Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent reporting has shown that the number of physician-scientists — doctors who both practice medicine and perform scientific research — in the United States is dropping rapidly. That’s a problem, because physician-scientists are uniquely equipped to make scientific discoveries in the laboratory and translate them to the clinic. Indeed, many of the discoveries that have transformed medicine for the better were made by physician-scientists. For example, Jonas Salk developed the polio vaccine, Timothy Ley sequenced the first cancer genome, and Anthony Fauci coordinated public health responses to both the HIV/AIDS and COVID-19 pandemics. Indicative of their sheer impact, at least a third and as many as half of all Nobel Prizes and Lasker Awards in physiology/medicine have gone to physician-scientists.

So why is the supply of physician-scientists shrinking so precipitously at a time when medical discoveries are being made at a record-high rate? Immunotherapy and proton therapy are transforming cancer care; RNA technology led to COVID vaccines; CRISPR is facilitating gene editing and treatment of diseases like sickle cell anemia. Yet, as exciting as medical science has become, only 1.5% of American doctors work as physician-scientists, more than a threefold drop compared with 30 years ago when the figure was a more robust 4.7%. What’s going on?

Residency training programs at prestigious academic medical centers have standard infolded research years; for example, neurosurgery residents at academic medical centers will often get 2 years of protected research time. And the National Institutes of Health has training grants dedicated to physician-scientists, such as the K08 award program. Several foundations are also dedicated to supporting early-career physician-scientists. Yet, the number of physicians deciding to become physician-scientists remains low, and, more troubling, the attrition rate of those who do decide to go this route is quite high.

The underlying issue is multifold. First, funding rates from the federal government for grants have become competitive to the point of being unrealistic. For example, the current funding rate for the flagship R01 program from the National Cancer Institute is only 12%. Promotions are typically tied to these grant awards, which means physician-scientists who are unable to acquire substantial grant funding are unable to pay for their research or win promotion — and often exit the physician-scientist track altogether.

Compounding this issue is a lack of mentorship for early-career physician-scientists. With the rise of “careerism” in medicine, senior-level physician-scientists may have less incentive to mentor those who are earlier in their careers. Rather, there seems to be greater reward to “managing up” — that is, spending time to please hospital administrators and departmental leadership. Being involved in countless committees appears to carry more value in advancing an established investigator’s career than does mentorship.

Finally, physician-scientists typically earn less than their clinician colleagues, despite juggling both scientific and clinical responsibilities. While many are comfortable with this arrangement when embarking on this track, the disparity may become untenable after a while, especially as departmental leadership will often turn to physician-scientists to fill clinical coverage gaps when faculty leave the department, or as the medical center expands to satellite centers outside the primary hospital. Indeed, physician-scientists get pulled in several directions, which can lead to burnout and attrition, with many who are highly equipped for this track ultimately hanging up their cleats and seeking more clinical or private industry–oriented opportunities.

Every academic medical center operates differently. Some clearly have done a better job than others promoting and fostering physician-scientists. What we find in the centers that manage to retain physician-scientists is leadership plays a major role: If a medical center values the importance of physician-scientists, they will do things to foster the success of those people, such as assembling mentorship committees, establishing clear criteria for promotion and career advancement, protecting research time while maintaining some level of pay equity, advocating for team science approaches, and supporting investigators in cases of gaps in federal funding. Different countries also have different models for physician-scientist training, with Germany, for example, allowing medical residents to have 3 years of protected time to engage in research after their second year of residency.

The stakes here are high. If we can’t address the physician-scientist recruitment and retention crisis in America now, we risk falling behind other countries in our ability to innovate and deliver world-class care.

Dr Chaudhuri is a tenure-track physician-scientist at Washington University in St. Louis, a Paul and Daisy Soros Fellow, and a Public Voices Fellow of The OpEd Project.

Aadel Chaudhuri, MD, PhD, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Symptoms of anxiety and depression increased in adults living in trigger states that immediately banned abortions after the US Supreme Court Dobbs decision overturned Roe v. Wade, which revoked a woman’s constitutional right to an abortion, new research shows.

This could be due to a variety of factors, investigators led by Benjamin Thornburg, Johns Hopkins Bloomberg School of Public Health, Baltimore, noted. These include fear about the imminent risk of being denied an abortion, uncertainty around future limitations on abortion and other related rights such as contraception, worry over the ability to receive lifesaving medical care during pregnancy, and a general sense of violation and powerlessness related to loss of the right to reproductive autonomy.

The study was published online on January 23, 2024, in JAMA. 
 

Mental Health Harm

In June 2022, the US Supreme Court overturned Roe vs Wade, removing federal protections for abortion rights. Thirteen states had “trigger laws” that immediately banned or severely restricted abortion — raising concerns this could negatively affect mental health.

The researchers used data from the Household Pulse Survey to estimate changes in anxiety and depression symptoms after vs before the Dobbs decision in nearly 160,000 adults living in 13 states with trigger laws compared with roughly 559,000 adults living in 37 states without trigger laws.

The mean age of respondents was 48 years, and 51% were women. Anxiety and depression symptoms were measured via the Patient Health Questionnaire-4 (PHQ-4). 

In trigger states, the mean PHQ-4 score at baseline (before Dobbs) was 3.51 (out of 12) and increased to 3.81 after the Dobbs decision. In nontrigger states, the mean PHQ-4 score at baseline was 3.31 and increased to 3.49 after Dobbs.

Living in a trigger state was associated with a small but statistically significant worsening (0.11-point; P < .001) in anxiety/depression symptoms following the Dobbs decision vs living in a nontrigger state, the investigators report.

Women aged 18-45 years faced greater worsening of anxiety and depression symptoms following Dobbs in trigger vs nontrigger states, whereas men of a similar age experienced minimal or negligible changes. 
 

Implications for Care 

In an accompanying editorial, Julie Steinberg, PhD, with University of Maryland in College Park, notes the study results provide “emerging evidence that at an individual level taking away reproductive autonomy (by not having legal access to an abortion) may increase symptoms of anxiety and depression in all people and particularly females of reproductive age.”

These results add to findings from two other studies that examined abortion restrictions and mental health outcomes. Both found that limiting access to abortion was associated with more mental health symptoms among females of reproductive age than among others,” Dr. Steinberg pointed out.

“Together these findings highlight the need for clinicians who practice in states where abortion is banned to be aware that female patients of reproductive age may be experiencing significantly more distress than before the Dobbs decision,” Dr. Steinberg added. 

The study received no specific funding. The authors had no relevant conflicts of interest. Dr. Steinberg reported serving as a paid expert scientist on abortion and mental health in seven cases challenging abortion policies.

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

Newly released documents show that the US Food and Drug Administration (FDA) has determined that cannabis has a legitimate medical use and that it should be moved from Schedule I to Schedule III on the controlled substances list.

The FDA’s recommendation was contained in a 252-page report that was sent to the US Drug Enforcement Administration (DEA) in August 2023. The report, which Bloomberg News reported on in late August and may have been leaked to that news outlet, was released to Houston attorney Matthew Zorn. He filed suit in September to pressure the FDA to make its recommendation public. The FDA responded days before a court-ordered deadline, said Zorn.

The attorney was not representing any client. “This document belongs in the public sphere,” Zorn told this news organization. “I found it farcical that public policy was being debated on the basis of a document recommendation that literally no one had seen,” he said.

The Bloomberg report ignited debate, but no other advocate, attorney, or news organization had been able to obtain an unredacted version of FDA’s recommendation. 

Now that the full report is public, the DEA may be under more pressure to act. However, it is not required to do anything, and there is no set timeline for any action. Still, lawyers expect to quickly see a rule proposing moving cannabis from Schedule I to III.

“I expect it to come fairly soon and the reason I expect that is because the President told the agencies to do this expeditiously,” said Shane Pennington, an attorney with Porter Wright who has worked with Zorn on cases challenging DEA’s scheduling process but was not involved in this suit.

In October 2022, President Joe Biden said that he was asking the Department of Health and Human Services and the US Attorney General “to review expeditiously how marijuana is scheduled under federal law.”

Howard Sklamberg, a lawyer with Arnold & Porter in Washington, DC, said that the Biden directive “certainly made the agencies reconsider” rescheduling cannabis but that it likely was going to happen anyway, given a wealth of supportive information generated since the DEA last rejected a rescheduling petition in 2016. 

Mr. Sklamberg told this news organization that he thought a proposed rule would be issued soon, with a final rule issued by mid-summer. 

“Agencies generally want to get their important rulemaking done before you get too much into the political season and the potential end of a presidency,” said Mr. Sklamberg, a former FDA deputy commissioner.
 

Credible Medical Use

The FDA said in its report that cannabis is a low-risk threat to public health and that it poses less potential for misuse than drugs in schedule I or II, such as heroin or cocaine.

Though the evidence showed that some people are using cannabis “in amounts sufficient to create a hazard to their health and to the safety of other individuals and the community evidence also exists showing that the vast majority of individuals who use marijuana are doing so in a manner that does not lead to dangerous outcomes to themselves or others,” the FDA noted. 

The agency stated that “the risks to the public health posed by marijuana are low compared to other drugs of abuse (e.g., heroin, cocaine, benzodiazepines), based on an evaluation of various epidemiological databases for [emergency department] visits, hospitalizations, unintentional exposures, and most importantly, for overdose deaths.”

The FDA assessed cannabis’s commonly accepted medical use in seven indications: anorexia, anxiety, epilepsy, inflammatory bowel disease, nausea and vomiting, pain, and posttraumatic stress disorder. It concluded that the strongest evidence existed for anorexia related to a medical condition, nausea and vomiting, and pain.

Of interest, the agency said that when it assessed the harms and benefits, it also used alcohol as a comparator even though it is not a controlled substance. The agency said that it did so because of alcohol’s extensive availability and use, “which is also observed for nonmedical use of marijuana.” 

Mr. Sklamberg found that interesting. A majority of adults have consumed cannabis or know someone who has, making it similar to alcohol, he said. And just as with alcohol, “those adults have formed their own conclusions about what marijuana is and what it isn’t,” he said.

“A lot of Americans make their judgment and think schedule I overstates the health risks,” he added.
 

Opposition in Congress 

It is not certain whether cannabis will be rescheduled; after the Bloomberg report in August, Republican members of Congress sent a letter to DEA Administrator Anne Milgram telling her that the agency should not reschedule the drug.

“The recommendation to remove cannabis from the DEA’s list of dangerous Schedule I drugs is not based on science — it’s based on an irresponsible pro-pot agenda,” said Oklahoma Senator James Lankford (R) on X, in September.

The letter contended that there is no accepted medical use for cannabis and that “the known facts about marijuana have not changed since 2016.”

The FDA, however, based its recommendations in part in looking at data from more than 30,000 healthcare providers and six million patients who have used medical marijuana in state programs, largely established since 2016. Congress has directed the agency to evaluate more of that kind of real-world evidence when evaluating products, said Mr. Sklamberg.

He said that the FDA report will be taken seriously: “It’s a thorough and impressive document.”

“It’s not a document that looks like it was just put together by policy people or political people,” Mr. Sklamberg added. “It’s heavily grounded in science and medicine.”

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening strategy in postmenopausal women demonstrated a high specificity, sensitivity, and positive predictive value for detecting ovarian and borderline cancer, with most identified as stage I or II disease, a new analysis with a 21-year follow-up found.

METHODOLOGY:

• Detecting ovarian cancer at stage I or II could significantly reduce ovarian cancer-related deaths, but only 25%-30% of patients are diagnosed at an early stage.
• In this single-arm prospective analysis, 7,856 healthy postmenopausal women received annual screening for ovarian cancer between 2011 and 2022. Screening involved an annual blood test to detect levels of cancer antigen 125 and track these levels over time.
• Investigators used the Risk of Ovarian Cancer Algorithm (ROCA) to determine whether ovarian cancer risk was normal, intermediate, or high. Those with elevated ROCA scores were referred for transvaginal sonography; those with intermediate scores received follow-up blood tests every 3 months.
• Overall, 92.3% of women were normal risk, 5.7% were intermediate, and 2% were high risk and recommended for transvaginal sonography.

TAKEAWAY:

• Most women (95.5%) referred for transvaginal ultrasound had one. Of these ultrasounds, most (90%) were negative or revealed benign findings, 5.2% required a repeat ultrasound, and 4.8% (34 patients) showed suspicious findings.
• Of 34 patients with suspicious findings and recommended for surgery, 15 had ovarian cancer and two had borderline tumors, indicating a positive predictive value of 50% (17 of 34 patients) for ovarian cancer. Of these 17 patients, 12 (70.6%) had stage I or II disease.
• Following abnormal ROCA results, seven other women were diagnosed with endometrial tumors (six of which were stage I), indicating a positive predictive value of 74% (25 of 34) for any cancer.
• The specificity for elevated risk ROCA prompting ultrasound was 98%, and the specificity of the ROCA and ultrasound prompting surgery was 99.8%. The sensitivity for detecting ovarian and borderline cancer was 74% (17 of 23).

IN PRACTICE:

“Remarkably, 70% of ovarian cancers detected by the ROCA” were early stage,” the authors concluded. Although the trial was not powered to detect reduced mortality, the high specificity, positive predictive value, and shift to identifying earlier-stage cancers “support further development of this strategy,” the investigators said.

LIMITATIONS:

This trial was not powered to detect mortality benefit. Six ovarian cancers and borderline tumors were missed. Only 80% of ovarian cancers express cancer antigen 125, potentially limiting the sensitivity of the algorithm.

SOURCE:

This study, led by Chae Young Han from the University of Texas MD Anderson Cancer Center, Houston, was published online on January 12 in the Journal of Clinical Oncology.

DISCLOSURES:

This study was supported by funds from the NCI Early Detection Research Network, the MD Anderson Ovarian SPOREs, the National Cancer Institute, the Department of Health and Human Services, and others. The authors reported receiving research funding, grants, consulting, and personal fees from various companies, including Curio Science, Fujirebio Diagnostics, GlaxoSmithKline, AstraZeneca, and Genentech.

A version of this article appeared on Medscape.com.

In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).

The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.

Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.

“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.

Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.

“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.

Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.

To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
 

Methods and Results

In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.

Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.

Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.

At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.

All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.

In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).

However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.

In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.

In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
 

Results May Be ‘Hypothesis-Generating’

Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.

“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.

Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.

Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.

“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.

The ABACUS trial was supported by Roche.

In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).

The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.

Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.

“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.

Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.

“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.

Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.

To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
 

Methods and Results

In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.

Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.

Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.

At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.

All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.

In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).

However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.

In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.

In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
 

Results May Be ‘Hypothesis-Generating’

Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.

“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.

Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.

Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.

“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.

The ABACUS trial was supported by Roche.

In ongoing efforts to better understand the predictive value of circulating tumor DNA (ctDNA) in cancer treatment response, new research shows ctDNA clearance following neoadjuvant treatment of muscle-invasive urothelial cancer is a better predictor of the risk of relapse than a 50% reduction in ctDNA variant allele frequency (VAF).

The combination of ctDNA with other baseline biomarkers shows further accuracy in predicting treatment response, the study also shows.

Matthew Nicholas Young, MD, of Barts Cancer Institute, London, presented the research at the ASCO Genitourinary Cancers Symposium.

“We found that ctDNA and tissue-based biomarkers improved biomarker accuracy,” Dr. Young, first author of the study, said at the meeting.

Furthermore, “ctDNA clearance is rare but appears more accurate than 50% reduction in VAF to predict response/relapse,” the authors said in their abstract.

“This is relevant for ongoing neoadjuvant trials planning to use this as an endpoint,” they wrote.

Dr. Young and his colleagues have previously shown ctDNA clearance to be an important predictive marker of treatment response or relapse.

To better understand the predictive value in combination with other biomarkers, as well as whether a reduction in ctDNA variant allele frequency could be used as a surrogate predictor of relapse compared with ctDNA clearance, the authors conducted an exploratory biomarker analysis of the phase 2, multicenter ABACUS trial.
 

Methods and Results

In the study, 95 patients with inoperable, muscle-invasive urothelial cancer who were either not eligible for or refused neoadjuvant cisplatin-based chemotherapy, each received two cycles of atezolizumab, followed by radical cystectomy.

Previously published results show the study met its primary endpoint of a pathological complete response (pCR) of 31%, and the 2-year disease-free survival and overall survival rates were 68% and 77%, respectively.

Of the 95 patients, 40 had sequential DNA analysis that could be evaluated in the current analysis; 43% of those patients achieved a pCR, while 20% experienced a relapse.

At baseline, 63% of patients were ctDNA-positive, and after treatment, 8% achieved ctDNA clearance, while 40% had a ctDNA response of a 50% VAF reduction.

All patients who had ctDNA clearance achieved pCR and none relapsed. In comparison, 30% of patients with a 50% VAF reduction experienced relapse and only 40% achieved pCR.

In terms of correlations with baseline biomarkers, the combination of ctDNA with activated T cells was significantly associated with outcomes (P = .02), as was the combination with PDL-1 status (P = .004).

However, combination with tumor mutation burden, already weak as a predictive biomarker, remained weak when combined with ctDNA status (P = .2), Dr. Young reported.

In terms of baseline expression of ctDNA, patients who were positive at baseline showed an increase in innate and adaptive immune signaling, in a profile aligning with increased PD-L1 at baseline in ctDNA-positive patients.

In addition, decreased immune signaling was observed in ctDNA-positive patients who relapsed.
 

Results May Be ‘Hypothesis-Generating’

Asked during the session whether the results imply that patients with no detectable ctDNA prior to the start of therapy may not need or benefit from neoadjuvant therapy, Dr. Young said the small sample size of ctDNA patients in the study was an important limitation.

“I think [the results] are hypothesis-generating, as we know that some patients will not benefit from neoadjuvant therapy and the goal of this work is to try to identify patterns among those who may not need treatment,” he said.

Of the patients with ctDNA analysis, “only those who were ctDNA-positive at baseline relapsed, [as well as] those who were ctDNA-positive following cystectomy, so I think [the possibility that a lack of detectable ctDNA prior to the start of therapy could suggest that the patient may not need or benefit from neoadjuvant therapy] is an interesting hypothesis that has come from this work,” Dr. Young said.

Overall, the findings show that, “in ctDNA-positive patients, increased immune signals appear to be associated with better outcomes with atezolizumab,” he concluded.

“Combining immune and circulating biomarkers may be required to accurately predict response to therapy,” Dr. Young added.

The ABACUS trial was supported by Roche.

Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.

Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)

Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.

Disclosures: The authors reported no conflicts of interest.

Source: Jensen T et al.  Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672

Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.

Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)

Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.

Disclosures: The authors reported no conflicts of interest.

Source: Jensen T et al.  Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672

Key clinical point: Diagnosis of eosinophilic esophagitis (EoE) leads to psychosocial burdens in pediatric patients, especially in patients with neurodevelopmental disorders.

Major finding: Patients with shorter disease duration (6-12 months) had a higher symptom burden (P = .03). Patients with neurodevelopmental disorders had significantly greater somatic symptoms and anxiety, lower quality of life scores, and greater sleep disordered breathing (P < .01 for all)

Study details: This study included 87 patients (age 8-18 years, mean age 12.8 years, 26% girls) who completed validated assessments of EoE symptoms, quality of life, somatization, and sleep disordered breathing during regular clinic visits. Of these, 14% had been diagnosed with a neurodevelopmental disorder.

Disclosures: The authors reported no conflicts of interest.

Source: Jensen T et al.  Sleep, anxiety, somatization, quality of life, and resilience in pediatric patients with eosinophilic esophagitis. Clin Transl Gastroenterol. 2024 (Jan 11). doi: 10.14309/ctg.0000000000000672

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

Prior to 2013, the backbone of hepatitis C virus (HCV) therapy was pegylated interferon (PEG) in combination with ribavirin (RBV). This year-long therapy was associated with significant side effects and abysmal cure rates. Although efficacy improved with the addition of first-generation protease inhibitors, cure rates remained suboptimal and treatment side effects continued to be significant.

Clinicians and patients needed better options and looked to the drug pipeline with hope. However, even among the most optimistic, the idea that HCV therapy could evolve into an all-oral option seemed a relative pipe dream.

The Sofosbuvir Revolution Begins

The Liver Meeting held in 2013 changed everything.

Several presentations featured compelling data with sofosbuvir, a new polymerase inhibitor that, when combined with RBV, offered an all-oral option to patients with genotypes 2 and 3, as well as improved efficacy for patients with genotypes 1, 4, 5, and 6 when it was combined with 12 weeks of PEG/RBV.

However, the glass ceiling of HCV care was truly shattered with the randomized COSMOS trial, a late-breaker abstract that revealed 12-week functional cure rates in patients receiving sofosbuvir in combination with the protease inhibitor simeprevir.

This phase 2a trial in treatment-naive and -experienced genotype 1 patients with and without cirrhosis showed that an all-oral option was not only viable for the most common strain of HCV but was also safe and efficacious, even in difficult-to-treat populations.

On December 6, 2013, the US Food and Drug Administration (FDA) approved sofosbuvir for the treatment of HCV, ushering in a new era of therapy.

Guidelines quickly changed to advocate for both expansive HCV screening and generous treatment. Yet, as this more permissive approach was being recommended, the high price tag and large anticipated volume of those seeking prescriptions were setting off alarms. The drug cost triggered extensive restrictions based on degree of fibrosis, sobriety, and provider type in an effort to prevent immediate healthcare expenditures.

Given its high cost, rules restricting a patient to only one course of sofosbuvir-based therapy also surfaced. Although treatment with first-generation protease inhibitors carried a hefty price of $161,813.49 per sustained virologic response (SVR), compared with $66,000-$100,000 for 12 weeks of all-oral therapy, its uptake was low and limited by side effects and comorbid conditions. All-oral treatment appeared to have few medical barriers, leading payers to find ways to slow utilization. These restrictions are now gradually being eliminated.

Because of high SVR rates and few contraindications to therapy, most patients who gained access to treatment achieved cure. This included patients who had previously not responded to treatment and prioritized those with more advanced disease.

This quickly led to a significant shift in the population in need of treatment. Prior to 2013, many patients with HCV had advanced disease and did not respond to prior treatment options. After uptake of all-oral therapy, individuals in need were typically treatment naive without advanced disease.

This shift also added new psychosocial dimensions, as many of the newly infected individuals were struggling with active substance abuse. HCV treatment providers needed to change, with increasing recruitment of advanced practice providers, primary care physicians, and addiction medication specialists.

Progress, but Far From Reaching Targets

Fast-forward to 2023.

Ten years after FDA approval, 13.2 million individuals infected with HCV have been treated globally, 82% with sofosbuvir-based regimens and most in lower-middle-income countries. This is absolutely cause for celebration, but not complacency.

In 2016, the World Health Assembly adopted a resolution of elimination of viral hepatitis by 2030. The World Health Organization (WHO) defined elimination of HCV as 90% reduction in new cases of infection, 90% diagnosis of those infected, 80% of eligible individuals treated, and 65% reduction of deaths by 2030.

Despite all the success thus far, the CDA Foundation estimates that the WHO elimination targets will not be achieved until after the year 2050. They also note that in 2020, over 50 million individuals were infected with HCV, of which only 20% were diagnosed and 1% annually treated.

The HCV care cascade, by which the patient journeys from screening to cure, is complicated, and a one-size-fits-all solution is not possible. Reflex testing (an automatic transition to HCV polymerase chain reaction [PCR] testing in the lab for those who are HCV antibody positive) has significantly improved diagnosis. However, communicating these results and linking a patient to curative therapy remain significant obstacles.

Models and real-life experience show that multiple strategies can be successful. They include leveraging the electronic medical record, simplified treatment algorithms, test-and-treat strategies (screening high-risk populations with a point-of-care test that allows treatment initiation at the same visit), and co-localizing HCV screening and treatment with addiction services and relinkage programs (finding those who are already diagnosed and linking them to treatment).

In addition, focusing on populations at high risk for HCV infection — such as people who inject drugs, men who have sex with men, and incarcerated individuals — allows for better resource utilization.

Though daunting, HCV elimination is not impossible. There are several examples of success, including in the countries of Georgia and Iceland. Although, comparatively, the United States remains behind the curve, the White House has asked Congress for $11 billion to fund HCV elimination domestically.

As we await action at the national level, clinicians are reminded that there are several things we can do in caring for patients with HCV:

• A one-time HCV screening is recommended in all individuals aged 18 or older, including pregnant people with each pregnancy.
• HCV antibody testing with reflex to PCR should be used as the screening test.
• Pan-genotypic all-oral therapy is recommended for patients with HCV. Cure rates are greater than 95%, and there are few contraindications to treatment.
• Most people are eligible for simplified treatment algorithms that allow minimal on-treatment monitoring.

Without increased screening and linkage to curative therapy, we will not meet the WHO goals for HCV elimination.

Dr. Reau is chief of the hepatology section at Rush University Medical Center in Chicago and a regular contributor to this news organization. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America, as well as educational chair of the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels. She disclosed ties with AbbVie, Gilead, Arbutus, Intercept, and Salix.

A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

“It’s a health emergency for society, with mortality rates at over 90%,” warned Professor Alfredo Carrato, MD, PhD, the chairperson of Pancreatic Cancer Europe.

Pancreatic cancer is the seventh most common type of cancer in Europe but is the fourth leading cause of cancer-related deaths, behind lung, colorectal, and breast cancers. By 2030, it is widely predicted to become the second most common cause of cancer mortality.

There are many challenges with pancreatic cancer: Lack of awareness, difficult to diagnose, no screening programs for the general population, poor survival rate, and limited treatment options.

Life expectancy at the time of diagnosis is just 4.6 months. Only 3% of people diagnosed with pancreatic cancer will survive for 5 years.

A 2024 systematic analysis in The Lancet suggested that people living in Western Europe are more likely to develop pancreatic cancer than those living anywhere else in the world.

Dr. Carrato, emeritus professor of medical oncology at the University of Alcalá, Madrid, Spain, wasn’t surprised. He told this news organization: “I think the lifestyle in Europe plays a part. We have all of the risk factors in society like obesity, our sedentary behavior, too much red meat consumption, and excess alcohol intake.”

Other risk factors include smoking, diabetes, chronic pancreatitis, and a family history.

The incidence of pancreatic cancer increases with age, so the longer life expectancy in Western Europe could also contribute to the region’s high rates.

A Silent Killer

Pancreatic cancer is difficult to identify. It is often asymptomatic. Symptoms that do show themselves, like back pain, weight loss, and nausea, are nonspecific and make early diagnosis challenging.

Professor Mattias Löhr from the Karolinska Institutet, Stockholm, Sweden, told this news organization: “It’s a dismal disease. It’s not accessible for any easy screening or surveillance. Even early diagnosis is too late with pancreatic cancer.”

There have been few advancements in patient outcomes over the past few decades.

Only about 20% of patients are suitable candidates for surgery that could prolong their lives.

Also, cancer reoccurs in two thirds of surgical candidates, said Dr. Carrato, and oncologists don’t know how to identify them in advance. “I have patients who survive 3 months and others who survive 4 or 5 years, so there’s a need to identify these subtypes at a molecular level for personalized, clinical, and translational research and therapies.”

Dr. Löhr agreed: “All of the medical therapies are not really working well enough for pancreatic cancer in sharp contrast to other cancers.”

How Can Rates Be Reduced?

“Pancreatic Cancer Europe is working in every EU state to try to raise awareness,” said Dr. Carrato. “We should have primary prevention programs to modify lifestyle risks. We also need funds for translational and clinical research. Secondary prevention isn’t possible yet as we haven’t identified the higher-risk population who would be the target for screening.”

Screening programs are available for the 10% of people who have a family history of pancreatic cancer. But, for the vast majority, there are no tests or screenings that allow for earlier detection.

“We need blood or stool tests that have high specificity and sensitivity that are cost-effective,” said Dr. Carrato.

“It’s a type of cancer with a particular and very aggressive biology. There is a lack of pancreatic tumor tissue for research, as many patients are diagnosed by fine-needle aspiration cytology. It’s a challenge for researchers. We have no biomarkers available to direct our decisions; no precision oncology,” he added. 

Still, there are some encouraging developments.

The European PANCAID project (pancreatic cancer initial detection via liquid biopsy) is trying to find biomarkers to screen at-risk groups for earlier diagnosis via a blood test.

Also, the European Union (EU)-funded PANCAIM project (pancreatic cancer artificial intelligence [AI] for genomics and personalized medicine) has developed an AI algorithm that detects small cancers in CT scans that even experienced radiologists might easily overlook.

The project’s head, Henkjan Huisman, is professor of medical imaging AI at Radboud University Medical Center, Nijmegen, the Netherlands. He told this news organization: “It’s an extremely important step, as 20% of people with pancreas cancer have the ability to undergo surgery, which means they might live substantially longer. We believe if the tumors are found earlier, thanks to the algorithm, they are smaller and more contained, and so substantially more than 20% of patients would be suitable for surgery, which would be a breakthrough.”

Dr. Löhr added that a messenger RNA vaccine is being developed in the United States to prevent pancreatic cancer from returning after surgery and is demonstrating encouraging results in its early trials.

The Road Toward Better Care

To improve cancer care in Europe, Dr. Carrato said: “Reference centers should be a requirement in health policy programs because the outcomes are much better than in centers which only perform fewer surgeries, and Pancreatic Cancer Europe is working with the EU in this direction.”

Finland is a country that appears to have succeeded in this regard. Its 2005 Health Care Act, for example, ensures that cancer patients are able to receive care in one of its five specialized hospitals.

More research funding is also needed. According to Pancreatic Cancer Europe, only 2% of EU funding on cancer is spent on pancreatic cancer.

The American Cancer Society’s Cancer Facts & Figures 2024 makes room for some optimism, with the 5-year survival rate in the United States jumping to 13% from 6% in the society’s 2014 report, as a result of earlier diagnoses and more personalized treatment. But, even with potentially longer survival rates, said Dr. Löhr, “we are still on the trajectory of pancreatic cancer being number two for cancer deaths by 2030.”

“We need more money on research, centralized surgery, and networking between European countries,” said Dr. Carrato. “This networking would need more money for prevention, better diagnosis, and treatment. The problem is pancreatic cancer incidence is increasing and mortality is also in parallel, and we are not making real progress in this scenario.”

A version of this article appeared on Medscape.com.

“It’s a health emergency for society, with mortality rates at over 90%,” warned Professor Alfredo Carrato, MD, PhD, the chairperson of Pancreatic Cancer Europe.

Pancreatic cancer is the seventh most common type of cancer in Europe but is the fourth leading cause of cancer-related deaths, behind lung, colorectal, and breast cancers. By 2030, it is widely predicted to become the second most common cause of cancer mortality.

There are many challenges with pancreatic cancer: Lack of awareness, difficult to diagnose, no screening programs for the general population, poor survival rate, and limited treatment options.

Life expectancy at the time of diagnosis is just 4.6 months. Only 3% of people diagnosed with pancreatic cancer will survive for 5 years.

A 2024 systematic analysis in The Lancet suggested that people living in Western Europe are more likely to develop pancreatic cancer than those living anywhere else in the world.

Dr. Carrato, emeritus professor of medical oncology at the University of Alcalá, Madrid, Spain, wasn’t surprised. He told this news organization: “I think the lifestyle in Europe plays a part. We have all of the risk factors in society like obesity, our sedentary behavior, too much red meat consumption, and excess alcohol intake.”

Other risk factors include smoking, diabetes, chronic pancreatitis, and a family history.

The incidence of pancreatic cancer increases with age, so the longer life expectancy in Western Europe could also contribute to the region’s high rates.

A Silent Killer

Pancreatic cancer is difficult to identify. It is often asymptomatic. Symptoms that do show themselves, like back pain, weight loss, and nausea, are nonspecific and make early diagnosis challenging.

Professor Mattias Löhr from the Karolinska Institutet, Stockholm, Sweden, told this news organization: “It’s a dismal disease. It’s not accessible for any easy screening or surveillance. Even early diagnosis is too late with pancreatic cancer.”

There have been few advancements in patient outcomes over the past few decades.

Only about 20% of patients are suitable candidates for surgery that could prolong their lives.

Also, cancer reoccurs in two thirds of surgical candidates, said Dr. Carrato, and oncologists don’t know how to identify them in advance. “I have patients who survive 3 months and others who survive 4 or 5 years, so there’s a need to identify these subtypes at a molecular level for personalized, clinical, and translational research and therapies.”

Dr. Löhr agreed: “All of the medical therapies are not really working well enough for pancreatic cancer in sharp contrast to other cancers.”

How Can Rates Be Reduced?

“Pancreatic Cancer Europe is working in every EU state to try to raise awareness,” said Dr. Carrato. “We should have primary prevention programs to modify lifestyle risks. We also need funds for translational and clinical research. Secondary prevention isn’t possible yet as we haven’t identified the higher-risk population who would be the target for screening.”

Screening programs are available for the 10% of people who have a family history of pancreatic cancer. But, for the vast majority, there are no tests or screenings that allow for earlier detection.

“We need blood or stool tests that have high specificity and sensitivity that are cost-effective,” said Dr. Carrato.

“It’s a type of cancer with a particular and very aggressive biology. There is a lack of pancreatic tumor tissue for research, as many patients are diagnosed by fine-needle aspiration cytology. It’s a challenge for researchers. We have no biomarkers available to direct our decisions; no precision oncology,” he added. 

Still, there are some encouraging developments.

The European PANCAID project (pancreatic cancer initial detection via liquid biopsy) is trying to find biomarkers to screen at-risk groups for earlier diagnosis via a blood test.

Also, the European Union (EU)-funded PANCAIM project (pancreatic cancer artificial intelligence [AI] for genomics and personalized medicine) has developed an AI algorithm that detects small cancers in CT scans that even experienced radiologists might easily overlook.

The project’s head, Henkjan Huisman, is professor of medical imaging AI at Radboud University Medical Center, Nijmegen, the Netherlands. He told this news organization: “It’s an extremely important step, as 20% of people with pancreas cancer have the ability to undergo surgery, which means they might live substantially longer. We believe if the tumors are found earlier, thanks to the algorithm, they are smaller and more contained, and so substantially more than 20% of patients would be suitable for surgery, which would be a breakthrough.”

Dr. Löhr added that a messenger RNA vaccine is being developed in the United States to prevent pancreatic cancer from returning after surgery and is demonstrating encouraging results in its early trials.

The Road Toward Better Care

To improve cancer care in Europe, Dr. Carrato said: “Reference centers should be a requirement in health policy programs because the outcomes are much better than in centers which only perform fewer surgeries, and Pancreatic Cancer Europe is working with the EU in this direction.”

Finland is a country that appears to have succeeded in this regard. Its 2005 Health Care Act, for example, ensures that cancer patients are able to receive care in one of its five specialized hospitals.

More research funding is also needed. According to Pancreatic Cancer Europe, only 2% of EU funding on cancer is spent on pancreatic cancer.

The American Cancer Society’s Cancer Facts & Figures 2024 makes room for some optimism, with the 5-year survival rate in the United States jumping to 13% from 6% in the society’s 2014 report, as a result of earlier diagnoses and more personalized treatment. But, even with potentially longer survival rates, said Dr. Löhr, “we are still on the trajectory of pancreatic cancer being number two for cancer deaths by 2030.”

“We need more money on research, centralized surgery, and networking between European countries,” said Dr. Carrato. “This networking would need more money for prevention, better diagnosis, and treatment. The problem is pancreatic cancer incidence is increasing and mortality is also in parallel, and we are not making real progress in this scenario.”

A version of this article appeared on Medscape.com.

“It’s a health emergency for society, with mortality rates at over 90%,” warned Professor Alfredo Carrato, MD, PhD, the chairperson of Pancreatic Cancer Europe.

Pancreatic cancer is the seventh most common type of cancer in Europe but is the fourth leading cause of cancer-related deaths, behind lung, colorectal, and breast cancers. By 2030, it is widely predicted to become the second most common cause of cancer mortality.

There are many challenges with pancreatic cancer: Lack of awareness, difficult to diagnose, no screening programs for the general population, poor survival rate, and limited treatment options.

Life expectancy at the time of diagnosis is just 4.6 months. Only 3% of people diagnosed with pancreatic cancer will survive for 5 years.

A 2024 systematic analysis in The Lancet suggested that people living in Western Europe are more likely to develop pancreatic cancer than those living anywhere else in the world.

Dr. Carrato, emeritus professor of medical oncology at the University of Alcalá, Madrid, Spain, wasn’t surprised. He told this news organization: “I think the lifestyle in Europe plays a part. We have all of the risk factors in society like obesity, our sedentary behavior, too much red meat consumption, and excess alcohol intake.”

Other risk factors include smoking, diabetes, chronic pancreatitis, and a family history.

The incidence of pancreatic cancer increases with age, so the longer life expectancy in Western Europe could also contribute to the region’s high rates.

A Silent Killer

Pancreatic cancer is difficult to identify. It is often asymptomatic. Symptoms that do show themselves, like back pain, weight loss, and nausea, are nonspecific and make early diagnosis challenging.

Professor Mattias Löhr from the Karolinska Institutet, Stockholm, Sweden, told this news organization: “It’s a dismal disease. It’s not accessible for any easy screening or surveillance. Even early diagnosis is too late with pancreatic cancer.”

There have been few advancements in patient outcomes over the past few decades.

Only about 20% of patients are suitable candidates for surgery that could prolong their lives.

Also, cancer reoccurs in two thirds of surgical candidates, said Dr. Carrato, and oncologists don’t know how to identify them in advance. “I have patients who survive 3 months and others who survive 4 or 5 years, so there’s a need to identify these subtypes at a molecular level for personalized, clinical, and translational research and therapies.”

Dr. Löhr agreed: “All of the medical therapies are not really working well enough for pancreatic cancer in sharp contrast to other cancers.”

How Can Rates Be Reduced?

“Pancreatic Cancer Europe is working in every EU state to try to raise awareness,” said Dr. Carrato. “We should have primary prevention programs to modify lifestyle risks. We also need funds for translational and clinical research. Secondary prevention isn’t possible yet as we haven’t identified the higher-risk population who would be the target for screening.”

Screening programs are available for the 10% of people who have a family history of pancreatic cancer. But, for the vast majority, there are no tests or screenings that allow for earlier detection.

“We need blood or stool tests that have high specificity and sensitivity that are cost-effective,” said Dr. Carrato.

“It’s a type of cancer with a particular and very aggressive biology. There is a lack of pancreatic tumor tissue for research, as many patients are diagnosed by fine-needle aspiration cytology. It’s a challenge for researchers. We have no biomarkers available to direct our decisions; no precision oncology,” he added. 

Still, there are some encouraging developments.

The European PANCAID project (pancreatic cancer initial detection via liquid biopsy) is trying to find biomarkers to screen at-risk groups for earlier diagnosis via a blood test.

Also, the European Union (EU)-funded PANCAIM project (pancreatic cancer artificial intelligence [AI] for genomics and personalized medicine) has developed an AI algorithm that detects small cancers in CT scans that even experienced radiologists might easily overlook.

The project’s head, Henkjan Huisman, is professor of medical imaging AI at Radboud University Medical Center, Nijmegen, the Netherlands. He told this news organization: “It’s an extremely important step, as 20% of people with pancreas cancer have the ability to undergo surgery, which means they might live substantially longer. We believe if the tumors are found earlier, thanks to the algorithm, they are smaller and more contained, and so substantially more than 20% of patients would be suitable for surgery, which would be a breakthrough.”

Dr. Löhr added that a messenger RNA vaccine is being developed in the United States to prevent pancreatic cancer from returning after surgery and is demonstrating encouraging results in its early trials.

The Road Toward Better Care

To improve cancer care in Europe, Dr. Carrato said: “Reference centers should be a requirement in health policy programs because the outcomes are much better than in centers which only perform fewer surgeries, and Pancreatic Cancer Europe is working with the EU in this direction.”

Finland is a country that appears to have succeeded in this regard. Its 2005 Health Care Act, for example, ensures that cancer patients are able to receive care in one of its five specialized hospitals.

More research funding is also needed. According to Pancreatic Cancer Europe, only 2% of EU funding on cancer is spent on pancreatic cancer.

The American Cancer Society’s Cancer Facts & Figures 2024 makes room for some optimism, with the 5-year survival rate in the United States jumping to 13% from 6% in the society’s 2014 report, as a result of earlier diagnoses and more personalized treatment. But, even with potentially longer survival rates, said Dr. Löhr, “we are still on the trajectory of pancreatic cancer being number two for cancer deaths by 2030.”

“We need more money on research, centralized surgery, and networking between European countries,” said Dr. Carrato. “This networking would need more money for prevention, better diagnosis, and treatment. The problem is pancreatic cancer incidence is increasing and mortality is also in parallel, and we are not making real progress in this scenario.”

A version of this article appeared on Medscape.com.