. Volume dilution from increased plasma volume is one well-accepted reason. Others include accumulation of platelets within the spleen, which increases in size by about 50% during pregnancy; similarly, the placenta’s circulation is similar to that of the spleen, so platelets may also accumulate there, the authors said. Further support for the placental mechanism comes from the lower average platelet counts for women with twin pregnancies.

The study’s relatively broad definition of pregnancy-related complications may have had the effect of lessening the difference in mean platelet counts between the complicated and uncomplicated pregnancy groups, the investigators acknowledged. Still, their study population had rates of these complications similar to those of the United States population, they said. “Therefore, our data may accurately reflect the platelet counts in women with these pregnancy-related complications,” they noted.

“Severe thrombocytopenia is rare, even in women with pregnancy-related complications,” concluded Dr. Reese and her colleagues. “Our data suggest that, for women with an uncomplicated pregnancy who have a platelet count of less than 100,000/mm³, a cause of thrombocytopenia other than the pregnancy itself should be considered.”

[email protected]

SOURCE: Reese J et al. N Engl J Med. 2018;379:32-43.

A study that characterized the occurrence and frequency of thrombocytopenia throughout the course of pregnancy found a significant decline in platelet counts during the course of pregnancy, and significant differences between pregnant and nonpregnant women. However, the study – published in the New England Journal of Medicine – also found that women with pregnancy-related complications were more likely to have platelet counts less than 150,000/mm³, even in the absence of known causes of thrombocytopenia.

Jessica Reese, PhD, and her coinvestigators at the University of Oklahoma, Oklahoma City, used data from pregnant women who delivered at a single site from 2011 to 2014. In all, 4,568 women from the study group had uncomplicated pregnancies, and 2,586 had pregnancy-related complications. To be included in the complicated pregnancy group, women needed a diagnosis of hypertension, diabetes, eclampsia or preeclampsia, or abnormal placentation. Another 197 women had preexisting disorders known to be associated with thrombocytopenia.

For the women with uncomplicated pregnancies, Dr. Reese and her colleagues compared platelet counts with those of nonpregnant women who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2012, using a stratified analysis that accounted for age and racial or ethnic background and excluding NHANES participants with cancer, diabetes, or hypertension.

To look at platelet levels across types of pregnancies and in comparison with nonpregnant women, the investigators established three cutpoints, grouping women into those who had a platelet count of at least 150,000/mm³, those with platelet counts less than 100,000/mm³ but at least 80,000/mm³, and those with platelet counts less than 80,000/mm³.

Only 1% of women with uncomplicated pregnancies had platelet counts less than 100,000/mm³ during pregnancy or at delivery, and just 5 women (0.1%) had unexplained platelet counts below 80,000/mm³. Seven more women with platelet counts less than 80,000/mm³ had an identified cause for their thrombocytopenia.

Overall, mean platelet counts were lower for the women with uncomplicated pregnancies during the first trimester than for nonpregnant women (251,000 vs. 273,000/mm³). These values fell throughout pregnancy to a mean of 217,000/mm³ by the time of delivery at a mean gestation of 39.0 weeks (P less than .001 for all time points). However, mean platelet counts rebounded by the time a postpartum value was obtained at a mean 7.1 weeks after delivery, to 264,000/mm³, a value that wasn’t significantly different from the nonpregnant cohort’s platelet counts.

When the investigators looked at mean platelet counts by trimester, they saw no difference between those with uncomplicated and complicated pregnancies until the third trimester. Then, “mean platelet counts decreased at a greater rate among women with pregnancy-related complications,” wrote Dr. Reese and her colleagues; 11.9% of women with complicated pregnancies had platelet counts below 150,000/mm³, while this level was seen in 9.9% of women without complications of pregnancy (P = .01).

At delivery, 2.3% (n = 59) of women with complicated pregnancies had platelet counts below 100,000/mm³, and 31 of these women had counts below 80,000/mm³, representing a significantly higher rate of thrombocytopenia at delivery than seen in the uncomplicated group (P less than .001).

In discussion, Dr. Reese and her coauthors examined the possible mechanisms for decreased levels of circulating platelets during pregnancy. Volume dilution from increased plasma volume is one well-accepted reason. Others include accumulation of platelets within the spleen, which increases in size by about 50% during pregnancy; similarly, the placenta’s circulation is similar to that of the spleen, so platelets may also accumulate there, the authors said. Further support for the placental mechanism comes from the lower average platelet counts for women with twin pregnancies.

The study’s relatively broad definition of pregnancy-related complications may have had the effect of lessening the difference in mean platelet counts between the complicated and uncomplicated pregnancy groups, the investigators acknowledged. Still, their study population had rates of these complications similar to those of the United States population, they said. “Therefore, our data may accurately reflect the platelet counts in women with these pregnancy-related complications,” they noted.

“Severe thrombocytopenia is rare, even in women with pregnancy-related complications,” concluded Dr. Reese and her colleagues. “Our data suggest that, for women with an uncomplicated pregnancy who have a platelet count of less than 100,000/mm³, a cause of thrombocytopenia other than the pregnancy itself should be considered.”

[email protected]

SOURCE: Reese J et al. N Engl J Med. 2018;379:32-43.

SAN DIEGO – Youth and young adults who have transitioned from prescription drug misuse to injection drug use tend to reside in dense social networks, results from a novel study suggest.

“A lot of what we know about the transition from prescription opioids to drug use is from populations that have already transitioned to injection drug use, and we’re asking them retrospectively to tell us about their use,” lead study author Alia Al-Tayyib, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence.

Doug Brunk/MDedge News

[email protected]

SAN DIEGO – Youth and young adults who have transitioned from prescription drug misuse to injection drug use tend to reside in dense social networks, results from a novel study suggest.

“A lot of what we know about the transition from prescription opioids to drug use is from populations that have already transitioned to injection drug use, and we’re asking them retrospectively to tell us about their use,” lead study author Alia Al-Tayyib, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence.

Doug Brunk/MDedge News

[email protected]

SAN DIEGO – Youth and young adults who have transitioned from prescription drug misuse to injection drug use tend to reside in dense social networks, results from a novel study suggest.

“A lot of what we know about the transition from prescription opioids to drug use is from populations that have already transitioned to injection drug use, and we’re asking them retrospectively to tell us about their use,” lead study author Alia Al-Tayyib, PhD, said in an interview at the annual meeting of the College on Problems of Drug Dependence.

Doug Brunk/MDedge News

[email protected]

Knowledge of the potential dangers of mixed martial arts is valuable for Department of Defense (DoD) health care providers as the military continues to implement combatives training into regular military instruction. This case study presents an active-duty service member who developed a spontaneous vertebral artery dissection (sVAD) during mixed martial arts training, which led to a cerebellar stroke.

To the authors’ knowledge this is the first documented case of a sVAD with associated stroke related to a mixed martial arts choke hold. Understanding the diagnosis, management, and prognosis of this condition will remain important as hand-to-hand combat instruction continues to be a part of regular military training.

Case Presentation

A 39-year-old active-duty male without significant past medical history presented to the emergency department (ED) at the San Antonio Military Medical Center in Texas for evaluation of severe vertigo with associated nausea and vomiting. He had participated in a Jiu-Jitsu match the evening prior to his presentation and reported that he was placed in a choke hold within the last 12 seconds of the match. He denied losing consciousness during this hold.

Once released, he attempted to stand and developed sudden onset vertigo with severe nausea, leading to multiple bouts of emesis. He additionally developed a throbbing, left-sided headache radiating down the left side of his neck. While the vertigo resolved within an hour, he continued to experience bouts of nausea and emesis, prompting him to present to the ED for further evaluation. The patient’s past medical history was remarkable only for multiple prior concussions, and his only medication was occasional ibuprofen. He denied the usage of recreational drugs.

Upon presentation to the ED, the patient’s vital signs were 139/93 mm Hg blood pressure, 73 beats per minute heart rate, 16 breaths per minute respiration, 100% oxygen saturation on room air, and 97.7° F temperature. 

The patient demonstrated normal balance and exhibited no nystagmus or limb/truncal ataxia as evaluated with finger-to-nose/heel-to-shin testing and gait exam. Complete blood count, comprehensive metabolic panel, and coagulation panel all demonstrated no abnormalities. 

The patient was admitted to the hospital for symptom control and further monitoring. His headache and nausea were managed with medications, and he began antiplatelet therapy with aspirin 325 mg daily. Given the size of his cerebellar infarction, it was decided that he would be monitored in the hospital for 72 hours for the development of significant cerebellar edema. He remained stable throughout his hospitalization and had only a mild headache at the time of discharge.

The patient was last seen 3 months postinjury with no subjective complaints and a completely normal neurologic exam. The treatment plan for the patient is to continue aspirin for 6 months postinjury at which time a repeat CT will be performed to ensure resolution. He has been counseled to avoid heavy lifting and any activity with potential for sudden movement/force of the neck (grappling/wrestling, chiropractic manipulation, roller coasters, or sit-ups) until the repeat CT has been completed.

Discussion

Spontaneous vertebral artery and carotid artery dissections are collectively referred to as sCADs. Spontaneous cervical artery dissections are a rare condition with a higher incidence of internal carotid dissections than are VADs (1.72 vs 0.97 per 100,000 people).¹ In contrast to the general stroke population, patients with sCADs are typically younger (mean age 45.3 years); and more than half of the patients are male.^1,2

Spontaneous cervical artery dissections are typically characterized by subintimal tears of the vertebral artery leading to the accumulation of an intramural hematoma and creation of a “false lumen” in the arterial wall.³ A sVAD is more often found in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) segments of the vertebral artery than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segments.^3-5 The etiology of these injuries is thought to be minor trauma to the neck in the context of a likely underlying connective tissue disease, though no direct association with a particular disease has been shown.

Biopsy evaluation of the superficial temporal arteries of patients with sCADs have revealed pathologic changes of the media and adventitial layers, including vacuolar degeneration and capillary neoangiogenesis, which are not found in the arteries of control patients.⁵ Although definitive association with a known connective tissue disease is rare, angiographic evidence of fibromuscular dysplasia, a nonspecific marker of connective tissue disease, is noted in as many as 15% to 20% of patients.⁶ Consequently, routine connective tissue disease screening is not recommended in these patients. One study found that about 40% of sCAD patients can recall minor cervical trauma in the preceding month in comparison to only 10% of other patients with stroke, leading to the moniker of “bottoms-up” or “beauty-parlor strokes” for these injuries. The most common mechanisms of minor neck trauma causing sCADs include tennis and golf swings, yoga, and roller-coaster rides.^7,8

Usually symptomatic at presentation, the most frequently encountered sCAD symptoms are head or neck pain (80%), brain ischemia (56%), and Horner syndrome (25%).¹ A study of 161 consecutive patients with internal carotid (n = 135) or vertebral artery (n = 26) dissections revealed that headache was reported by 69% of those with sVADs, and when present, was the initial manifestation in 33%. Headaches typically were ipsilateral to the dissection, located posteriorly in 83% of patients, and lasted an average duration of 72 hours. Neck pain, which was noted in 46% of sVAD patients, was predominantly posterior and ipsilateral in location as well.⁹ Ischemic symptoms of sVAD may include posterior circulation symptoms, such as vertigo, ataxia, diplopia, and leg weakness as well as lateral medullary (Wallenberg) syndrome characterized by dizziness, postural instability, limb hypotonia/ataxia, blurred vision, and nystagmus.

In a study of 169 patients with sCAD, brain ischemia occurred in 77% (131 patients) including 67% (n = 114) with ischemic stroke and 10% (n = 17) with transient ischemic attack. Head and/or neck pain was noted in 88% of those with brain ischemia.⁴ Etiologies for infarction included thromboembolic (85%), hemodynamic (12%), and mixed (3%).¹⁰ Isolated local symptoms are rare with one study of 245 patients with sCAD revealing only 20 (8%) presenting with pain only. Of those with pain only, 6 presented with headache, 2 with neck pain, and 12 with both.¹¹

Diagnosis of sVAD requires a high index of suspicion and is confirmed by diagnostic testing. Previously, invasive angiography was the diagnostic gold standard, but with the improvement in quality of CT and MR angiography, these noninvasive modalities have become the tests of choice. There have been no studies to date revealing a definitive benefit of one modality over the other. A meta-analysis of 25 articles that compared the use of CT and MR angiography for the diagnosis of carotid and VAD revealed similar sensitivity and specificity.¹² In contrast, a study involving 10 patients with confirmed sVAD who had both CT and MR angiographies during evaluation showed more total findings consistent with dissection on CT than with MR angiography when graded by 2 neuroradiologists. Additionally, the neuroradiologists subjectively rated CT angiography as preferential to MR in showing the imaging findings of dissection in 8 of 10 cases of vertebral dissection.¹³

Treatment for sCAD remains heavily debated. The use of IV thrombolysis within the standard time window for acute ischemic stroke is advocated for these patients. A meta-analysis of patients with sCAD vs matched patients with stroke from other causes treated with IV thrombolysis showed no difference in mortality at 3 months (9.0% vs 8.8%) or symptomatic intracranial hemorrhage (3.3% vs 3.0%). Additionally, similar percentages of patients had excellent (30.9% vs 37.4%) and favorable (58.2% vs 52.2%) 3-month functional statuses as expressed by the Modified Rankin Score (mRS).^14,15

Debate remains regarding subacute therapy for sCAD with either antiplatelet or anticoagulant therapy. A randomized study of 250 patients with cervical artery dissection (118 carotid, 132 vertebral) in which 126 patients were assigned to antiplatelet therapy and 124 patients were assigned to anticoagulant therapy showed an overall low rate of recurrent stroke (2%). There was no significant difference in efficacy between the therapy groups with stroke or death occurring in 3 antiplatelet patients and 1 anticoagulated patient. Adverse effects were very low in both groups with no deaths and only 1 major bleed in the anticoagulation group. Of note, stroke rates were lower in this study than prior observational studies.¹⁶

A nonrandomized study of 88 patients with extracranial sCAD showed overall low rates of recurrent ischemic stroke at 3 months with 1/59 (1.7%) in the antiplatelet group and 1/28 (3.6%) in the anticoagulation group (P 17 Given this low overall rate of recurrent stroke in prior studies, a guideline recommendation for antiplatelet or anticoagulant therapy cannot be made at this time.

The overall prognosis for this condition is fair. Functional status and recurrence risk are favorable, with one study finding a mRS score of 1 Additionally, a historic cohort study of 432 patients with first event of sCAD revealed that after a mean follow-up of 31 months, only 4 (0.9%) patients had a recurrent ischemic stroke either due to incomplete recanalization of the artery (n = 2) or recurrent sCAD (n = 2), and only 4 (0.9%) total recurrences of sCAD were report (2 without associated ischemic strokes).¹⁸ Further, a prospective study of 61 patients with confirmed sVAD revealed complete recanalization of 45.9% at 3 months, 62.3% at 6 months, and 63.9% at 12 months, suggesting that recanalization occurs mostly during the initial 6 months. There was no identified association between outcome and complete recanalization with favorable outcomes observed in 55 (90.2%) of patients and no further ischemic symptoms during follow-up.¹⁹

Neck maneuvers have been cited as a more common cause of sCAD in several previous studies. One retrospective study found chiropractic neck manipulation to be the etiology in 12 of 141 patients with CT- or MR- confirmed sCAD.²⁰ As noted previously, to the authors’ knowledge this is the first reported case of a sVAD occurring after a mixed martial arts choke hold. While sports-related strokes are rare, one evaluation of 70 published cases found that 80% were due to sCAD. Commonly associated sports in this study included football, yoga, wrestling, tennis, golf, and swimming.²¹ Grappling-related neck manipulation has been noted as an etiology in a few case reports.

Hyperextension of the neck was deemed to be the etiology in boys aged 11 years and 17 years who developed a sCAD while participating in Judo and backyard wrestling, respectively.^22,23 In the martial arts realm, there is a case report of a 26-year-old male who developed a sVAD after rapid head turning during a solo Kung Fu maneuver as well as a report of a 41-year-old male experiencing a right VAD complicated by a posterior infarction several days after straining his neck during a mixed martial arts competition.^24,25 The patient denied any choke hold or direct blow to the neck.

The present case is different in that it is the first reported case of a sVAD occurring after a submission maneuver. Prior grappling-related sVADs were associated with hyperextension or rapid acceleration/deceleration forces on the neck. Isometric force to the neck is a rarely described mechanism for development of this injury. Although there are isolated and infrequent forensic case reports of carotid dissection with strangulation injuries, the authors believe this is the first documented case of a sVAD attributed to a combatives submission.

In the context of the military health system, it is important to be aware of this potential complication of combatives as instruction in close-quarters combat continues to be an important part of military training.

Knowledge of the potential dangers of mixed martial arts is valuable for Department of Defense (DoD) health care providers as the military continues to implement combatives training into regular military instruction. This case study presents an active-duty service member who developed a spontaneous vertebral artery dissection (sVAD) during mixed martial arts training, which led to a cerebellar stroke.

To the authors’ knowledge this is the first documented case of a sVAD with associated stroke related to a mixed martial arts choke hold. Understanding the diagnosis, management, and prognosis of this condition will remain important as hand-to-hand combat instruction continues to be a part of regular military training.

Case Presentation

A 39-year-old active-duty male without significant past medical history presented to the emergency department (ED) at the San Antonio Military Medical Center in Texas for evaluation of severe vertigo with associated nausea and vomiting. He had participated in a Jiu-Jitsu match the evening prior to his presentation and reported that he was placed in a choke hold within the last 12 seconds of the match. He denied losing consciousness during this hold.

Once released, he attempted to stand and developed sudden onset vertigo with severe nausea, leading to multiple bouts of emesis. He additionally developed a throbbing, left-sided headache radiating down the left side of his neck. While the vertigo resolved within an hour, he continued to experience bouts of nausea and emesis, prompting him to present to the ED for further evaluation. The patient’s past medical history was remarkable only for multiple prior concussions, and his only medication was occasional ibuprofen. He denied the usage of recreational drugs.

Upon presentation to the ED, the patient’s vital signs were 139/93 mm Hg blood pressure, 73 beats per minute heart rate, 16 breaths per minute respiration, 100% oxygen saturation on room air, and 97.7° F temperature. 

The patient demonstrated normal balance and exhibited no nystagmus or limb/truncal ataxia as evaluated with finger-to-nose/heel-to-shin testing and gait exam. Complete blood count, comprehensive metabolic panel, and coagulation panel all demonstrated no abnormalities. 

The patient was admitted to the hospital for symptom control and further monitoring. His headache and nausea were managed with medications, and he began antiplatelet therapy with aspirin 325 mg daily. Given the size of his cerebellar infarction, it was decided that he would be monitored in the hospital for 72 hours for the development of significant cerebellar edema. He remained stable throughout his hospitalization and had only a mild headache at the time of discharge.

The patient was last seen 3 months postinjury with no subjective complaints and a completely normal neurologic exam. The treatment plan for the patient is to continue aspirin for 6 months postinjury at which time a repeat CT will be performed to ensure resolution. He has been counseled to avoid heavy lifting and any activity with potential for sudden movement/force of the neck (grappling/wrestling, chiropractic manipulation, roller coasters, or sit-ups) until the repeat CT has been completed.

Discussion

Spontaneous vertebral artery and carotid artery dissections are collectively referred to as sCADs. Spontaneous cervical artery dissections are a rare condition with a higher incidence of internal carotid dissections than are VADs (1.72 vs 0.97 per 100,000 people).¹ In contrast to the general stroke population, patients with sCADs are typically younger (mean age 45.3 years); and more than half of the patients are male.^1,2

Spontaneous cervical artery dissections are typically characterized by subintimal tears of the vertebral artery leading to the accumulation of an intramural hematoma and creation of a “false lumen” in the arterial wall.³ A sVAD is more often found in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) segments of the vertebral artery than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segments.^3-5 The etiology of these injuries is thought to be minor trauma to the neck in the context of a likely underlying connective tissue disease, though no direct association with a particular disease has been shown.

Biopsy evaluation of the superficial temporal arteries of patients with sCADs have revealed pathologic changes of the media and adventitial layers, including vacuolar degeneration and capillary neoangiogenesis, which are not found in the arteries of control patients.⁵ Although definitive association with a known connective tissue disease is rare, angiographic evidence of fibromuscular dysplasia, a nonspecific marker of connective tissue disease, is noted in as many as 15% to 20% of patients.⁶ Consequently, routine connective tissue disease screening is not recommended in these patients. One study found that about 40% of sCAD patients can recall minor cervical trauma in the preceding month in comparison to only 10% of other patients with stroke, leading to the moniker of “bottoms-up” or “beauty-parlor strokes” for these injuries. The most common mechanisms of minor neck trauma causing sCADs include tennis and golf swings, yoga, and roller-coaster rides.^7,8

Usually symptomatic at presentation, the most frequently encountered sCAD symptoms are head or neck pain (80%), brain ischemia (56%), and Horner syndrome (25%).¹ A study of 161 consecutive patients with internal carotid (n = 135) or vertebral artery (n = 26) dissections revealed that headache was reported by 69% of those with sVADs, and when present, was the initial manifestation in 33%. Headaches typically were ipsilateral to the dissection, located posteriorly in 83% of patients, and lasted an average duration of 72 hours. Neck pain, which was noted in 46% of sVAD patients, was predominantly posterior and ipsilateral in location as well.⁹ Ischemic symptoms of sVAD may include posterior circulation symptoms, such as vertigo, ataxia, diplopia, and leg weakness as well as lateral medullary (Wallenberg) syndrome characterized by dizziness, postural instability, limb hypotonia/ataxia, blurred vision, and nystagmus.

In a study of 169 patients with sCAD, brain ischemia occurred in 77% (131 patients) including 67% (n = 114) with ischemic stroke and 10% (n = 17) with transient ischemic attack. Head and/or neck pain was noted in 88% of those with brain ischemia.⁴ Etiologies for infarction included thromboembolic (85%), hemodynamic (12%), and mixed (3%).¹⁰ Isolated local symptoms are rare with one study of 245 patients with sCAD revealing only 20 (8%) presenting with pain only. Of those with pain only, 6 presented with headache, 2 with neck pain, and 12 with both.¹¹

Diagnosis of sVAD requires a high index of suspicion and is confirmed by diagnostic testing. Previously, invasive angiography was the diagnostic gold standard, but with the improvement in quality of CT and MR angiography, these noninvasive modalities have become the tests of choice. There have been no studies to date revealing a definitive benefit of one modality over the other. A meta-analysis of 25 articles that compared the use of CT and MR angiography for the diagnosis of carotid and VAD revealed similar sensitivity and specificity.¹² In contrast, a study involving 10 patients with confirmed sVAD who had both CT and MR angiographies during evaluation showed more total findings consistent with dissection on CT than with MR angiography when graded by 2 neuroradiologists. Additionally, the neuroradiologists subjectively rated CT angiography as preferential to MR in showing the imaging findings of dissection in 8 of 10 cases of vertebral dissection.¹³

Treatment for sCAD remains heavily debated. The use of IV thrombolysis within the standard time window for acute ischemic stroke is advocated for these patients. A meta-analysis of patients with sCAD vs matched patients with stroke from other causes treated with IV thrombolysis showed no difference in mortality at 3 months (9.0% vs 8.8%) or symptomatic intracranial hemorrhage (3.3% vs 3.0%). Additionally, similar percentages of patients had excellent (30.9% vs 37.4%) and favorable (58.2% vs 52.2%) 3-month functional statuses as expressed by the Modified Rankin Score (mRS).^14,15

Debate remains regarding subacute therapy for sCAD with either antiplatelet or anticoagulant therapy. A randomized study of 250 patients with cervical artery dissection (118 carotid, 132 vertebral) in which 126 patients were assigned to antiplatelet therapy and 124 patients were assigned to anticoagulant therapy showed an overall low rate of recurrent stroke (2%). There was no significant difference in efficacy between the therapy groups with stroke or death occurring in 3 antiplatelet patients and 1 anticoagulated patient. Adverse effects were very low in both groups with no deaths and only 1 major bleed in the anticoagulation group. Of note, stroke rates were lower in this study than prior observational studies.¹⁶

A nonrandomized study of 88 patients with extracranial sCAD showed overall low rates of recurrent ischemic stroke at 3 months with 1/59 (1.7%) in the antiplatelet group and 1/28 (3.6%) in the anticoagulation group (P 17 Given this low overall rate of recurrent stroke in prior studies, a guideline recommendation for antiplatelet or anticoagulant therapy cannot be made at this time.

The overall prognosis for this condition is fair. Functional status and recurrence risk are favorable, with one study finding a mRS score of 1 Additionally, a historic cohort study of 432 patients with first event of sCAD revealed that after a mean follow-up of 31 months, only 4 (0.9%) patients had a recurrent ischemic stroke either due to incomplete recanalization of the artery (n = 2) or recurrent sCAD (n = 2), and only 4 (0.9%) total recurrences of sCAD were report (2 without associated ischemic strokes).¹⁸ Further, a prospective study of 61 patients with confirmed sVAD revealed complete recanalization of 45.9% at 3 months, 62.3% at 6 months, and 63.9% at 12 months, suggesting that recanalization occurs mostly during the initial 6 months. There was no identified association between outcome and complete recanalization with favorable outcomes observed in 55 (90.2%) of patients and no further ischemic symptoms during follow-up.¹⁹

Neck maneuvers have been cited as a more common cause of sCAD in several previous studies. One retrospective study found chiropractic neck manipulation to be the etiology in 12 of 141 patients with CT- or MR- confirmed sCAD.²⁰ As noted previously, to the authors’ knowledge this is the first reported case of a sVAD occurring after a mixed martial arts choke hold. While sports-related strokes are rare, one evaluation of 70 published cases found that 80% were due to sCAD. Commonly associated sports in this study included football, yoga, wrestling, tennis, golf, and swimming.²¹ Grappling-related neck manipulation has been noted as an etiology in a few case reports.

Hyperextension of the neck was deemed to be the etiology in boys aged 11 years and 17 years who developed a sCAD while participating in Judo and backyard wrestling, respectively.^22,23 In the martial arts realm, there is a case report of a 26-year-old male who developed a sVAD after rapid head turning during a solo Kung Fu maneuver as well as a report of a 41-year-old male experiencing a right VAD complicated by a posterior infarction several days after straining his neck during a mixed martial arts competition.^24,25 The patient denied any choke hold or direct blow to the neck.

The present case is different in that it is the first reported case of a sVAD occurring after a submission maneuver. Prior grappling-related sVADs were associated with hyperextension or rapid acceleration/deceleration forces on the neck. Isometric force to the neck is a rarely described mechanism for development of this injury. Although there are isolated and infrequent forensic case reports of carotid dissection with strangulation injuries, the authors believe this is the first documented case of a sVAD attributed to a combatives submission.

In the context of the military health system, it is important to be aware of this potential complication of combatives as instruction in close-quarters combat continues to be an important part of military training.

Knowledge of the potential dangers of mixed martial arts is valuable for Department of Defense (DoD) health care providers as the military continues to implement combatives training into regular military instruction. This case study presents an active-duty service member who developed a spontaneous vertebral artery dissection (sVAD) during mixed martial arts training, which led to a cerebellar stroke.

To the authors’ knowledge this is the first documented case of a sVAD with associated stroke related to a mixed martial arts choke hold. Understanding the diagnosis, management, and prognosis of this condition will remain important as hand-to-hand combat instruction continues to be a part of regular military training.

Case Presentation

A 39-year-old active-duty male without significant past medical history presented to the emergency department (ED) at the San Antonio Military Medical Center in Texas for evaluation of severe vertigo with associated nausea and vomiting. He had participated in a Jiu-Jitsu match the evening prior to his presentation and reported that he was placed in a choke hold within the last 12 seconds of the match. He denied losing consciousness during this hold.

Once released, he attempted to stand and developed sudden onset vertigo with severe nausea, leading to multiple bouts of emesis. He additionally developed a throbbing, left-sided headache radiating down the left side of his neck. While the vertigo resolved within an hour, he continued to experience bouts of nausea and emesis, prompting him to present to the ED for further evaluation. The patient’s past medical history was remarkable only for multiple prior concussions, and his only medication was occasional ibuprofen. He denied the usage of recreational drugs.

Upon presentation to the ED, the patient’s vital signs were 139/93 mm Hg blood pressure, 73 beats per minute heart rate, 16 breaths per minute respiration, 100% oxygen saturation on room air, and 97.7° F temperature. 

The patient demonstrated normal balance and exhibited no nystagmus or limb/truncal ataxia as evaluated with finger-to-nose/heel-to-shin testing and gait exam. Complete blood count, comprehensive metabolic panel, and coagulation panel all demonstrated no abnormalities. 

The patient was admitted to the hospital for symptom control and further monitoring. His headache and nausea were managed with medications, and he began antiplatelet therapy with aspirin 325 mg daily. Given the size of his cerebellar infarction, it was decided that he would be monitored in the hospital for 72 hours for the development of significant cerebellar edema. He remained stable throughout his hospitalization and had only a mild headache at the time of discharge.

The patient was last seen 3 months postinjury with no subjective complaints and a completely normal neurologic exam. The treatment plan for the patient is to continue aspirin for 6 months postinjury at which time a repeat CT will be performed to ensure resolution. He has been counseled to avoid heavy lifting and any activity with potential for sudden movement/force of the neck (grappling/wrestling, chiropractic manipulation, roller coasters, or sit-ups) until the repeat CT has been completed.

Discussion

Spontaneous vertebral artery and carotid artery dissections are collectively referred to as sCADs. Spontaneous cervical artery dissections are a rare condition with a higher incidence of internal carotid dissections than are VADs (1.72 vs 0.97 per 100,000 people).¹ In contrast to the general stroke population, patients with sCADs are typically younger (mean age 45.3 years); and more than half of the patients are male.^1,2

Spontaneous cervical artery dissections are typically characterized by subintimal tears of the vertebral artery leading to the accumulation of an intramural hematoma and creation of a “false lumen” in the arterial wall.³ A sVAD is more often found in the pars transversaria (V2; 35%) or atlas loop (V3; 34%) segments of the vertebral artery than in the prevertebral (V1; 20%) or intracranial (V4; 11%) segments.^3-5 The etiology of these injuries is thought to be minor trauma to the neck in the context of a likely underlying connective tissue disease, though no direct association with a particular disease has been shown.

Biopsy evaluation of the superficial temporal arteries of patients with sCADs have revealed pathologic changes of the media and adventitial layers, including vacuolar degeneration and capillary neoangiogenesis, which are not found in the arteries of control patients.⁵ Although definitive association with a known connective tissue disease is rare, angiographic evidence of fibromuscular dysplasia, a nonspecific marker of connective tissue disease, is noted in as many as 15% to 20% of patients.⁶ Consequently, routine connective tissue disease screening is not recommended in these patients. One study found that about 40% of sCAD patients can recall minor cervical trauma in the preceding month in comparison to only 10% of other patients with stroke, leading to the moniker of “bottoms-up” or “beauty-parlor strokes” for these injuries. The most common mechanisms of minor neck trauma causing sCADs include tennis and golf swings, yoga, and roller-coaster rides.^7,8

Usually symptomatic at presentation, the most frequently encountered sCAD symptoms are head or neck pain (80%), brain ischemia (56%), and Horner syndrome (25%).¹ A study of 161 consecutive patients with internal carotid (n = 135) or vertebral artery (n = 26) dissections revealed that headache was reported by 69% of those with sVADs, and when present, was the initial manifestation in 33%. Headaches typically were ipsilateral to the dissection, located posteriorly in 83% of patients, and lasted an average duration of 72 hours. Neck pain, which was noted in 46% of sVAD patients, was predominantly posterior and ipsilateral in location as well.⁹ Ischemic symptoms of sVAD may include posterior circulation symptoms, such as vertigo, ataxia, diplopia, and leg weakness as well as lateral medullary (Wallenberg) syndrome characterized by dizziness, postural instability, limb hypotonia/ataxia, blurred vision, and nystagmus.

In a study of 169 patients with sCAD, brain ischemia occurred in 77% (131 patients) including 67% (n = 114) with ischemic stroke and 10% (n = 17) with transient ischemic attack. Head and/or neck pain was noted in 88% of those with brain ischemia.⁴ Etiologies for infarction included thromboembolic (85%), hemodynamic (12%), and mixed (3%).¹⁰ Isolated local symptoms are rare with one study of 245 patients with sCAD revealing only 20 (8%) presenting with pain only. Of those with pain only, 6 presented with headache, 2 with neck pain, and 12 with both.¹¹

Diagnosis of sVAD requires a high index of suspicion and is confirmed by diagnostic testing. Previously, invasive angiography was the diagnostic gold standard, but with the improvement in quality of CT and MR angiography, these noninvasive modalities have become the tests of choice. There have been no studies to date revealing a definitive benefit of one modality over the other. A meta-analysis of 25 articles that compared the use of CT and MR angiography for the diagnosis of carotid and VAD revealed similar sensitivity and specificity.¹² In contrast, a study involving 10 patients with confirmed sVAD who had both CT and MR angiographies during evaluation showed more total findings consistent with dissection on CT than with MR angiography when graded by 2 neuroradiologists. Additionally, the neuroradiologists subjectively rated CT angiography as preferential to MR in showing the imaging findings of dissection in 8 of 10 cases of vertebral dissection.¹³

Treatment for sCAD remains heavily debated. The use of IV thrombolysis within the standard time window for acute ischemic stroke is advocated for these patients. A meta-analysis of patients with sCAD vs matched patients with stroke from other causes treated with IV thrombolysis showed no difference in mortality at 3 months (9.0% vs 8.8%) or symptomatic intracranial hemorrhage (3.3% vs 3.0%). Additionally, similar percentages of patients had excellent (30.9% vs 37.4%) and favorable (58.2% vs 52.2%) 3-month functional statuses as expressed by the Modified Rankin Score (mRS).^14,15

Debate remains regarding subacute therapy for sCAD with either antiplatelet or anticoagulant therapy. A randomized study of 250 patients with cervical artery dissection (118 carotid, 132 vertebral) in which 126 patients were assigned to antiplatelet therapy and 124 patients were assigned to anticoagulant therapy showed an overall low rate of recurrent stroke (2%). There was no significant difference in efficacy between the therapy groups with stroke or death occurring in 3 antiplatelet patients and 1 anticoagulated patient. Adverse effects were very low in both groups with no deaths and only 1 major bleed in the anticoagulation group. Of note, stroke rates were lower in this study than prior observational studies.¹⁶

A nonrandomized study of 88 patients with extracranial sCAD showed overall low rates of recurrent ischemic stroke at 3 months with 1/59 (1.7%) in the antiplatelet group and 1/28 (3.6%) in the anticoagulation group (P 17 Given this low overall rate of recurrent stroke in prior studies, a guideline recommendation for antiplatelet or anticoagulant therapy cannot be made at this time.

The overall prognosis for this condition is fair. Functional status and recurrence risk are favorable, with one study finding a mRS score of 1 Additionally, a historic cohort study of 432 patients with first event of sCAD revealed that after a mean follow-up of 31 months, only 4 (0.9%) patients had a recurrent ischemic stroke either due to incomplete recanalization of the artery (n = 2) or recurrent sCAD (n = 2), and only 4 (0.9%) total recurrences of sCAD were report (2 without associated ischemic strokes).¹⁸ Further, a prospective study of 61 patients with confirmed sVAD revealed complete recanalization of 45.9% at 3 months, 62.3% at 6 months, and 63.9% at 12 months, suggesting that recanalization occurs mostly during the initial 6 months. There was no identified association between outcome and complete recanalization with favorable outcomes observed in 55 (90.2%) of patients and no further ischemic symptoms during follow-up.¹⁹

Neck maneuvers have been cited as a more common cause of sCAD in several previous studies. One retrospective study found chiropractic neck manipulation to be the etiology in 12 of 141 patients with CT- or MR- confirmed sCAD.²⁰ As noted previously, to the authors’ knowledge this is the first reported case of a sVAD occurring after a mixed martial arts choke hold. While sports-related strokes are rare, one evaluation of 70 published cases found that 80% were due to sCAD. Commonly associated sports in this study included football, yoga, wrestling, tennis, golf, and swimming.²¹ Grappling-related neck manipulation has been noted as an etiology in a few case reports.

Hyperextension of the neck was deemed to be the etiology in boys aged 11 years and 17 years who developed a sCAD while participating in Judo and backyard wrestling, respectively.^22,23 In the martial arts realm, there is a case report of a 26-year-old male who developed a sVAD after rapid head turning during a solo Kung Fu maneuver as well as a report of a 41-year-old male experiencing a right VAD complicated by a posterior infarction several days after straining his neck during a mixed martial arts competition.^24,25 The patient denied any choke hold or direct blow to the neck.

The present case is different in that it is the first reported case of a sVAD occurring after a submission maneuver. Prior grappling-related sVADs were associated with hyperextension or rapid acceleration/deceleration forces on the neck. Isometric force to the neck is a rarely described mechanism for development of this injury. Although there are isolated and infrequent forensic case reports of carotid dissection with strangulation injuries, the authors believe this is the first documented case of a sVAD attributed to a combatives submission.

In the context of the military health system, it is important to be aware of this potential complication of combatives as instruction in close-quarters combat continues to be an important part of military training.

Bristol Myers Squibb

Real-world data suggest that apixaban poses a lower risk of bleeding than warfarin, but patients who receive lower doses of apixaban have an increased risk of all-cause mortality.

Compared to warfarin, apixaban was associated with a decreased risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding in certain patients.

Dabigatran and rivaroxaban were associated with a decreased risk of intracranial bleeding for certain patients, compared to warfarin.

However, patients who received rivaroxaban or lower doses of apixaban had an increased risk of all-cause mortality, compared to patients who received warfarin.

Yana Vinogradova, PhD, of University of Nottingham in the UK, and her colleagues reported these results in The BMJ.

The researchers set out to investigate the risks and benefits associated with apixaban, dabigatran, and rivaroxaban compared with warfarin in patients with and without atrial fibrillation (AF).

Using data from 2 large UK primary care databases, the researchers identified 196,061 patients who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016.

There were 132,231 patients taking warfarin, 7744 on dabigatran, 37,863 on rivaroxaban, and 18,223 on apixaban.

Slightly more than half of patients (53%, n=103,270) were diagnosed with AF, and 47% (n=92,791) were prescribed anticoagulants for other conditions.

When compared to warfarin in patients with AF, apixaban was associated with a decreased risk of:

• Major bleeding—adjusted hazard ratio [aHR]=0.66
• Intracranial bleeding—aHR=0.40.

In patients without AF, apixaban was associated with a decreased risk of:

• Major bleeding—aHR=0.60
• Any gastrointestinal bleeding—aHR=0.55
• Upper gastrointestinal bleeding—aHR=0.55.

In patients with AF, dabigatran was associated with a decreased risk of intracranial bleeding—aHR=0.45—compared to warfarin.

In patients without AF, rivaroxaban was associated with a decreased risk of intracranial bleeding—aHR=0.54—compared to warfarin.

Compared to patients taking warfarin, there was an increased risk of all-cause mortality for patients:

• With AF taking rivaroxaban—aHR=1.19
• Without AF taking rivaroxaban— aHR=1.51
• With AF taking lower doses of apixaban—aHR=1.27
• Without AF taking lower doses of apixaban—aHR=1.34.

The researchers said the increased risk of all-cause mortality in these patients may reflect the fact that patients taking warfarin are monitored more closely, or it may be related to underlying conditions.

The team did point out that this is an observational study, so no firm conclusions can be drawn about cause and effect. They also outlined some limitations, such as possible misclassification due to patients not taking their medication.

Nevertheless, the researchers concluded that “the risk of major bleeding is lower in apixaban users, regardless of the reason for prescribing, appearing to show apixaban to be the safest drug.”

Bristol Myers Squibb

Real-world data suggest that apixaban poses a lower risk of bleeding than warfarin, but patients who receive lower doses of apixaban have an increased risk of all-cause mortality.

Compared to warfarin, apixaban was associated with a decreased risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding in certain patients.

Dabigatran and rivaroxaban were associated with a decreased risk of intracranial bleeding for certain patients, compared to warfarin.

However, patients who received rivaroxaban or lower doses of apixaban had an increased risk of all-cause mortality, compared to patients who received warfarin.

Yana Vinogradova, PhD, of University of Nottingham in the UK, and her colleagues reported these results in The BMJ.

The researchers set out to investigate the risks and benefits associated with apixaban, dabigatran, and rivaroxaban compared with warfarin in patients with and without atrial fibrillation (AF).

Using data from 2 large UK primary care databases, the researchers identified 196,061 patients who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016.

There were 132,231 patients taking warfarin, 7744 on dabigatran, 37,863 on rivaroxaban, and 18,223 on apixaban.

Slightly more than half of patients (53%, n=103,270) were diagnosed with AF, and 47% (n=92,791) were prescribed anticoagulants for other conditions.

When compared to warfarin in patients with AF, apixaban was associated with a decreased risk of:

• Major bleeding—adjusted hazard ratio [aHR]=0.66
• Intracranial bleeding—aHR=0.40.

In patients without AF, apixaban was associated with a decreased risk of:

• Major bleeding—aHR=0.60
• Any gastrointestinal bleeding—aHR=0.55
• Upper gastrointestinal bleeding—aHR=0.55.

In patients with AF, dabigatran was associated with a decreased risk of intracranial bleeding—aHR=0.45—compared to warfarin.

In patients without AF, rivaroxaban was associated with a decreased risk of intracranial bleeding—aHR=0.54—compared to warfarin.

Compared to patients taking warfarin, there was an increased risk of all-cause mortality for patients:

• With AF taking rivaroxaban—aHR=1.19
• Without AF taking rivaroxaban— aHR=1.51
• With AF taking lower doses of apixaban—aHR=1.27
• Without AF taking lower doses of apixaban—aHR=1.34.

The researchers said the increased risk of all-cause mortality in these patients may reflect the fact that patients taking warfarin are monitored more closely, or it may be related to underlying conditions.

The team did point out that this is an observational study, so no firm conclusions can be drawn about cause and effect. They also outlined some limitations, such as possible misclassification due to patients not taking their medication.

Nevertheless, the researchers concluded that “the risk of major bleeding is lower in apixaban users, regardless of the reason for prescribing, appearing to show apixaban to be the safest drug.”

Bristol Myers Squibb

Real-world data suggest that apixaban poses a lower risk of bleeding than warfarin, but patients who receive lower doses of apixaban have an increased risk of all-cause mortality.

Compared to warfarin, apixaban was associated with a decreased risk of major bleeding, intracranial bleeding, and gastrointestinal bleeding in certain patients.

Dabigatran and rivaroxaban were associated with a decreased risk of intracranial bleeding for certain patients, compared to warfarin.

However, patients who received rivaroxaban or lower doses of apixaban had an increased risk of all-cause mortality, compared to patients who received warfarin.

Yana Vinogradova, PhD, of University of Nottingham in the UK, and her colleagues reported these results in The BMJ.

The researchers set out to investigate the risks and benefits associated with apixaban, dabigatran, and rivaroxaban compared with warfarin in patients with and without atrial fibrillation (AF).

Using data from 2 large UK primary care databases, the researchers identified 196,061 patients who started or restarted anticoagulants (after more than a 12-month gap) between 2011 and 2016.

There were 132,231 patients taking warfarin, 7744 on dabigatran, 37,863 on rivaroxaban, and 18,223 on apixaban.

Slightly more than half of patients (53%, n=103,270) were diagnosed with AF, and 47% (n=92,791) were prescribed anticoagulants for other conditions.

When compared to warfarin in patients with AF, apixaban was associated with a decreased risk of:

• Major bleeding—adjusted hazard ratio [aHR]=0.66
• Intracranial bleeding—aHR=0.40.

In patients without AF, apixaban was associated with a decreased risk of:

• Major bleeding—aHR=0.60
• Any gastrointestinal bleeding—aHR=0.55
• Upper gastrointestinal bleeding—aHR=0.55.

In patients with AF, dabigatran was associated with a decreased risk of intracranial bleeding—aHR=0.45—compared to warfarin.

In patients without AF, rivaroxaban was associated with a decreased risk of intracranial bleeding—aHR=0.54—compared to warfarin.

Compared to patients taking warfarin, there was an increased risk of all-cause mortality for patients:

• With AF taking rivaroxaban—aHR=1.19
• Without AF taking rivaroxaban— aHR=1.51
• With AF taking lower doses of apixaban—aHR=1.27
• Without AF taking lower doses of apixaban—aHR=1.34.

The researchers said the increased risk of all-cause mortality in these patients may reflect the fact that patients taking warfarin are monitored more closely, or it may be related to underlying conditions.

The team did point out that this is an observational study, so no firm conclusions can be drawn about cause and effect. They also outlined some limitations, such as possible misclassification due to patients not taking their medication.

Nevertheless, the researchers concluded that “the risk of major bleeding is lower in apixaban users, regardless of the reason for prescribing, appearing to show apixaban to be the safest drug.”

Micrograph showing myelofibrosis

New research indicates that JAK inhibitors may increase the risk of lymphoma in patients with myelofibrosis (MF).

The patients studied had a 15- to 25-fold higher risk of developing B-cell lymphoma if they received treatment with JAK inhibitors.

The researchers speculate that screening MF patients for a pre-existing B-cell clone before starting JAK inhibitor therapy may help prevent lymphoma development.

Heinz Gisslinger, MD, of the Medical University of Vienna in Austria, and his colleagues conducted this research and reported the findings in Blood.

“[W]e started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment,” Dr Gisslinger said.

Therefore, he and his colleagues assessed 626 patients receiving treatment for myeloproliferative neoplasms (MPNs) at the Medical University of Vienna.

The incidence of B-cell lymphoma was 5.8% (4/69) in patients treated with JAK inhibitors and 0.36% (2/557) in patients who did not receive JAK inhibitors. That amounts to a 16-fold increased risk of lymphoma in patients receiving JAK inhibitors.

When the researchers analyzed only patients with primary MF (n=216), the increased risk of B-cell lymphoma was even greater. The incidence of lymphoma was 9.68% (3/31) in patients treated with JAK inhibitors and 0.54% (1/185) in patients who did not receive JAK inhibitors.

That corresponds to a 19-fold increased risk of B-cell lymphoma in primary MF patients treated with JAK inhibitors. When the researchers adjusted for age, there was a 21-fold greater risk. When they adjusted for sex, the risk was 25 times higher.

In a second cohort of 929 MPN patients, the incidence of B-cell lymphoma was 3.51% (2/57) in patients who received JAK inhibitors and 0.23% (2/872) in patients who did not. This corresponds to a 15-fold increased risk of lymphoma in the JAK inhibitor recipients.

Lymphoma cases

In all, there were 6 patients who developed lymphoma after JAK inhibitor treatment. Five developed diffuse large B-cell lymphoma, and 1 had high-grade B-cell lymphoma not otherwise specified.

Four of the patients had primary MF, 1 had post-polycythemia vera MF, and 1 had post-essential thrombocythemia (ET) MF. Five patients had a JAK2V617F mutation, and 1 (the post-ET MF patient) had a CALR mutation.

All 6 patients had received treatment with ruxolitinib. One patient also received fedratinib.

B-cell clone

The researchers studied bone marrow samples from 54 of the 69 patients treated with JAK inhibitors in the first cohort. The team found a pre-existing B-cell clone in 3 of the 4 patients who developed lymphoma. Further investigation suggested this was the clone that later transformed into lymphoma.

The researchers also found an association between JAK inhibition and an increased frequency of aggressive B-cell lymphomas in mouse models.

“By replicating this link between this B-cell clone and aggressive lymphoma, we hope to speed the discovery of an alternative therapy for myelofibrosis,” said study author Veronica Sexl, MD, of the University of Veterinary Medicine in Vienna. “These findings are going to be valuable in clinical care.”

“We determined that patients with this pre-existing B-cell clone in their bone marrow are most at risk for developing aggressive lymphoma,” added study author Ulrich Jäger, MD, of the Medical University of Vienna.

“We also know that up to 16% of people with myelofibrosis have immunoglobulin gene rearrangements like this B-cell clone. Therefore, our findings suggest that all patients with myelofibrosis should be tested for such gene rearrangements before prescribing JAK inhibitors to treat their disease.”

Micrograph showing myelofibrosis

New research indicates that JAK inhibitors may increase the risk of lymphoma in patients with myelofibrosis (MF).

The patients studied had a 15- to 25-fold higher risk of developing B-cell lymphoma if they received treatment with JAK inhibitors.

The researchers speculate that screening MF patients for a pre-existing B-cell clone before starting JAK inhibitor therapy may help prevent lymphoma development.

Heinz Gisslinger, MD, of the Medical University of Vienna in Austria, and his colleagues conducted this research and reported the findings in Blood.

“[W]e started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment,” Dr Gisslinger said.

Therefore, he and his colleagues assessed 626 patients receiving treatment for myeloproliferative neoplasms (MPNs) at the Medical University of Vienna.

The incidence of B-cell lymphoma was 5.8% (4/69) in patients treated with JAK inhibitors and 0.36% (2/557) in patients who did not receive JAK inhibitors. That amounts to a 16-fold increased risk of lymphoma in patients receiving JAK inhibitors.

When the researchers analyzed only patients with primary MF (n=216), the increased risk of B-cell lymphoma was even greater. The incidence of lymphoma was 9.68% (3/31) in patients treated with JAK inhibitors and 0.54% (1/185) in patients who did not receive JAK inhibitors.

That corresponds to a 19-fold increased risk of B-cell lymphoma in primary MF patients treated with JAK inhibitors. When the researchers adjusted for age, there was a 21-fold greater risk. When they adjusted for sex, the risk was 25 times higher.

In a second cohort of 929 MPN patients, the incidence of B-cell lymphoma was 3.51% (2/57) in patients who received JAK inhibitors and 0.23% (2/872) in patients who did not. This corresponds to a 15-fold increased risk of lymphoma in the JAK inhibitor recipients.

Lymphoma cases

In all, there were 6 patients who developed lymphoma after JAK inhibitor treatment. Five developed diffuse large B-cell lymphoma, and 1 had high-grade B-cell lymphoma not otherwise specified.

Four of the patients had primary MF, 1 had post-polycythemia vera MF, and 1 had post-essential thrombocythemia (ET) MF. Five patients had a JAK2V617F mutation, and 1 (the post-ET MF patient) had a CALR mutation.

All 6 patients had received treatment with ruxolitinib. One patient also received fedratinib.

B-cell clone

The researchers studied bone marrow samples from 54 of the 69 patients treated with JAK inhibitors in the first cohort. The team found a pre-existing B-cell clone in 3 of the 4 patients who developed lymphoma. Further investigation suggested this was the clone that later transformed into lymphoma.

The researchers also found an association between JAK inhibition and an increased frequency of aggressive B-cell lymphomas in mouse models.

“By replicating this link between this B-cell clone and aggressive lymphoma, we hope to speed the discovery of an alternative therapy for myelofibrosis,” said study author Veronica Sexl, MD, of the University of Veterinary Medicine in Vienna. “These findings are going to be valuable in clinical care.”

“We determined that patients with this pre-existing B-cell clone in their bone marrow are most at risk for developing aggressive lymphoma,” added study author Ulrich Jäger, MD, of the Medical University of Vienna.

“We also know that up to 16% of people with myelofibrosis have immunoglobulin gene rearrangements like this B-cell clone. Therefore, our findings suggest that all patients with myelofibrosis should be tested for such gene rearrangements before prescribing JAK inhibitors to treat their disease.”

Micrograph showing myelofibrosis

New research indicates that JAK inhibitors may increase the risk of lymphoma in patients with myelofibrosis (MF).

The patients studied had a 15- to 25-fold higher risk of developing B-cell lymphoma if they received treatment with JAK inhibitors.

The researchers speculate that screening MF patients for a pre-existing B-cell clone before starting JAK inhibitor therapy may help prevent lymphoma development.

Heinz Gisslinger, MD, of the Medical University of Vienna in Austria, and his colleagues conducted this research and reported the findings in Blood.

“[W]e started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment,” Dr Gisslinger said.

Therefore, he and his colleagues assessed 626 patients receiving treatment for myeloproliferative neoplasms (MPNs) at the Medical University of Vienna.

The incidence of B-cell lymphoma was 5.8% (4/69) in patients treated with JAK inhibitors and 0.36% (2/557) in patients who did not receive JAK inhibitors. That amounts to a 16-fold increased risk of lymphoma in patients receiving JAK inhibitors.

When the researchers analyzed only patients with primary MF (n=216), the increased risk of B-cell lymphoma was even greater. The incidence of lymphoma was 9.68% (3/31) in patients treated with JAK inhibitors and 0.54% (1/185) in patients who did not receive JAK inhibitors.

That corresponds to a 19-fold increased risk of B-cell lymphoma in primary MF patients treated with JAK inhibitors. When the researchers adjusted for age, there was a 21-fold greater risk. When they adjusted for sex, the risk was 25 times higher.

In a second cohort of 929 MPN patients, the incidence of B-cell lymphoma was 3.51% (2/57) in patients who received JAK inhibitors and 0.23% (2/872) in patients who did not. This corresponds to a 15-fold increased risk of lymphoma in the JAK inhibitor recipients.

Lymphoma cases

In all, there were 6 patients who developed lymphoma after JAK inhibitor treatment. Five developed diffuse large B-cell lymphoma, and 1 had high-grade B-cell lymphoma not otherwise specified.

Four of the patients had primary MF, 1 had post-polycythemia vera MF, and 1 had post-essential thrombocythemia (ET) MF. Five patients had a JAK2V617F mutation, and 1 (the post-ET MF patient) had a CALR mutation.

All 6 patients had received treatment with ruxolitinib. One patient also received fedratinib.

B-cell clone

The researchers studied bone marrow samples from 54 of the 69 patients treated with JAK inhibitors in the first cohort. The team found a pre-existing B-cell clone in 3 of the 4 patients who developed lymphoma. Further investigation suggested this was the clone that later transformed into lymphoma.

The researchers also found an association between JAK inhibition and an increased frequency of aggressive B-cell lymphomas in mouse models.

“By replicating this link between this B-cell clone and aggressive lymphoma, we hope to speed the discovery of an alternative therapy for myelofibrosis,” said study author Veronica Sexl, MD, of the University of Veterinary Medicine in Vienna. “These findings are going to be valuable in clinical care.”

“We determined that patients with this pre-existing B-cell clone in their bone marrow are most at risk for developing aggressive lymphoma,” added study author Ulrich Jäger, MD, of the Medical University of Vienna.

“We also know that up to 16% of people with myelofibrosis have immunoglobulin gene rearrangements like this B-cell clone. Therefore, our findings suggest that all patients with myelofibrosis should be tested for such gene rearrangements before prescribing JAK inhibitors to treat their disease.”

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.  

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.  

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.  

The FP diagnosed syringomas in this patient.

He explained that the bumps are benign tumors that occur frequently on the lower eyelids and upper cheeks. They are completely unrelated to the birth control pill and can develop in men, and run in families, too. While syringomas appear to occur more often in women than men, there are no known causative agents. These are benign growths of the eccrine sweat glands.

Treatment options include cryosurgery, electrosurgery, or chemical destruction with trichloroacetic acid. All of these approaches need to be performed carefully, as the syringomas are so close to the eye. Also, these treatments are only modestly effective; new syringomas can form. And there are no preventive treatments.

In this case, the patient had light brown skin, so there was a risk of causing permanent hypopigmentation with any of these destructive methods. The patient was reassured about the benign nature of the condition; she decided not to seek therapy.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP diagnosed syringomas in this patient.

He explained that the bumps are benign tumors that occur frequently on the lower eyelids and upper cheeks. They are completely unrelated to the birth control pill and can develop in men, and run in families, too. While syringomas appear to occur more often in women than men, there are no known causative agents. These are benign growths of the eccrine sweat glands.

Treatment options include cryosurgery, electrosurgery, or chemical destruction with trichloroacetic acid. All of these approaches need to be performed carefully, as the syringomas are so close to the eye. Also, these treatments are only modestly effective; new syringomas can form. And there are no preventive treatments.

In this case, the patient had light brown skin, so there was a risk of causing permanent hypopigmentation with any of these destructive methods. The patient was reassured about the benign nature of the condition; she decided not to seek therapy.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP diagnosed syringomas in this patient.

He explained that the bumps are benign tumors that occur frequently on the lower eyelids and upper cheeks. They are completely unrelated to the birth control pill and can develop in men, and run in families, too. While syringomas appear to occur more often in women than men, there are no known causative agents. These are benign growths of the eccrine sweat glands.

Treatment options include cryosurgery, electrosurgery, or chemical destruction with trichloroacetic acid. All of these approaches need to be performed carefully, as the syringomas are so close to the eye. Also, these treatments are only modestly effective; new syringomas can form. And there are no preventive treatments.

In this case, the patient had light brown skin, so there was a risk of causing permanent hypopigmentation with any of these destructive methods. The patient was reassured about the benign nature of the condition; she decided not to seek therapy.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Epidermal nevus and nevus sebaceous. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:958-962.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.