Mixed Topics

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

The study received no outside funding. The researchers and Dr. Girgis had no financial conflicts to disclose.

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

The study received no outside funding. The researchers and Dr. Girgis had no financial conflicts to disclose.

More than half of research on homeopathic remedies is unpublished or unregistered, according to a new analysis.

Homeopathy is a form of alternative medicine based on the concept that increasing dilution of a substance leads to a stronger treatment effect.

The authors of the new paper, published in BMJ Evidence-Based Medicine, also found that a quarter of the 90 randomized published trials on homeopathic remedies they analyzed changed their results before publication.

The benefits of homeopathy touted in studies may be greatly exaggerated, suggest the authors, Gerald Gartlehner, MD, of Danube University, Krems, Austria, and colleagues.

The results raise awareness that published homeopathy trials represent a limited proportion of research, skewed toward favorable results, they wrote.

“This likely affects the validity of the body of evidence of homeopathic literature and may substantially overestimate the true treatment effect of homeopathic remedies,” they concluded.

Homeopathy as practiced today was developed approximately 200 years ago in Germany, and despite ongoing debate about its effectiveness, it remains a popular alternative to conventional medicine in many developed countries, the authors noted.

According to the National Institutes of Health, homeopathy is based on the idea of “like cures like,” meaning that a disease can be cured with a substance that produces similar symptoms in healthy people, and the “law of minimum dose,” meaning that a lower dose of medication will be more effective. “Many homeopathic products are so diluted that no molecules of the original substance remain,” according to the NIH.

Homeopathy is not subject to most regulatory requirements, so assessment of effectiveness of homeopathic remedies is limited to published data, the researchers said. “When no information is publicly available about the majority of homeopathic trials, sound conclusions about the efficacy and the risks of using homeopathic medicinal products for treating health conditions are impossible,” they wrote.
 

Study methods and findings

The researchers examined 17 trial registries for studies involving homeopathic remedies conducted since 2002.

The registries included clinicaltrials.gov, the EU Clinical Trials Register, and the International Clinical Trials Registry Platform up to April 2019 to identify registered homeopathy trials.

To determine whether registered trials were published and to identify trials that were published but unregistered, the researchers examined PubMed, the Allied and Complementary Medicine Database, Embase, and Google Scholar up to April 2021.

They found that approximately 38% of registered trials of homeopathy were never published, and 53% of the published randomized, controlled trials (RCTs) were not registered. Notably, 25% of the trials that were registered and published showed primary outcomes that were changed compared with the registry.

The number of registered homeopathy trials increased significantly over the past 5 years, but approximately one-third (30%) of trials published during the last 5 years were not registered, they said. In a meta-analysis, unregistered RCTs showed significantly greater treatment effects than registered RCTs, with standardized mean differences of –0.53 and –0.14, respectively.

The study findings were limited by several factors including the potential for missed records of studies not covered by the registries searched. Other limitations include the analysis of pooled data from homeopathic treatments that may not generalize to personalized homeopathy, and the exclusion of trials labeled as terminated or suspended.
 

Proceed with caution before recommending use of homeopathic remedies, says expert

Linda Girgis, MD, noted that prior to reading this report she had known that most homeopathic remedies didn’t have any evidence of being effective, and that, therefore, the results validated her understanding of the findings of studies of homeopathy.

The study is especially important at this time in the wake of the COVID-19 pandemic, Dr. Girgis, a family physician in private practice in South River, N.J., said in an interview.

“Many people are promoting treatments that don’t have any evidence that they are effective, and more people are turning to homeopathic treatments not knowing the risks and assuming they are safe,” she continued. “Many people are taking advantage of this and trying to cash in on this with ill-proven remedies.”

Homeopathic remedies become especially harmful when patients think they can use them instead of traditional medicine, she added.

Noting that some homeopathic remedies have been studied and show some evidence that they work, Dr. Girgis said there may be a role for certain ones in primary care.

“An example would be black cohosh or primrose oil for perimenopausal hot flashes. This could be a good alternative when you want to avoid hormonal supplements,” she said.

At the same time, Dr. Girgis advised clinicians to be cautious about suggesting homeopathic remedies to patients.

“Homeopathy seems to be a good money maker if you sell these products. However, you are not protected from liability and can be found more liable for prescribing off-label treatments or those not [Food and Drug Administration] approved,” Dr. Girgis said. Her general message to clinicians: Stick with evidence-based medicine.

Her message to patients who might want to pursue homeopathic remedies is that just because something is “homeopathic” or natural doesn’t mean that it is safe.

“There are some [homeopathic] products that have caused liver damage or other problems,” she explained. “Also, these remedies can interact with other medications.”

The study received no outside funding. The researchers and Dr. Girgis had no financial conflicts to disclose.

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

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

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

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

It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.

Now, new evidence published in Nature Communications suggests even one drink a day is linked to detectable changes in the brain, though it’s not clear whether the alcohol is causing the differences.

Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.

But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.

The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.

But could even this modest amount of alcohol make a difference to our brains?

Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.

In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.

But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.

Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.

Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.

The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.

And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.

Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.

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

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

Scientists are trying different approaches to developing vaccines against norovirus, seeking to replicate the success seen in developing shots against rotavirus.

Speaking at the 12th World Congress of the World Society for Pediatric Infectious Diseases (WSPID), Miguel O’Ryan, MD, of the University of Chile, Santiago, presented an overview of candidate vaccines. Dr. O’Ryan has been involved for many years with research on rotavirus vaccines and has branched into work with the somewhat similar norovirus.

With advances in preventing rotavirus, norovirus has emerged in recent years as a leading cause of acute gastroenteritis (AGE) in most countries worldwide. It’s associated with almost 20% of all acute diarrheal cases globally and with an estimated 685 million episodes and 212,000 deaths annually, Dr. O’Ryan and coauthors reported in a review in the journal Viruses.

If successful, norovirus vaccines may be used someday to prevent outbreaks among military personnel, as this contagious virus has the potential to disrupt missions, Dr. O’Ryan and coauthors wrote. They also said people might consider getting norovirus vaccines ahead of trips to prevent traveler’s diarrhea. But most importantly, these kinds of vaccines could reduce diarrhea-associated hospitalizations and deaths of children. 

Takeda Pharmaceutical Company, for whom Dr. O’Ryan has done consulting, last year announced a collaboration with Frazier Healthcare Partners to launch HilleVax. Based in Boston, the company is intended to commercialize Takeda’s norovirus vaccine candidate.

The Takeda-HilleVax candidate vaccine injection has advanced as far as phase 2 studies, including a test done over two winter seasons in U.S. Navy recruits. Takeda and U.S. Navy scientists reported in 2020 in the journal Vaccine that the primary efficacy outcome for this test could not be evaluated due to an unexpectedly low number of cases of norovirus. Still, data taken from this study indicate that the vaccine induces a broad immune response, the scientists reported.

In his WSPID presentation, Dr. O’Ryan also mentioned an oral norovirus vaccine candidate that the company Vaxart is developing, referring to this as a “very interesting approach.” 
 

Betting on the gut

Based in South San Francisco, California, Vaxart is pursuing a theory that a vaccine designed to generate mucosal antibodies locally in the intestine, in addition to systemic antibodies in the blood, may better protect against norovirus infection than an injectable vaccine.

“A key ability to protect against norovirus needs to come from an intestinal immune response, and injected vaccines don’t give those very well,” Sean Tucker, PhD, the founder and chief scientific officer of Vaxart, told this news organization in an interview. “We think that’s one of the reasons why our oral approaches can have significant advantages.”

Challenges to developing a norovirus vaccine have included a lack of good animal models to use in research and a lack of an ability to grow the virus well in cell culture, Dr. Tucker said.

Vaxart experienced disruptions in its research during the early stages of the pandemic but has since picked up the pace of its efforts to develop its oral vaccine, Dr. Tucker said during the interview.

In a recent filing with the Securities and Exchange Commission, Vaxart said in early 2021 it resumed its norovirus vaccine program by initiating three clinical studies. These included a phase 1b placebo-controlled dose ranging study in healthy elderly adults aged 55-80. Data from these trials may be unveiled in the coming months.

Vaxart said that this year it has already initiated a phase 2 norovirus challenge study, which will evaluate safety, immunogenicity, and clinical efficacy of a vaccine candidate against placebo.

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

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

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

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

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

The genetically altered pig’s heart “worked like a rock star, beautifully functioning,” the surgeon who performed the pioneering Jan. 7 xenotransplant procedure said in a press statement on the death of the patient, David Bennett Sr.

“He wasn’t able to overcome what turned out to be devastating – the debilitation from his previous period of heart failure, which was extreme,” said Bartley P. Griffith, MD, clinical director of the cardiac xenotransplantation program at the University of Maryland, Baltimore.

University of Maryland Medical Center

Representatives of the institution aren’t offering many details on the cause of Mr. Bennett’s death on March 8, 60 days after his operation, but said they will elaborate when their findings are formally published. But their comments seem to downplay the unique nature of the implanted heart itself as a culprit and instead implicate the patient’s diminished overall clinical condition and what grew into an ongoing battle with infections.

The 57-year-old Bennett, bedridden with end-stage heart failure, judged a poor candidate for a ventricular assist device, and on extracorporeal membrane oxygenation (ECMO), reportedly was offered the extraordinary surgery after being turned down for a conventional transplant at several major centers.

“Until day 45 or 50, he was doing very well,” Muhammad M. Mohiuddin, MD, the xenotransplantation program’s scientific director, observed in the statement. But infections soon took advantage of his hobbled immune system.

Given his “preexisting condition and how frail his body was,” Dr. Mohiuddin said, “we were having difficulty maintaining a balance between his immunosuppression and controlling his infection.” Mr. Bennett went into multiple organ failure and “I think that resulted in his passing away.”


 

Beyond wildest dreams

The surgeons confidently framed Mr. Bennett’s experience as a milestone for heart xenotransplantation. “The demonstration that it was possible, beyond the wildest dreams of most people in the field, even, at this point – that we were able to take a genetically engineered organ and watch it function flawlessly for 9 weeks – is pretty positive in terms of the potential of this therapy,” Dr. Griffith said.

But enough questions linger that others were more circumspect, even as they praised the accomplishment. “There’s no question that this is a historic event,” Mandeep R. Mehra, MD, of Harvard Medical School, and director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital, both in Boston, said in an interview.

Still, “I don’t think we should just conclude that it was the patient’s frailty or death from infection,” Dr. Mehra said. With so few details available, “I would be very careful in prematurely concluding that the problem did not reside with the heart but with the patient. We cannot be sure.”

For example, he noted, “6 to 8 weeks is right around the time when some cardiac complications, like accelerated forms of vasculopathy, could become evident.” Immune-mediated cardiac allograft vasculopathy is a common cause of heart transplant failure.

Or, “it could as easily have been the fact that immunosuppression was modified at 6 to 7 weeks in response to potential infection, which could have led to a cardiac compromise,” Dr. Mehra said. “We just don’t know.”

“It’s really important that this be reported in a scientifically accurate way, because we will all learn from this,” Lori J. West, MD, DPhil, said in an interview.

Little seems to be known for sure about the actual cause of death, “but the fact there was not hyperacute rejection is itself a big step forward. And we know, at least from the limited information we have, that it did not occur,” observed Dr. West, who directs the Alberta Transplant Institute, Edmonton, and the Canadian Donation and Transplantation Research Program. She is a professor of pediatrics with adjunct positions in the departments of surgery and microbiology/immunology.

Dr. West also sees Mr. Bennett’s struggle with infections and adjustments to his unique immunosuppressive regimen, at least as characterized by his care team, as in line with the experience of many heart transplant recipients facing the same threat.

“We already walk this tightrope with every transplant patient,” she said. Typically, they’re put on a somewhat standardized immunosuppressant regimen, “and then we modify it a bit, either increasing or decreasing it, depending on the posttransplant course.” The regimen can become especially intense in response to new signs of rejection, “and you know that that’s going to have an impact on susceptibility to all kinds of infections.”
 

Full circle

The porcine heart was protected along two fronts against assault from Mr. Bennett’s immune system and other inhospitable aspects of his physiology, either of which could also have been obstacles to success: Genetic modification (Revivicor) of the pig that provided the heart, and a singularly aggressive antirejection drug regimen for the patient.

The knockout of three genes targeting specific porcine cell-surface carbohydrates that provoke a strong human antibody response reportedly averted a hyperacute rejection response that would have caused the graft to fail almost immediately.

Other genetic manipulations, some using CRISPR technology, silenced genes encoded for porcine endogenous retroviruses. Others were aimed at controlling myocardial growth and stemming graft microangiopathy.  

Mr. Bennett himself was treated with powerful immunosuppressants, including an investigational anti-CD40 monoclonal antibody (KPL-404, Kiniksa Pharmaceuticals) that, according to UMSOM, inhibits a well-recognized pathway critical to B-cell proliferation, T-cell activation, and antibody production.

“I suspect the patient may not have had rejection, but unfortunately, that intense immunosuppression really set him up – even if he had been half that age – for a very difficult time,” David A. Baran, MD, a cardiologist from Sentara Advanced Heart Failure Center, Norfolk, Va., who studies transplant immunology, said in an interview.

“This is in some ways like the original heart transplant in 1967, when the ability to do the surgery evolved before understanding of the immunosuppression needed. Four or 5 years later, heart transplantation almost died out, before the development of better immunosuppressants like cyclosporine and later tacrolimus,” Dr. Baran said.

“The current age, when we use less immunosuppression than ever, is based on 30 years of progressive success,” he noted. This landmark xenotransplantation “basically turns back the clock to a time when the intensity of immunosuppression by definition had to be extremely high, because we really didn’t know what to expect.”
 

Emerging role of xeno-organs

Xenotransplantation has been touted as potential strategy for expanding the pool of organs available for transplantation. Mr. Bennett’s “breakthrough surgery” takes the world “one step closer to solving the organ shortage crisis,” his surgeon, Dr. Griffith, announced soon after the procedure. “There are simply not enough donor human hearts available to meet the long list of potential recipients.”

But it’s not the only proposed approach. Measures could be taken, for example, to make more efficient use of the human organs that become available, partly by opening the field to additional less-than-ideal hearts and loosening regulatory mandates for projected graft survival.

“Every year, more than two-thirds of donor organs in the United States are discarded. So it’s not actually that we don’t have enough organs, it’s that we don’t have enough organs that people are willing to take,” Dr. Baran said. Still, it’s important to pursue all promising avenues, and “the genetic manipulation pathway is remarkable.”

But “honestly, organs such as kidneys probably make the most sense” for early study of xenotransplantation from pigs, he said. “The waiting list for kidneys is also very long, but if the kidney graft were to fail, the patient wouldn’t die. It would allow us to work out the immunosuppression without putting patients’ lives at risk.”

Often overlooked in assessments of organ demand, Dr. West said, is that “a lot of patients who could benefit from a transplant will never even be listed for a transplant.” It’s not clear why; perhaps they have multiple comorbidities, live too far from a transplant center, “or they’re too big or too small. Even if there were unlimited organs, you could never meet the needs of people who could benefit from transplantation.”

So even if more available donor organs were used, she said, there would still be a gap that xenotransplantation could help fill. “I’m very much in favor of research that allows us to continue to try to find a pathway to xenotransplantation. I think it’s critically important.”

Unquestionably, “we now need to have a dialogue to entertain how a technology like this, using modern medicine with gene editing, is really going to be utilized,” Dr. Mehra said. The Bennett case “does open up the field, but it also raises caution.” There should be broad participation to move the field forward, “coordinated through either societies or nationally allocated advisory committees that oversee the movement of this technology, to the next step.”

Ideally, that next step “would be to do a safety clinical trial in the right patient,” he said. “And the right patient, by definition, would be one who does not have a life-prolonging option, either mechanical circulatory support or allograft transplantation. That would be the goal.”

Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board NuPulseCV, Leviticus, and FineHeart. Dr. Baran disclosed consulting for Getinge and LivaNova; speaking for Pfizer; and serving on trial steering committees for CareDx and Procyrion, all unrelated to xenotransplantation. Dr. West has declared no relevant conflicts.

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

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

Sleeping with a light on can play havoc with insulin levels and consequently impair the response to glucose, a 2-night sleep-lab study of 20 people indicates.

“The most important finding” is that, compared with one night in a dim light environment, “one night of exposure to a moderate level of room light while sleeping with eyes closed increased heart rate and sympathetic [nervous system] activity during the entire sleep period,” said senior author Phyllis C. Zee, MD, PhD.

And on the morning following the moderate room light condition, a higher amount of insulin secretion was required to normalize glucose levels following ingestion of a bolus of glucose in an oral glucose tolerance test, consistent with higher insulin resistance, Dr. Zee, director of the center for circadian and sleep medicine at Northwestern University, Chicago, told this news organization in an email.

The study by Ivy C. Mason, PhD, also of Northwestern University, and colleagues was published March 14 in the Proceedings of the National Academy of Sciences.

Melatonin levels were similar under the two light conditions, Dr. Zee added, which “suggests that the effect of light during sleep on these cardiometabolic measures were more likely due to activation of the sympathetic [nervous] system and less likely due to changes in sleep or suppression of melatonin by light.”

“Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health,” the researchers conclude.

That means “turn lights off before sleeping,” Dr. Zee elaborated. If a light is needed for safety reasons, keep it as dim as possible, she advises, and avoid exposure to blue or green light, but instead try red-amber colors.
 

How light during sleep may affect insulin, melatonin, heart rate

Several studies have investigated the effect of light on sleep and metabolic outcomes, the researchers explain.

In one study, light in the bedroom was associated with obesity in women, and in another study, it was associated with risk of type 2 diabetes in an elderly population.

Research has suggested that nighttime light exposure may alter glucose metabolism by increasing insulin resistance; lowering melatonin levels, which alters insulin secretion; and having an arousing effect on the sympathetic autonomic nervous system (increasing the stress hormone cortisol or heart rate, and decreasing heart rate variability).

However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period has not been fully investigated.

The researchers enrolled and randomized 20 healthy young adults who were 18-40 years old and regularly went to sleep between 9 p.m. and 1 a.m. and slept 6.5-8.5 hours, to sleep 2 nights in the sleep laboratory under two conditions.

Ten participants (eight women, two men) slept in a dim light condition on night 1 and in a moderate light condition on night 2. The other 10 participants (six women, four men) slept 2 nights in the dim light condition.

The moderate light condition consisted of four 60-watt incandescent overhead ceiling light bulbs (a total of 100 lux), which “is bright enough to see, but not to read comfortably,” Dr. Zee explained. “It’s like hallway light in an apartment. But the people were sleeping, so about 90% of the light would be blocked by the eyelids.”

The dim light condition was less than 3 lux, which is dimmer than a night light.

When participants were awake, the room lighting was 240 lux.

Participants in each group were a mean age of 27 years and had a mean body mass index of 23 and 24 kg/m².

The week before the study, participants went to bed at 11 p.m. and slept for 7 hours (based on actigraphy measures). During the laboratory stay, the participants were allowed to sleep 8 hours, during which polysomnography was performed.  

They received standard meals at 2.5, 5, and 11 hours after waking and had 30 minutes to eat them. Snacking and caffeine were not permitted.

Participants were instructed to remain seated or standing in their room, but not exercise, when they were not sleeping. Blood samples to determine melatonin levels were collected hourly during wake and sleep via an intravenous line.

Participants slept for a similar time, around 7 hours, in both conditions.

Although melatonin levels were similar in both conditions, this was a relatively small sample, the researchers caution.

In the room light condition, participants spent proportionately more time in stage N2 sleep and less in slow-wave and rapid eye movement sleep. There was no increase in sleep fragmentation or arousals.

The research was partly supported by the Center for Circadian and Sleep Medicine at Northwestern University, the National Center for Advancing Translational Sciences, the National Institutes of Health, and the American Heart Association. The researchers have reported no relevant financial relationships.

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

John Giacomini, MD, has pleaded guilty to one count of abusive sexual contact of a female physician he was supervising, the Department of Justice (DOJ) has announced.

Dr. Giacomini, 73, of Atherton, California, had practiced medicine and cardiology for more than 30 years and served as chief of the cardiology section at the VA Hospital in Palo Alto from 1985 to 2018.

According to the statement from DOJ, starting in the fall of 2017, Dr. Giacomini repeatedly subjected a subordinate doctor to unwanted and unwelcome sexual contact, which included hugging, kissing, and intimate touching while on VA premises.

The victim explicitly told Dr. Giacomini she was not interested in a romantic or sexual relationship with him and forcibly resisted his repeated attempts to kiss her, the statement notes.

The abuse continued, culminating in December 2017 with the incident of abusive sexual contact, the DOJ says.

Afterward, the victim resigned from her position at the VA, citing Dr. Giacomini’s behavior as her principal reason for leaving.

“As a federal employee for well over 30 years, [Dr.] Giacomini was trained throughout his career on the prevention of workplace sexual assault and sexual harassment,” the DOJ says.

“As a supervisor and manager, [Dr.] Giacomini had an obligation to the VA and to his subordinates to prevent workplace sexual harassment and disclose any harassing behavior of which he became aware. He failed to do this,” the DOJ says.

A federal grand jury indicted Dr. Giacomini in March 2020, charging him with one count of abusive sexual contact. Dr. Giacomini has now pleaded guilty to the charge, a felony.

Sentencing is scheduled for July 12. Dr. Giacomini faces a maximum sentence of 2 years in prison, a fine of $250,000, restitution, and supervised release.

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

John Giacomini, MD, has pleaded guilty to one count of abusive sexual contact of a female physician he was supervising, the Department of Justice (DOJ) has announced.

Dr. Giacomini, 73, of Atherton, California, had practiced medicine and cardiology for more than 30 years and served as chief of the cardiology section at the VA Hospital in Palo Alto from 1985 to 2018.

According to the statement from DOJ, starting in the fall of 2017, Dr. Giacomini repeatedly subjected a subordinate doctor to unwanted and unwelcome sexual contact, which included hugging, kissing, and intimate touching while on VA premises.

The victim explicitly told Dr. Giacomini she was not interested in a romantic or sexual relationship with him and forcibly resisted his repeated attempts to kiss her, the statement notes.

The abuse continued, culminating in December 2017 with the incident of abusive sexual contact, the DOJ says.

Afterward, the victim resigned from her position at the VA, citing Dr. Giacomini’s behavior as her principal reason for leaving.

“As a federal employee for well over 30 years, [Dr.] Giacomini was trained throughout his career on the prevention of workplace sexual assault and sexual harassment,” the DOJ says.

“As a supervisor and manager, [Dr.] Giacomini had an obligation to the VA and to his subordinates to prevent workplace sexual harassment and disclose any harassing behavior of which he became aware. He failed to do this,” the DOJ says.

A federal grand jury indicted Dr. Giacomini in March 2020, charging him with one count of abusive sexual contact. Dr. Giacomini has now pleaded guilty to the charge, a felony.

Sentencing is scheduled for July 12. Dr. Giacomini faces a maximum sentence of 2 years in prison, a fine of $250,000, restitution, and supervised release.

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

John Giacomini, MD, has pleaded guilty to one count of abusive sexual contact of a female physician he was supervising, the Department of Justice (DOJ) has announced.

Dr. Giacomini, 73, of Atherton, California, had practiced medicine and cardiology for more than 30 years and served as chief of the cardiology section at the VA Hospital in Palo Alto from 1985 to 2018.

According to the statement from DOJ, starting in the fall of 2017, Dr. Giacomini repeatedly subjected a subordinate doctor to unwanted and unwelcome sexual contact, which included hugging, kissing, and intimate touching while on VA premises.

The victim explicitly told Dr. Giacomini she was not interested in a romantic or sexual relationship with him and forcibly resisted his repeated attempts to kiss her, the statement notes.

The abuse continued, culminating in December 2017 with the incident of abusive sexual contact, the DOJ says.

Afterward, the victim resigned from her position at the VA, citing Dr. Giacomini’s behavior as her principal reason for leaving.

“As a federal employee for well over 30 years, [Dr.] Giacomini was trained throughout his career on the prevention of workplace sexual assault and sexual harassment,” the DOJ says.

“As a supervisor and manager, [Dr.] Giacomini had an obligation to the VA and to his subordinates to prevent workplace sexual harassment and disclose any harassing behavior of which he became aware. He failed to do this,” the DOJ says.

A federal grand jury indicted Dr. Giacomini in March 2020, charging him with one count of abusive sexual contact. Dr. Giacomini has now pleaded guilty to the charge, a felony.

Sentencing is scheduled for July 12. Dr. Giacomini faces a maximum sentence of 2 years in prison, a fine of $250,000, restitution, and supervised release.

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

When dermatologists are uncertain about a diagnosis, they might seek help from a book or book chapter written by Dirk M. Elston, MD, a past president of the American Academy of Dermatology and the American Society of Dermatopathology who has authored more than 600 peer-reviewed publications and 92 textbook chapters.

After earning his undergraduate degree from Pennsylvania State University and his medical degree from Jefferson Medical College in Philadelphia, Dr. Elston completed an internship and a dermatology residency at Walter Reed Army Medical Center in Washington, as well as a dermatopathology fellowship at the Cleveland Clinic. He currently is professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina in Charleston.

Dr. Elston is one of five authors of “Andrews’ Diseases of the Skin),” coauthor with Tammie Ferringer, MD, of the “Dermatopathology” textbook, and editor in chief of the Requisites in Dermatology series of textbooks. In 2018, he succeeded Bruce H. Thiers, MD, as editor of the Journal of the American Academy of Dermatology and in 2021, received the AAD’s Gold Medal Award, which is the academy’s highest honor.

In an interview, Dr. Elston reflected on his mentors, shared how he manages his many responsibilities as a clinician, teacher, and editor, and talked about the promising future of dermatology.

Who inspired you most to pursue a career in medicine? My grandmother, Annie Elston, was a physician and dedicated her life to helping others. She was a front-line medic during World War I, helped to run a neonatal syphilis ward after the war, and practiced pediatrics in New York City until her death. She was a great role model.

Did you enter medical school knowing that you wanted to become a dermatologist? If not, what was the turning point for you? I didn’t really know much about dermatology when I entered medical school. I fell in love with the specialty during a rotation.

What was the most memorable experience from your dermatology residency at Walter Reed Army Medical Center? There were so many interesting patients, including many tropical diseases.

Why did you choose to pursue a fellowship in dermatopathology? What was it about this subspeciality that piqued your interest? Great teachers, including Tim Berger, MD, George Lupton, MD, and Dean Pearson, MD. They inspired me to seek a dermpath fellowship and I was lucky enough to train with Wilma Bergfeld, MD.

In your opinion, what’s been the most important advance in dermatopathology to date?

Immunohistochemistry changed the specialty. Now molecular diagnostics is a second wave of major advancement.

How do you stay passionate about both dermatology and dermatopathology? The patients, residents, and fellows keep it interesting. It’s a two-way street. I learn as much as I teach.

You’ve had a remarkable run at the Journal of the American Academy of Dermatology, starting as deputy editor in 2008 before becoming editor in 2018. What’s been most rewarding about this role for you? It is a labor of love and such a privilege to see everyone’s best work.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint? Fear of the unknown is always a challenge with a new epidemic and worse with a pandemic. The patients still needed to be seen but it was a challenge with some buildings closed and some personnel afraid to come to work.

Is there anything you would tell your younger self in terms of career advice? Enjoy every step of the journey.

Considering your various work responsibilities as a clinician, teacher, and editor, what’s your strategy for achieving a work-life balance? A good friend of mine is fond of saying that balance is an illusion. There is only resilience. I believe the truth lies somewhere in between. Make time for family, and decide what has to get done today and what can wait until tomorrow.

What development in dermatology are you most excited about in the next 5 years? We are in a golden age of therapeutic innovations that are life changing and lifesaving for our patients. I never would have believed I would see complete cures of patients with widely metastatic melanoma. From psoriasis to eczema to malignancy, our therapeutic armamentarium is dramatically better each year. It makes the practice of medicine exciting.

When dermatologists are uncertain about a diagnosis, they might seek help from a book or book chapter written by Dirk M. Elston, MD, a past president of the American Academy of Dermatology and the American Society of Dermatopathology who has authored more than 600 peer-reviewed publications and 92 textbook chapters.

After earning his undergraduate degree from Pennsylvania State University and his medical degree from Jefferson Medical College in Philadelphia, Dr. Elston completed an internship and a dermatology residency at Walter Reed Army Medical Center in Washington, as well as a dermatopathology fellowship at the Cleveland Clinic. He currently is professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina in Charleston.

Dr. Elston is one of five authors of “Andrews’ Diseases of the Skin),” coauthor with Tammie Ferringer, MD, of the “Dermatopathology” textbook, and editor in chief of the Requisites in Dermatology series of textbooks. In 2018, he succeeded Bruce H. Thiers, MD, as editor of the Journal of the American Academy of Dermatology and in 2021, received the AAD’s Gold Medal Award, which is the academy’s highest honor.

In an interview, Dr. Elston reflected on his mentors, shared how he manages his many responsibilities as a clinician, teacher, and editor, and talked about the promising future of dermatology.

Who inspired you most to pursue a career in medicine? My grandmother, Annie Elston, was a physician and dedicated her life to helping others. She was a front-line medic during World War I, helped to run a neonatal syphilis ward after the war, and practiced pediatrics in New York City until her death. She was a great role model.

Did you enter medical school knowing that you wanted to become a dermatologist? If not, what was the turning point for you? I didn’t really know much about dermatology when I entered medical school. I fell in love with the specialty during a rotation.

What was the most memorable experience from your dermatology residency at Walter Reed Army Medical Center? There were so many interesting patients, including many tropical diseases.

Why did you choose to pursue a fellowship in dermatopathology? What was it about this subspeciality that piqued your interest? Great teachers, including Tim Berger, MD, George Lupton, MD, and Dean Pearson, MD. They inspired me to seek a dermpath fellowship and I was lucky enough to train with Wilma Bergfeld, MD.

In your opinion, what’s been the most important advance in dermatopathology to date?

Immunohistochemistry changed the specialty. Now molecular diagnostics is a second wave of major advancement.

How do you stay passionate about both dermatology and dermatopathology? The patients, residents, and fellows keep it interesting. It’s a two-way street. I learn as much as I teach.

You’ve had a remarkable run at the Journal of the American Academy of Dermatology, starting as deputy editor in 2008 before becoming editor in 2018. What’s been most rewarding about this role for you? It is a labor of love and such a privilege to see everyone’s best work.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint? Fear of the unknown is always a challenge with a new epidemic and worse with a pandemic. The patients still needed to be seen but it was a challenge with some buildings closed and some personnel afraid to come to work.

Is there anything you would tell your younger self in terms of career advice? Enjoy every step of the journey.

Considering your various work responsibilities as a clinician, teacher, and editor, what’s your strategy for achieving a work-life balance? A good friend of mine is fond of saying that balance is an illusion. There is only resilience. I believe the truth lies somewhere in between. Make time for family, and decide what has to get done today and what can wait until tomorrow.

What development in dermatology are you most excited about in the next 5 years? We are in a golden age of therapeutic innovations that are life changing and lifesaving for our patients. I never would have believed I would see complete cures of patients with widely metastatic melanoma. From psoriasis to eczema to malignancy, our therapeutic armamentarium is dramatically better each year. It makes the practice of medicine exciting.

When dermatologists are uncertain about a diagnosis, they might seek help from a book or book chapter written by Dirk M. Elston, MD, a past president of the American Academy of Dermatology and the American Society of Dermatopathology who has authored more than 600 peer-reviewed publications and 92 textbook chapters.

After earning his undergraduate degree from Pennsylvania State University and his medical degree from Jefferson Medical College in Philadelphia, Dr. Elston completed an internship and a dermatology residency at Walter Reed Army Medical Center in Washington, as well as a dermatopathology fellowship at the Cleveland Clinic. He currently is professor and chair of the department of dermatology and dermatologic surgery at the Medical University of South Carolina in Charleston.

Dr. Elston is one of five authors of “Andrews’ Diseases of the Skin),” coauthor with Tammie Ferringer, MD, of the “Dermatopathology” textbook, and editor in chief of the Requisites in Dermatology series of textbooks. In 2018, he succeeded Bruce H. Thiers, MD, as editor of the Journal of the American Academy of Dermatology and in 2021, received the AAD’s Gold Medal Award, which is the academy’s highest honor.

In an interview, Dr. Elston reflected on his mentors, shared how he manages his many responsibilities as a clinician, teacher, and editor, and talked about the promising future of dermatology.

Who inspired you most to pursue a career in medicine? My grandmother, Annie Elston, was a physician and dedicated her life to helping others. She was a front-line medic during World War I, helped to run a neonatal syphilis ward after the war, and practiced pediatrics in New York City until her death. She was a great role model.

Did you enter medical school knowing that you wanted to become a dermatologist? If not, what was the turning point for you? I didn’t really know much about dermatology when I entered medical school. I fell in love with the specialty during a rotation.

What was the most memorable experience from your dermatology residency at Walter Reed Army Medical Center? There were so many interesting patients, including many tropical diseases.

Why did you choose to pursue a fellowship in dermatopathology? What was it about this subspeciality that piqued your interest? Great teachers, including Tim Berger, MD, George Lupton, MD, and Dean Pearson, MD. They inspired me to seek a dermpath fellowship and I was lucky enough to train with Wilma Bergfeld, MD.

In your opinion, what’s been the most important advance in dermatopathology to date?

Immunohistochemistry changed the specialty. Now molecular diagnostics is a second wave of major advancement.

How do you stay passionate about both dermatology and dermatopathology? The patients, residents, and fellows keep it interesting. It’s a two-way street. I learn as much as I teach.

You’ve had a remarkable run at the Journal of the American Academy of Dermatology, starting as deputy editor in 2008 before becoming editor in 2018. What’s been most rewarding about this role for you? It is a labor of love and such a privilege to see everyone’s best work.

During the peak of the COVID-19 pandemic, what were your most significant challenges from both a clinical and a personal standpoint? Fear of the unknown is always a challenge with a new epidemic and worse with a pandemic. The patients still needed to be seen but it was a challenge with some buildings closed and some personnel afraid to come to work.

Is there anything you would tell your younger self in terms of career advice? Enjoy every step of the journey.

Considering your various work responsibilities as a clinician, teacher, and editor, what’s your strategy for achieving a work-life balance? A good friend of mine is fond of saying that balance is an illusion. There is only resilience. I believe the truth lies somewhere in between. Make time for family, and decide what has to get done today and what can wait until tomorrow.

What development in dermatology are you most excited about in the next 5 years? We are in a golden age of therapeutic innovations that are life changing and lifesaving for our patients. I never would have believed I would see complete cures of patients with widely metastatic melanoma. From psoriasis to eczema to malignancy, our therapeutic armamentarium is dramatically better each year. It makes the practice of medicine exciting.

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

Should pharmaceutical companies continue to do business in Russia, running ongoing clinical trials, starting new ones, or continuing to sell their products there?

Some argue that medicine and science must not get enmeshed in politics, staying above the fray to protect their independence and credibility. Other defenders of business-as-usual say the pharmaceutical industry deals in health and aids the vulnerable. Humanitarianism requires continued interaction with Russia.

I think both arguments fail. Pharma should follow the lead of other Western companies and suspend their involvement with Putin’s Russia.

We are fighting a war with Russia. It is a war of economic strangulation, social isolation, and pushing Russia as hard as we can to become a pariah state so that internal pressure on Putin will cause him to rethink his cruel, unjustified invasion or the Russian people to replace him. This pressure must be harsh and it must happen quickly. Why?

Having failed to rapidly defeat the Ukrainian army in the war’s first weeks, Russian commanders are now resorting to the horrible barbarism they used in previous wars in Chechnya and Syria: flattening cities, attacking civilians, killing children with massive and indiscriminate firepower.

To mention one recent horror among many, Russian shelling destroyed a maternity hospital in Mariupol. Ukraine’s president, Volodymyr Zelensky, in bemoaning the Russians for their continuing series of war crimes called on the world to act.

“Mariupol. Direct Strike of Russian troops at the maternity hospital,” he wrote in a Twitter post. “People, children are under the wreckage. Atrocity! How much longer will the world be an accomplice ignoring terror?”

The Russian government’s response: “It is not the first time we have seen pathetic outcries concerning the so-called atrocities,” said Minister of Foreign Affairs Sergei Lavrov, claiming the hospital was being used as a base by an “ultra-radical” Ukrainian battalion.

Health and its preservation are key parts of the aim of medicine and science. There is no way that medicine and science can ignore what war does to health, what attacks on hospitals do to the sick and those who serve them there, the psychological toll that intentional terrorism takes on civilians and their defenders, and what the destruction of infrastructure means for the long-term well-being of Ukrainians.

There can be no collusion with war criminals. There can be no denial of the inextricable link between medicine, science, and politics. Medicine and science are controlled by political forces; their use for good or evil is driven by political considerations, and each doctor, scientist, and scientific society must take a stand when politics corrodes the underlying aims of research and healing.

How far does noncooperation with Russia go? Very, very far. All research, both ongoing and new, must cease immediately. Whatever can be done to minimize harm to existing subjects in a short period of time ought to be done, but that is it.

Similarly, no sale of medicines or therapies ought to be occurring, be they life-saving or consumer products. Putin will see to it that such shipments go to the military or are sold on the black market for revenue, and there is nothing pharma companies can do to stop that.

The Russian people need to be pinched not only by the loss of cheeseburgers and boutique coffee but by products they use to maintain their well-being. War is cruel that way, but if you tolerate a government that is bombing and shelling a peaceful neighbor to oblivion, then pharma must ensure that efforts to make Putin and his kleptocratic goons feel the wrath of their fellow citizens.

Given the realities of nuclear Armageddon, the civilized world must fight obvious barbarity as best it can with sanctions, financial assaults, property seizures, and forgoing commerce, including important raw materials and health products. War, even in a fiscal form, is not without terrible costs; but achieving a rapid, just resolution against tyranny permits no exceptions for pharma or any other business if it is a war that must be fought.

Dr. Caplan is director of the division of medical ethics at New York University. He has consulted with Johnson & Johnson’s Panel for Compassionate Drug Use.



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

What antenatal treatment is indicated in a pregnant woman at 28 weeks’ gestation who has a hepatitis B viral load of 2 million copies/mL?

Continue to the answer...

This patient has a markedly elevated viral load and is at significantly increased risk of transmitting hepatitis B infection to her neonate even if the infant receives hepatitis B immune globulin immediately after birth and quickly begins the hepatitis B vaccine series. Daily antenatal treatment with tenofovir (300 mg daily) from 28 weeks until delivery will significantly reduce the risk of perinatal transmission.

What antenatal treatment is indicated in a pregnant woman at 28 weeks’ gestation who has a hepatitis B viral load of 2 million copies/mL?

Continue to the answer...

This patient has a markedly elevated viral load and is at significantly increased risk of transmitting hepatitis B infection to her neonate even if the infant receives hepatitis B immune globulin immediately after birth and quickly begins the hepatitis B vaccine series. Daily antenatal treatment with tenofovir (300 mg daily) from 28 weeks until delivery will significantly reduce the risk of perinatal transmission.

What antenatal treatment is indicated in a pregnant woman at 28 weeks’ gestation who has a hepatitis B viral load of 2 million copies/mL?

Continue to the answer...

This patient has a markedly elevated viral load and is at significantly increased risk of transmitting hepatitis B infection to her neonate even if the infant receives hepatitis B immune globulin immediately after birth and quickly begins the hepatitis B vaccine series. Daily antenatal treatment with tenofovir (300 mg daily) from 28 weeks until delivery will significantly reduce the risk of perinatal transmission.

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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

Heavy drinking during early adulthood may raise the risk for alcohol-related cancers, even after drinking stops or decreases in middle age, according to a new study from Australia.

Although alcohol is a known risk factor for cancer, people generally do not expect their heavy drinking in early adulthood to affect their cancer risk many years later, lead author Harindra Jayasekara, MBBS, MD, PhD, with Cancer Council Victoria and University of Melbourne, said in an interview. But in this analysis, “we found evidence consistent with early initiation and chronic progression of carcinogenesis linked to alcohol and its toxic metabolites.”

Courtesy Debora Cartagena, USCDCP

Impact on cancer risk

For men, relative to lifetime abstention, heavy drinking trajectories were associated with an increased risk for alcohol-related cancer overall.

The strongest associations were for the early decreasing heavy trajectory (hazard ratio, 1.75) and the late decreasing heavy trajectory (HR, 1.94), with the increasing heavy trajectory not far behind (HR, 1.45).

The strength of these associations did not change appreciably in analyses excluding current smokers at baseline.

Among men, the early decreasing heavy and late decreasing heavy intake trajectories were similarly associated with an increased risk for colorectal cancer (HR, 1.56 for early, and HR, 1.74 for late). The corresponding HR for the increasing heavy trajectory was 1.36.

For women, compared with lifetime abstention, the alcohol intake trajectory classified as increasing moderate (30-59 g/day) was associated with a greater risk for alcohol-related cancer overall (HR, 1.25). The strength of this association weakened slightly when current smokers were excluded.

Compared with lifetime abstention, the increasing moderate trajectory in women was similarly associated with an increased risk for breast cancer (HR, 1.30) and colorectal cancer (HR, 1.23).

The 2018 World Cancer Research Fund and American Institute for Cancer Research global cancer prevention recommendation on alcohol is to “avoid any alcohol,” study investigator Julie Bassett, PhD, MSc, with Cancer Council Victoria, said in an interview. “As much as it is important to limit alcohol intake during middle age to prevent cancer, we have shown that limiting intake during early adulthood is also important.”
 

‘Striking’ findings

Reached for comment, Timothy Brennan, MD, MPH, chief of clinical services at the Addiction Institute of Mount Sinai in New York, said it is “striking” that heavy drinking in early adulthood led to an increased risk for alcohol-related cancers, even among people who drank much less in middle age.

“We’ve known for decades that alcohol is not harmless, but this data adds to the growing body of literature regarding the significant dangers of heavy drinking during early adulthood,” said Dr. Brennan, who wasn’t involved in the study.

Dr. Brennan cautioned, however, that the authors studied alcohol-related cancers, and “there are likely many other [cancer] risk factors that were not analyzed in this dataset.”

Nevertheless, this evidence helps counter the “troubling narrative” that “it is somehow normal and safe to drink excessively in young adulthood.”

“It is most certainly not safe,” Dr. Brennan told this news organization . “We see in this study that drinking excessively in young adulthood can raise the risk of cancer much later in life.”

The study had no commercial funding. Dr. Bassett, Dr. Jayasekara, and Dr. Brennan have disclosed no relevant financial relationships.

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