Tennessee’s Board of Medical Examiners unanimously adopted in September 2021 a statement that said doctors spreading COVID misinformation – such as suggesting that vaccines contain microchips – could jeopardize their license to practice.

“I’m very glad that we’re taking this step,” Dr. Stephen Loyd, MD, the panel’s vice president, said at the time. “If you’re spreading this willful misinformation, for me it’s going to be really hard to do anything other than put you on probation or take your license for a year. There has to be a message sent for this. It’s not okay.”

The board’s statement was posted on a government website.

But before any physicians could be reprimanded for spreading falsehoods about COVID-19 vaccines or treatments, Republican lawmakers threatened to disband the medical board.

The growing tension in Tennessee between conservative lawmakers and the state’s medical board may be the most prominent example in the country. But the Federation of State Medical Boards, which created the language adopted by at least 15 state boards, is tracking legislation introduced by Republicans in at least 14 states that would restrict a medical board’s authority to discipline doctors for their advice on COVID.

Humayun Chaudhry, DO, the federation’s CEO, called it “an unwelcome trend.” The nonprofit association, based in Euless, Tex., said the statement is merely a COVID-specific restatement of an existing rule: that doctors who engage in behavior that puts patients at risk could face disciplinary action.

Although doctors have leeway to decide which treatments to provide, the medical boards that oversee them have broad authority over licensing. Often, doctors are investigated for violating guidelines on prescribing high-powered drugs. But physicians are sometimes punished for other “unprofessional conduct.” In 2013, Tennessee’s board fined U.S. Rep. Scott DesJarlais for separately having sexual relations with two female patients more than a decade earlier.

Still, stopping doctors from sharing unsound medical advice has proved challenging. Even defining misinformation has been difficult. And during the pandemic, resistance from some state legislatures is complicating the effort.

A relatively small group of physicians peddle COVID misinformation, but many of them associate with America’s Frontline Doctors. Its founder, Simone Gold, MD, has claimed patients are dying from COVID treatments, not the virus itself. Sherri Tenpenny, DO, said in a legislative hearing in Ohio that the COVID vaccine could magnetize patients. Stella Immanuel, MD, has pushed hydroxychloroquine as a COVID cure in Texas, although clinical trials showed that it had no benefit. None of them agreed to requests for comment.

The Texas Medical Board fined Dr. Immanuel $500 for not informing a patient of the risks associated with using hydroxychloroquine as an off-label COVID treatment.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation. This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN.

Tennessee’s Board of Medical Examiners unanimously adopted in September 2021 a statement that said doctors spreading COVID misinformation – such as suggesting that vaccines contain microchips – could jeopardize their license to practice.

“I’m very glad that we’re taking this step,” Dr. Stephen Loyd, MD, the panel’s vice president, said at the time. “If you’re spreading this willful misinformation, for me it’s going to be really hard to do anything other than put you on probation or take your license for a year. There has to be a message sent for this. It’s not okay.”

The board’s statement was posted on a government website.

But before any physicians could be reprimanded for spreading falsehoods about COVID-19 vaccines or treatments, Republican lawmakers threatened to disband the medical board.

The growing tension in Tennessee between conservative lawmakers and the state’s medical board may be the most prominent example in the country. But the Federation of State Medical Boards, which created the language adopted by at least 15 state boards, is tracking legislation introduced by Republicans in at least 14 states that would restrict a medical board’s authority to discipline doctors for their advice on COVID.

Humayun Chaudhry, DO, the federation’s CEO, called it “an unwelcome trend.” The nonprofit association, based in Euless, Tex., said the statement is merely a COVID-specific restatement of an existing rule: that doctors who engage in behavior that puts patients at risk could face disciplinary action.

Although doctors have leeway to decide which treatments to provide, the medical boards that oversee them have broad authority over licensing. Often, doctors are investigated for violating guidelines on prescribing high-powered drugs. But physicians are sometimes punished for other “unprofessional conduct.” In 2013, Tennessee’s board fined U.S. Rep. Scott DesJarlais for separately having sexual relations with two female patients more than a decade earlier.

Still, stopping doctors from sharing unsound medical advice has proved challenging. Even defining misinformation has been difficult. And during the pandemic, resistance from some state legislatures is complicating the effort.

A relatively small group of physicians peddle COVID misinformation, but many of them associate with America’s Frontline Doctors. Its founder, Simone Gold, MD, has claimed patients are dying from COVID treatments, not the virus itself. Sherri Tenpenny, DO, said in a legislative hearing in Ohio that the COVID vaccine could magnetize patients. Stella Immanuel, MD, has pushed hydroxychloroquine as a COVID cure in Texas, although clinical trials showed that it had no benefit. None of them agreed to requests for comment.

The Texas Medical Board fined Dr. Immanuel $500 for not informing a patient of the risks associated with using hydroxychloroquine as an off-label COVID treatment.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation. This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN.

Tennessee’s Board of Medical Examiners unanimously adopted in September 2021 a statement that said doctors spreading COVID misinformation – such as suggesting that vaccines contain microchips – could jeopardize their license to practice.

“I’m very glad that we’re taking this step,” Dr. Stephen Loyd, MD, the panel’s vice president, said at the time. “If you’re spreading this willful misinformation, for me it’s going to be really hard to do anything other than put you on probation or take your license for a year. There has to be a message sent for this. It’s not okay.”

The board’s statement was posted on a government website.

But before any physicians could be reprimanded for spreading falsehoods about COVID-19 vaccines or treatments, Republican lawmakers threatened to disband the medical board.

The growing tension in Tennessee between conservative lawmakers and the state’s medical board may be the most prominent example in the country. But the Federation of State Medical Boards, which created the language adopted by at least 15 state boards, is tracking legislation introduced by Republicans in at least 14 states that would restrict a medical board’s authority to discipline doctors for their advice on COVID.

Humayun Chaudhry, DO, the federation’s CEO, called it “an unwelcome trend.” The nonprofit association, based in Euless, Tex., said the statement is merely a COVID-specific restatement of an existing rule: that doctors who engage in behavior that puts patients at risk could face disciplinary action.

Although doctors have leeway to decide which treatments to provide, the medical boards that oversee them have broad authority over licensing. Often, doctors are investigated for violating guidelines on prescribing high-powered drugs. But physicians are sometimes punished for other “unprofessional conduct.” In 2013, Tennessee’s board fined U.S. Rep. Scott DesJarlais for separately having sexual relations with two female patients more than a decade earlier.

Still, stopping doctors from sharing unsound medical advice has proved challenging. Even defining misinformation has been difficult. And during the pandemic, resistance from some state legislatures is complicating the effort.

A relatively small group of physicians peddle COVID misinformation, but many of them associate with America’s Frontline Doctors. Its founder, Simone Gold, MD, has claimed patients are dying from COVID treatments, not the virus itself. Sherri Tenpenny, DO, said in a legislative hearing in Ohio that the COVID vaccine could magnetize patients. Stella Immanuel, MD, has pushed hydroxychloroquine as a COVID cure in Texas, although clinical trials showed that it had no benefit. None of them agreed to requests for comment.

The Texas Medical Board fined Dr. Immanuel $500 for not informing a patient of the risks associated with using hydroxychloroquine as an off-label COVID treatment.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation. This story is part of a partnership that includes Nashville Public Radio, NPR, and KHN.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

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

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

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

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

Hours after their births, 34 infants began a three-drug combination HIV treatment. Now, 2 years later, a third of those toddlers have tested negative for HIV antibodies and have no detectable HIV DNA in their blood. The children aren’t cured of HIV, but as many as 16 of them may be candidates to stop treatment and see if they are in fact in HIV remission.

If one or more are, it would be the first time since the Mississippi baby in 2013 that scientists have induced childhood HIV remission by beginning HIV treatment very early.    

At the Conference on Retroviruses and Opportunistic Infections, Deborah Persaud, MD, interim director of pediatric infectious diseases and professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, Md., told this news organization that the evidence suggests that more U.S. clinicians should start infants at high risk for HIV on presumptive treatment – not only to potentially prevent transmission but also to set the child up for the lowest possible viral reservoir, the first step to HIV remission.

The three-drug preemptive treatment is “not uniformly practiced,” Dr. Persaud said in an interview. “We’re at a point now where we don’t have to wait to see if we have remission” to act on these findings, she said. “The question is, should this now become standard of care for in-utero infected infants?” 

Every year, about 150 infants are born with HIV in the United States, according to the Elizabeth Glaser Pediatric AIDS Foundation. Current U.S. perinatal treatment guidelines already suggest either treatment with one or more HIV drugs at birth to attempt preventing transmission or initiating three-drug regimens for infants at high risk for perinatally acquired HIV. In this case “high risk” is defined as infants born to:

• people who haven’t received any HIV treatment before delivery or during delivery,
• people who did receive treatment but failed to achieve undetectable viral loads, or
• people who acquire HIV during pregnancy, or who otherwise weren’t diagnosed until after birth.

Trying to replicate the Mississippi baby

The Mississippi baby did eventually relapse. But ever since Dr. Persaud reported the case of that 2-year-old who went into treatment-free remission in 2013, she has been trying to figure out how to duplicate that initial success. There were several factors in that remission, but one piece researchers could control was starting treatment very early – before HIV blood tests even come back positive. So, in this trial, researchers enrolled 440 infants in Africa and Asia at high risk for in utero HIV transmission.

All 440 of those infants received their first doses of the three-drug preemptive treatment within 24 hours of birth. Of those 440 infants, 34 tested positive for HIV and remained in the trial.*

Meanwhile, in North America, South America, and African countries, another 20 infants enrolled in the trial – not as part of the protocol but because their clinicians had been influenced by the news of the Mississippi baby, Dr. Persaud said, and decided on their own to start high-risk infants on three-drug regimens preemptively.

“We wanted to take advantage of those real-world situations of infants being treated outside the clinical trials,” Dr. Persaud said.

Now there were 54 infants trying this very early treatment. In Cohort One, they started their first drug cocktail 7 hours after delivery. In Cohort Two, their first antiretroviral combination treatment was at 32.8 hours of life, and they enrolled in the trial at 8 days. Then researchers followed the infants closely, adding on lopinavir and ritonavir when age-appropriate.
 

Meeting milestones

To continue in the trial and be considered for treatment interruption, infants had to meet certain milestones. At 24 weeks, HIV RNA needed to be below 200 copies per milliliter. Then their HIV RNA needed to stay below 200 copies consistently until week 48. At week 48, they had to have an HIV RNA that was even lower – below 20 or 40 copies – with “target not detected” in the test in HIV RNA. That’s a sign that there weren’t even any trace levels of viral nucleic acid RNA in the blood to indicate HIV. Then, from week 48 on, they had to maintain that level of viral suppression until age 2.

At that point, not only did they need to maintain that level of viral suppression, they also needed to have a negative HIV antibody test and a PCR test for total HIV DNA, which had to be undetectable down to the limit of 4 copies per 106 – that is, there were fewer than 4 copies of the virus out of 1 million cells tested. Only then would they be considered for treatment interruption.

“After week 28 there was no leeway,” Dr. Persaud said. Then “they had to have nothing detectable from the first year of age. We thought the best shot at remission were cases that achieved very good and strict virologic control.”

 

Criteria for consideration

Of the 34 infants in Cohort One, 24 infants made it past the first hurdle at 24 weeks and 6 had PCR tests that found no cell-associated HIV DNA. In Cohort Two, 15 made it past the week-24 hurdle and 4 had no detectable HIV DNA via PCR test.

Now, more than 2 years out from study initiation, Dr. Persaud and colleagues are evaluating each child to see if any still meet the requirements for treatment interruption. The COVID-19 pandemic has delayed their evaluations, and it’s possible that fewer children now meet the requirements. But Dr. Persaud said there are still candidates left. An analysis suggests that up to 30% of the children, or 16, were candidates at 2 years.

“We have kids who are eligible for [antiretroviral therapy] cessation years out from this, which I think is really important,” she said in an interview. “It’s not game over.”

And although 30% is not an overwhelming victory, Dr. Persaud said the team’s goal was “to identify an N of 1 to replicate the Mississippi baby.” The study team, led by Ellen Chadwick, MD, of Northwestern University’s Feinberg School of Medicine, Chicago, and a member of the board that creates HIV perinatal treatment guidelines, is starting a new trial, using more modern, integrase inhibitor-based, three-drug regimens for infants and pairing them with broadly neutralizing antibodies. The combination used in this trial included zidovudine, or AZT.

If one of the children is able to go off treatment, it would be the first step toward creating a functional cure for HIV, starting with the youngest people affected by the virus.  

“This trial convinces me that very early treatment was the key strategy that led to remission in the Mississippi baby,” Dr. Persaud said in an interview. “We’re confirming here that the first step toward remission and cure is reducing reservoirs. We’ve got that here. Whether we need more on top of that – therapeutic vaccines, immunotherapies, or a better regimen to start out with – needs to be determined.”

The presentation was met with excitement and questions. For instance, if very early treatment works, why does it work for just 30% of the children?

Were some of the children able to control HIV on their own because they were rare post-treatment controllers? And was 30% really a victory? Others were convinced of it.

“Amazing outcome to have 30% so well suppressed after 2 years with CA-DNA not detected,” commented Hermione Lyall, MBChB, a pediatric infectious disease doctor at Imperial College Healthcare NHS Trust in the United Kingdom, in the virtual chat.

As for whether the study should change practice, Elaine Abrams, MD, professor of epidemiology and pediatrics at Columbia University Medical Center, New York, and CROI cochair, said that this study proves that the three-drug regimen is at the very least safe to start immediately.

Whether it should become standard of care everywhere is still up for discussion, she told this news organization.

“It very much depends on what you’re trying to achieve,” she said. “Postnatal prophylaxis is provided to reduce the risk of acquiring infection. That’s a different objective than early treatment. If you have 1,000 high-risk babies, how many are likely to turn out to have HIV infection? And how many of those will you be treating with three drugs and actually making this impact by doing so? And how many babies are going to be getting possibly extra treatment that they don’t need?”

Regardless, what’s clear is that treatment is essential – for mother and infant, said Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases. It needs to start, he said, by making sure all mothers know their HIV status and have access early in pregnancy to the treatment that can prevent transmission.

“So much of what’s wrong in the world is about implementation of health care,” he said in an interview. Still, “if you could demonstrate that early treatment to the mother plus early treatment to the babies [is efficacious], we could really talk about an HIV-free generation of kids.”

The study was funded by the National Institutes of Health. Dr. Persaud, Dr. Dieffenbach, Dr. Abrams, and Dr. Lyall all report no relevant financial relationships.

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

Correction, 2/16/22: An earlier version of this article misstated the number that tested positive for HIV and remained in the trial.

This article was updated 2/16/22.

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Medicinal and recreational marijuana use has become common across the country, warranting greater awareness among clinicians about any potential adverse effects of marijuana on brain health, a new American Heart Association scientific statement concludes.

The existing evidence base of preclinical and clinical research suggests that marijuana use may have a harmful effect on the brain, although the specific adverse effects have not been well defined, the statement authors said.

Smithore

Fernando D. Testai, MD, PhD, professor of neurology and rehabilitation at the University of Illinois at Chicago, led the writing panel for the statement, published online Feb. 10, 2022, in Stroke.

Numerous research studies challenge the idea that marijuana use is harmless, and instead demonstrate that cannabis, especially tetrahydrocannabinol (THC), has adverse effects on brain health, Dr. Testai and colleagues noted.

“Social media tends to overemphasize the beneficial effects of marijuana. However, its ultimate effect on brain health is still to be established. Physicians should provide periodic and unbiased education to their patients about the known and unknown ramifications of consuming cannabinoids,” Dr. Testai said.

Findings collected from animal studies demonstrate that THC interferes with normal development of signaling pathways and hinders synaptic plasticity. The authors also pointed out that these studies show connections between neurons are affected in the short term, whereas in the long haul, this contributes to changes in how neuronal networks work.

“Personally, the most striking point is the epidemiological data that indicate that the use of marijuana is widespread in the general population, and this starts early in life, particularly during adolescence,” Dr. Testai told this news organization.

Dr. Testai also noted that pregnant women are using cannabis for nausea and vomiting. Other data on prenatal exposure to cannabis show that THC hinders the signaling mechanism of the endocannabinoid system during development and ontogenesis, which ultimately leads to abnormal neurotransmission.

“Prenatal THC affects neuroanatomic areas associated with cognition and emotional regulation, including the prefrontal cortex, limbic system, and ventral tegmentum of the midbrain,” the researchers added.

The writing panel also found that marijuana use had effects on human cognition:
 

• Acute marijuana use affects impulsivity, memory, and behavioral disinhibition, they noted, that “can affect performance in real-world activities,” such as driving. The long-term effects of cannabis on cognition are “less well established.”
• Neuroimaging research has highlighted structural changes in the brain, but these data are inconsistent.
• Functional MRI studies show cannabis users may experience functional changes in regions of the brain that play a role in cognition, particularly with prolonged use.

The statement also addresses studies assessing the effects of marijuana use on cerebrovascular risk and disease, which show:

• A relation between cannabis use and increased risk for stroke.
• Frequency and other trends of cannabis use may raise stroke risk.
• Cannabis users often smoke cigarettes, which is an important factor in the association between cannabis use and stroke risk.

Looking ahead, public health initiatives are needed to increase awareness among the public about the negative effects of marijuana use. Other efforts may include setting standards regarding the concentrations of biologically active ingredients and warning notices on available formulations, the group concluded.

The document was prepared on behalf of the AHA Stroke Brain Health Science Subcommittee of the Stroke Council; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Cardiovascular and Stroke Nursing; Council on Lifestyle and Cardiometabolic Health; and Council on Peripheral Vascular Disease.

The American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists,” the document notes.

Dr. Testai reported no relevant financial relationships.

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

Recent columns on closing, selling, or merging a practice have sparked numerous questions about proper practice valuation.

Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.

Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:

• Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
• Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
• Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.

Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.

Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.

It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.

Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.

Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.

Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.

Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Recent columns on closing, selling, or merging a practice have sparked numerous questions about proper practice valuation.

Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.

Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:

• Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
• Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
• Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.

Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.

Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.

It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.

Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.

Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.

Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.

Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Recent columns on closing, selling, or merging a practice have sparked numerous questions about proper practice valuation.

Too often, physicians are not receiving a fair return on the equity they have worked so hard to build over several decades, either because they have waited too long and must accept what is offered, or because they simply take the buyer’s word for their practice’s value. Don’t put yourself in either of those positions, and don’t entertain any offers until you obtain an objective appraisal from a neutral party.

Of course, a medical practice is trickier to value than an ordinary business, and usually requires the services of an experienced professional appraiser. Entire books have been written about the process, so I can’t hope to cover it completely in 750 words; but three basic yardsticks are essential for determining the equity, or book value, of a practice:

• Tangible assets. Equipment, cash, accounts receivable, and other property owned by the practice.
• Liabilities. Accounts payable, outstanding loans, and anything else owed to others.
• Intangible assets. Sometimes called “good will” – the reputation of the physicians, the location and name recognition of the practice, the loyalty and volume of patients, and other, well, intangibles.

Valuing tangible assets is comparatively straightforward, but there are several ways to do it, and when reviewing a practice appraisal you should ask which of them was used. Depreciated value is the book value of equipment and supplies as determined by their purchase price, less the amount their value has decreased since purchase. Remaining useful life value estimates how long the equipment can be expected to last. Market (or replacement) value is the amount it would cost on the open market to replace all equipment and supplies.

Intangible assets are more difficult to value. Many components are analyzed, including location, interior and exterior decor, accessibility to patients, age and functional status of equipment, systems in place to promote efficiency, reasons why patients come back (if in fact they do), and the overall reputation of the practice in the community. Other important factors include the “payer mix” (what percentage pays cash, how many third-party contracts are in place and how well they pay, etcetera), the extent and strength of the referral base, and the presence of supplemental income streams, such as clinical research.

It is also important to determine to what extent intangible assets are transferable. For example, unique skills with a laser, neurotoxins, or filler substances, or extraordinary personal charisma, may increase your practice’s value to you, but they are worthless to the next owner, and he or she will be unwilling to pay for them unless your services become part of the deal.

Once again there are many ways to estimate intangible asset value, and once again you should ask which were used. Cash flow analysis works on the assumption that cash flow is a measure of intangible value. Capitalization of earnings puts a value, or capitalization, on the practice’s income streams using a variety of assumptions. Guideline comparison uses various databases to compare your practice with other, similar ones that have changed hands in the past.

Two newer techniques that some consider a better estimate of intangible assets are the replacement method, which estimates the costs of starting the practice over again in the current market; and the excess earnings method, which measures how far above average your practice’s earnings (and thus its overall value) are.

Asset-based valuation is the most popular, but by no means the only method available. Income-based valuation looks at the source and strength of a practice’s income stream as a creator of value, as well as whether or not its income stream under a different owner would mirror its present one. This in turn becomes the basis for an understanding of the fair market value of both tangible and intangible assets. Market valuation combines the asset-based and income-based approaches, along with an analysis of sales and mergers of comparable practices in the community, to determine the value of a practice in its local market.

Whatever methods are used, it is important that the appraisal be done by an experienced and independent financial consultant, that all techniques used in the valuation be divulged and explained, and that documentation is supplied to support the conclusions reached. This is especially important if the appraisal will be relied upon in the sale or merger of the practice.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.

Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both. 

Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever. 

As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.

Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.

Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:

•    Thromboembolism (both venous and arterial)
•    Metabolic bone diseases
•    Osteonecrosis
•    Cholelithiasis
•    Nephrolithiasis. 

Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype. 

According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:

•    Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
•    C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
•    Comprehensive metabolic panel
•    Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
•    Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)

Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.

Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification. 

In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease. 

In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.

Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both. 

Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever. 

As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.

Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.

Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:

•    Thromboembolism (both venous and arterial)
•    Metabolic bone diseases
•    Osteonecrosis
•    Cholelithiasis
•    Nephrolithiasis. 

Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype. 

According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:

•    Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
•    C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
•    Comprehensive metabolic panel
•    Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
•    Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)

Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.

Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification. 

In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease. 

In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

This patient's clinical presentation and laboratory findings are consistent with a diagnosis of Crohn disease.

Crohn disease is a chronic inflammatory bowel disease that is becoming increasingly prevalent worldwide. It is estimated to affect three to 20 persons per 100,000. When not effectively managed, Crohn disease is associated with substantial morbidity and significant impairments in lifestyle and daily activities during flares and remissions. It is characterized by a transmural granulomatous inflammation that can affect any part of the gastrointestinal tract — usually, the ileum, colon, or both. 

Abdominal pain, diarrhea, weight loss, and fatigue are often prominent symptoms in patients with Crohn disease. Crampy or steady right lower quadrant or periumbilical pain may develop; the pain both precedes and may be partially relieved by defecation. Diarrhea is frequently intermittent and is not usually grossly bloody. Diffuse abdominal pain accompanied by mucus, blood, and pus in the stool may be reported by patients if the colon is involved. Involvement of the small intestine usually presents with evidence of malabsorption, including diarrhea, abdominal pain, weight loss, and anorexia, which may be subtle early in the disease course. Anorexia, nausea, and vomiting are more common in patients with gastroduodenal involvement, whereas debilitating perirectal pain, malodorous discharge from a fistula, and disfiguring scars from active disease or previous surgery may be present in patients with perianal disease. Patients may also present with symptoms suggestive of intestinal obstruction, or with anemia, recurrent fistulas, or fever. 

As stated in guidelines from the American Gastroenterological Association (AGA), multiple streams of information, including history and physical examination, laboratory tests, endoscopy results, pathology findings, and radiographic tests, must be incorporated to arrive at a clinical diagnosis of Crohn disease. In most cases, the presence of chronic intestinal inflammation solidifies a diagnosis of Crohn disease. However, it can be challenging to differentiate Crohn disease from ulcerative colitis, particularly when the inflammation is confined to the colon. Bleeding is much more common in ulcerative colitis than in Crohn disease, whereas intestinal obstruction is common in Crohn disease and uncommon in ulcerative colitis. Fistulae and perianal disease are common in Crohn disease but are absent or rare in ulcerative colitis. Moreover, weight loss is typical in patients with Crohn disease but is uncommon in ulcerative colitis.

Additional diagnostic clues for Crohn disease include discontinuous involvement with skip areas; sparing of the rectum; deep, linear, or serpiginous ulcers of the colon; strictures; fistulas; or granulomatous inflammation. Only a small percentage of patients have granulomas on biopsy. The presence of ileitis in a patient with extensive colitis (ie, backwash ileitis) can also make determining the inflammatory bowel disease subtype challenging.

Arthropathy (both axial and peripheral) is a classic extraintestinal manifestation of Crohn disease, as are dermatologic manifestations (including pyoderma gangrenosum and erythema nodosum); ocular manifestations (including uveitis, scleritis, and episcleritis); and hepatobiliary disease (ie, primary sclerosing cholangitis). Less common extraintestinal complications of Crohn disease include:

•    Thromboembolism (both venous and arterial)
•    Metabolic bone diseases
•    Osteonecrosis
•    Cholelithiasis
•    Nephrolithiasis. 

Only 20%-30% of patients with Crohn disease will have a nonprogressive or indolent course. Clinical features that are associated with a high risk for progressive disease burden include young age at diagnosis, initial extensive bowel involvement, ileal or ileocolonic involvement, perianal or severe rectal disease, and a penetrating or stenosis disease phenotype. 

According to the AGA's Clinical Care Pathway for Crohn Disease, clinical laboratory testing in a patient with symptoms of Crohn disease should include:

•    Complete blood cell count (anemia and leukocytosis are the most common abnormalities seen)
•    C-reactive protein (not a specific marker, but may correlate with disease activity in a subset of patients)
•    Comprehensive metabolic panel
•    Fecal calprotectin (may correlate with intestinal inflammation; can help distinguish inflammatory bowel disorders from irritable bowel syndrome)
•    Erythrocyte sedimentation rate (may be elevated in some patients; not a specific marker)

Ileocolonoscopy with biopsies should be performed in the evaluation of patients with suspected Crohn disease, and disease distribution and severity should be documented at the time of diagnosis. Biopsies of uninvolved mucosa are recommended to identify the extent of histologic disease.

Consult the AGA guidelines for more extensive details on the workup for Crohn disease, including indications for additional imaging and phenotypic classification. 

In recent years, outcomes in Crohn disease have improved, which is probably the result of earlier diagnosis, increasing use of biologics, escalation or alteration of therapy based on disease severity, and endoscopic management of colorectal cancer. As noted above, Crohn disease includes multiple phenotypes, characterized by the Montreal Classification as stricturing, penetrating, inflammatory (nonstricturing and nonpenetrating), and perianal disease. Each of these phenotypes can present with a range in severity from mild to severe disease. 

In general, therapeutic recommendations for patients are based on disease location, disease severity, disease-associated complications, and future disease prognosis and are individualized according to the symptomatic response and tolerance. Current therapeutic approaches should be considered a sequential continuum to treat acute disease or induce clinical remission, then maintain response or remission. Pharmacologic options include antidiarrheal agents, anti-inflammatory therapies (eg, sulfasalazine, mesalamine), corticosteroids (a short course for severe disease), biologic therapies (eg, infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, ustekinumab), and occasionally immunosuppressive agents (tacrolimus, mycophenolate mofetil). In addition to their 2014 guidelines on the management of Crohn disease in adults, the AGA recently released guidelines specific to the medical management of moderate to severe luminal and fistulizing Crohn disease.

Bhupinder S. Anand, MD, Professor, Department of Medicine, Baylor College of Medicine, Houston, TX

Bhupinder S. Anand, MD, has disclosed no relevant financial relationships

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

At the center of the emerging science on the unintended consequences of daily long-term use of marijuana lies a paradox.

For years, medical marijuana has been used to ease nausea from cancer chemotherapy and GI conditions. Now, with greater legalization comes growing awareness that chronic use of marijuana – also known as cannabis – can trigger a condition where, ironically, a person has hard-to-control vomiting and nausea.

Doug Menuez/thinkstock

Some people with the disorder, known as “cannabinoid hyperemesis syndrome,” also report crippling belly pain.

Linda can relate. The 33-year-old Oregon resident, who asked to remain anonymous to protect her privacy, refers to a medieval spiky metal ball on a chain when describing the pain.

“Picture a mace inside your stomach, pushing up inside your chest and, at the same time, exploding out,” she said.

To seek relief, she gets down on her knees, adopts a child’s yoga pose, and runs hot water in the bathroom for hours on end, a trick many with the disorder says has provided relief. She also occasionally goes outside and tries walking it off.

“I would just wander around my neighborhood, a lot of times at like 4 or 5 in the morning,” she said. “The fresh air helps a little bit. I just keep walking down the street, take about 10 steps, stop, vomit – walk a little bit more, stop, vomit.”

Her first experience with the disorder began in the middle of one night in 2017 while she was at a conference in Las Vegas.

“We went out to eat the night before, and I woke up about 4 in the morning with just the most intense pain I’ve ever had,” she said. “I found myself in a really hot shower in between throwing up everything and trying to say get some water down. I was sharing an Airbnb with my colleagues, so it was less than ideal.”

Many people with cannabinoid hyperemesis syndrome find relief from hot baths or showers. Researchers believe that hot water helps because temperature sensors in the skin send signals to the brain that can help ease the symptoms, at least for a while.

The problem is that people with this syndrome “can’t live in the water,” said emergency doctor and medical cannabis expert Leigh Vinocur, MD.

Fast-forward 6 months to another event in Boulder, Colo. Again, Linda woke up and could not stop vomiting.

“I was not feeling any better. Showering wasn’t helping. I ended up in the hospital,” she said.

She received opioids for her pain. But neither she nor the ED staff were quite sure what was happening. Her discharge paperwork read “cannabis allergy.”

Cannabinoid hyperemesis syndrome “shatters that image of cannabis only being a good thing. It’s a bold statement, but, you know, once you start to think about it, it’s like a little too much of anything isn’t good,” Linda said.

Experts suggest greater awareness is needed to identify this syndrome earlier, by both cannabinoid users and doctors. The bouts of vomiting, in particular, can get so severe that people can end up hospitalized with dehydration, electrolyte disorders, and weight loss.

The severe electrolyte imbalances “can really be life-threatening,” said David Johnson, MD, a professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk.

“By the time they come into emergency care, they’re in bad shape,” Dr. Vinocur agreed. “Many try to ignore it, but they continue to vomit.”
 

Genetic risk factors?

One mystery is why some regular marijuana users get this syndrome while others do not.

“I can say that not everybody gets this, thank goodness,” said Ethan Russo, MD. “But there has to be a reason that certain people are susceptible and others are not.”

Interestingly, a new study from Dr. Russo and colleagues suggests that genes play a role. They identified five genetic changes that could make a chronic marijuana user more likely to have cannabinoid hyperemesis syndrome in a study published July 5, 2021, in the journal Cannabis and Cannabinoid Research.

They compared 28 people with the disorder with 12 other high-frequency marijuana users without these symptoms.

The results are not final but could help guide future research, Dr. Russo said.

“What we’ve discovered – and it was far more than we expected – is that there’s a lot more to this than a hypersensitivity to cannabis,” said Dr. Russo, a neurologist and founder/CEO of CReDO Science, a firm that promotes cannabis research and develops commercial products.

Also, he said, those affected by cannabinoid hyperemesis syndrome could be at higher risk for other conditions, such as addiction to alcohol or other substances, dementia, diabetes, and heart disease.

“Most people with [cannabinoid hyperemesis syndrome] are going to be younger,” he said. “What we’ve demonstrated is there is a risk for more serious problems for decades to come. So someone who has these symptoms really deserves a look at this genetic screening.”
 

Battling disbelief

Getting back to the paradox, many users don’t believe marijuana can trigger serious vomiting and nausea because of its reputation for doing the opposite.

“Folks that have this are just uniquely resistant to the concept that cannabis is actually the problem and not the solution,” Dr. Russo said.

“It’s kind of counterintuitive because people think: ‘Oh, cannabis helps with nausea,’ so they use more of it,” said Dr. Vinocur, who is also a spokesperson for the American College of Emergency Physicians and runs a medical cannabis practice.

Most kinds of marijuana act in this way – doing opposite things at different doses. Once a certain threshold is passed, people with cannabinoid hyperemesis syndrome are “just uniquely susceptible and really can’t tolerate any significant amount of THC,” Dr. Russo said, referring to tetrahydrocannabinol, the substance that gets marijuana users high.

Once diagnosed, quitting is the most effective strategy. But it can be tough to persuade someone to stop using marijuana.

“You do have to try and convince them ... to try abstinence and to watch and see what happens,” Dr. Vinocur said.

People should “realize the root cause of this is its cannabinoid ingestion, and the treatment is really best directed at absolute avoidance,” Dr. Johnson said.

Unfortunately, evidence also shows that once a person stops using marijuana and gets relief, going back to marijuana or other forms of cannabinoids can cause the syndrome to start all over again.

“We’ve had people that quit for a month, a year, 2 years and upon resumption, almost invariably, they’re back into bouts of the hyperemesis along with all the other [symptoms],” Dr. Russo said.

Marijuana and cannabinoids can cause digestive problems, Dr. Johnson said, which may cause more problems.
 

What recent research reveals

Cannabinoid hyperemesis syndrome is a relatively young disorder – first described in 2004 – and early reports and case studies are giving way now to studies looking into potential treatments.

So far, the strongest evidence suggests a role for an over-the-counter cream called capsaicin to help manage symptoms, but more studies are needed.

Similar to hot showers, this ingredient from chili peppers can warm the skin and trigger the temperature-sensitive skin sensors to lessen the symptoms, Dr. Johnson said.

An October 2021 study in Spain looked at 54 ED visits among 29 people with cannabinoid hyperemesis syndrome. For the 75% treated with capsaicin, vomiting stopped after an average of 18 minutes.

Lead author Guillermo Burillo-Putze, MD, PhD, said he is most surprised by the growing number of new cases of the disorder.

“This should be of concern given the increase in cannabis use due to its legalization and permissiveness,” said Dr. Burillo-Putze, an emergency doctor at Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Cannabinoid hyperemesis syndrome appears not to discriminate across racial and ethic groups. Although most studies to date include White participants, a July 2021 study of 29 people, 90% of whom were Black, found repeat visits to the ED were common.

The study found that 16 people returned 42 times to the ED and accounted for 10 hospital admissions, for example.
 

Cannabis conspiracy theories

“Unfortunately, this condition has become the subject of great speculation hinging on conspiracy theories as its true cause,” Dr. Russo noted in a September 2021 letter to the editor in the American Journal of Emergency Medicine.

Some “myth busting” is in order, he said.

For example, cannabinoid hyperemesis syndrome does not happen because of exposure to products from a tree called neem or from pesticides applied to marijuana plants during cultivation, Dr. Russo said. It can also occur with high-dose synthetic cannabinoids.
 

The state of recreational and medical marijuana

Recreational marijuana is legal in 18 states, Washington, D.C., and Guam as of January 2022, according to a report in U.S. News. More states permit medical marijuana use – 37 in total, plus Washington, D.C., according to Britannica ProCon.

One of the states where only medicinal use is legal is Maryland, which is where Dr. Vinocur practices.

“We are seeing increasing numbers of cases” of cannabinoid hyperemesis syndrome, she said.

In addition to chronic use or higher doses, it’s likely that the higher potency levels of THC in the legal marijuana industry trigger the syndrome in some people as well.

Linda estimates she ended up in emergency rooms at least a half-dozen times in the last 5 years. In April 2021, she had a “pretty serious event.” She blames it on traveling a lot for work, not eating right, and not getting enough sleep. She broke her 2-year abstinence with alcohol.

“I basically didn’t listen to my body and paid a pretty significant price for it,” she said.

Linda did not stop altogether but said she “drastically changed the types and form of the cannabis I was using.”

“I can tell you on the record that I would be a hundred percent dead without this plant,” she said.

“The prospect of living without it was more detrimental to me than all of those things I just described to you, because addiction runs in my family and I had opiate problems myself that I overcame with cannabis.”

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

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Motionless, every Olympic skater starts off perfectly. Once the music starts, it’s up to them whether they will continue on perfectly or not. In this way, you’re just like an Olympic skater. Each day, a skating program. The music starts the moment your foot touches the floor in the morning. It’s up to you if the rest of the day will continue on flawlessly or not. To this point, I’ve yet to have a perfect day.

If I’m honest, my “perfect day” streak typically ends once I’ve made coffee. By then, I’ll have spilled a few grains of grounds or clinked mugs together when taking one from the cupboard. (D’oh!) Hardly ever can I make it to backing out of the driveway, let alone through a patient encounter. I’ve had a few procedures that when complete I’ve thought, “well, that looks great.” I can remember encounters that went brilliantly despite a high technical difficulty. I’ve also tagged a 7-iron shot 160 downwind yards to within inches of the cup. But I’ve hardly ever done anything in my life perfectly.

What does it mean to be perfect? Well, there have been 23 perfect baseball games. In 1972, the Miami Dolphins had the only perfect NFL season, 14-0 (although my 2007 Patriots went 18-0 before losing to the – ugh – Giants). Every year, several hundred students score a perfect 1600 on the SAT. In an underground vault somewhere in France is a perfect sphere, a perfectly spherical 1-kg mass of pure silicon. There are at least 51 perfect numbers. And model Bella Hadid’s exactly 1.62-ratioed face is said to be perfectly beautiful. But yet, U.S. skater Nathan Chen’s seemingly flawless 113.97-point short program in Beijing, still imperfect.

Attempting a perfect day or perfect surgery or a perfect pour over coffee is a fun game, but perfectionism has an insidious side. Having perfectionistic concerns significantly increases the risk for burnout, depression, and eating disorders. Some of us feel this way every day: We must do it exactly right, every time. Even an insignificant imperfection or error feels like failure. A 3.90 GPA is a fail. 515 on the MCAT, not nearly good enough. For them, the burden of perfection is crushing. It is hard for some to recognize that even if your performance could not be improved, the outcome can still be flawed. A chip in the ice, a patient showing up late, an interviewer with an agenda, a missed referee call can all flub up an otherwise flawless day. It isn’t necessary to abandon hope, all ye who live in the real world. Although achieving perfection is usually impossible, reward comes from the pursuit of perfection, not from holding it. It is called perfectionistic striving and in contrast to perfectionistic concerns, it is associated with resilience and positive mood. To do so you must combine giving your all with acceptance of whatever the outcome.

Keith Jarrett is one of the greatest jazz pianists of all time. He is a true perfectionist, precise in his standards and exacting in expectations. In 1975 in Cologne, Germany, he agreed to play at the behest of a teenage girl who arranged to have him perform at the opera house. Except, there was a miscommunication and only a small, broken rehearsal piano was available. As the story goes, she approached him as he waited to be taken back to his hotel, the concert was canceled and she somehow convinced him to play on the nearly unplayable instrument. The result is the Köln Concert, one of the greatest jazz performances in history. It was perfectly imperfect.

Yes, even the 1-kg sphere has femtogram quantities of other elements mixed in – the universal standard for perfect is itself, imperfect. It doesn’t matter. It’s the pursuit of such that makes life worthwhile. There’s always tomorrow. Have your coffee grinders ready.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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