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Langya, a new zoonotic virus, detected in China
Between 2018 and August 2022, These cases were reported in The New England Journal of Medicine. When asked by Nature about this emerging virus that has until now flown under the radar, scientists said that they were not overly concerned because the virus doesn’t seem to spread easily between people nor is it fatal.
Researchers think that the virus is carried by shrews. It might have infected people directly or through an intermediate animal.
First identified in Langya
The authors describe 35 cases of infection with a virus called Langya henipavirus (LayV) since 2018. It is closely related to two other henipaviruses known to infect people – Hendra virus and Nipah virus. The virus was named Langya after the town in Shandong province in China where the first patient identified with the disease was from, explained coauthor Linfa Wang, PhD, a virologist at Duke-NUS Medical School, Singapore.
Langya can cause respiratory symptoms such as fever, cough, and fatigue. Hendra virus and Nipah virus also cause respiratory infections and can be fatal, the article in Nature reports.
Hendra and Nipah
According to the World Health Organization, Nipah virus, which was discovered in 1999, is a new virus responsible for a zoonosis that causes the disease in animals and humans who have had contact with infected animals. Its name comes from the location where it was first identified in Malaysia. Patients may have asymptomatic infection or symptoms such as acute respiratory infection and severe encephalitis. The case fatality rate is between 40% and 75%.
Nipah virus is closely related to another recently discovered (1994) zoonotic virus called Hendra virus, which is named after the Australian city in which it first appeared. On that day in July 2016, 53 cases were identified involving 70 horses. These incidents remained confined to the northeastern coast of Australia.
Nipah virus and Hendra virus belong to the Paramyxoviridae family. “While the members of this group of viruses are only responsible for a few limited outbreaks, the ability of these viruses to infect a wide range of hosts and cause a disease leading to high fatalities in humans has made them a public health concern,” stated the WHO.
Related to measles
The research team identified LayV while monitoring patients at three hospitals in the eastern Chinese provinces of Shandong and Henan between April 2018 and August 2021. Throughout the study period, the researchers found 35 people infected with LayV, mostly farmers, with symptoms ranging from a cough to severe pneumonia. Participants were recruited into the study if they had a fever. The team sequenced the LayV genome from a throat swab taken from the first patient identified with the disease, a 53-year-old woman.
The LayV genome showed that the virus is most closely related to Mojiang henipavirus, which was first isolated in rats in an abandoned mine in the southern Chinese province of Yunnan in 2012. Henipaviruses belong to the Paramyxoviridae family of viruses, which includes measles, mumps, and many respiratory viruses that infect humans. Several other henipaviruses have been discovered in bats, rats, and shrews from Australia to South Korea and China, but only Hendra, Nipah, and now LayV are known to infect people, according to Nature.
Animal origin likely
Because most patients stated in a questionnaire that they had been exposed to an animal during the month preceding the onset of their symptoms, the researchers tested goats, dogs, pigs, and cattle living in the villages of infected patients for antibodies against LayV. They found LayV antibodies in a handful of goats and dogs and identified LayV viral RNA in 27% of the 262 sampled shrews. These findings suggest that the shrew may be a natural reservoir of LayV, passing it between themselves “and somehow infecting people here and there by chance,” Emily Gurley, PhD, MPH, an infectious diseases epidemiologist at Johns Hopkins University, Baltimore, told Nature.
The researchers did not find strong evidence of LayV spreading between the people included in the study. There were no clusters of cases in the same family, within a short time span, or in close geographical proximity. “Of the 35 cases, not a single one is linked,” said Dr. Wang, which Dr. Gurley considered good news. It should be noted, however ,”that the study did retrospective contact tracing on only 15 family members of nine infected individuals, which makes it difficult to determine how exactly the individuals were exposed,” reported Nature.
Vigilance is needed
Should we be worried about a potential new epidemic? The replies from two experts interviewed by Nature were reassuring. “There is no particular need to worry about this virus, but ongoing surveillance is critical,” said Professor Edward Holmes, an evolutionary virologist at the University of Sydney. Regularly testing people and animals for emerging viruses is important to understand the risk for zoonotic diseases – those that can be transmitted from other animals to humans, he said.
It is still not clear how people were infected in the first place – whether directly from shrews or an intermediate animal, said Dr. Gurley. That’s why a lot of research still needs to be done to work out how the virus is spreading in shrews and how people are getting infected, she added.
Nevertheless, Dr. Gurley finds that large outbreaks of infectious diseases typically take off after a lot of false starts. “If we are actively looking for those sparks, then we are in a much better position to stop or to find something early.” Still, she noted that she didn’t see anything in the data to “cause alarm from a pandemic-threat perspective.”
Though there is not currently any cause for worry of a new pandemic, vigilance is crucial. Professor Holmes says there is an urgent need for a global surveillance system to detect virus spillovers and rapidly communicate those results to avoid more pandemics, such as the one sparked by COVID-19. “These sorts of zoonotic spillover events happen all the time,” he said. “The world needs to wake up.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Between 2018 and August 2022, These cases were reported in The New England Journal of Medicine. When asked by Nature about this emerging virus that has until now flown under the radar, scientists said that they were not overly concerned because the virus doesn’t seem to spread easily between people nor is it fatal.
Researchers think that the virus is carried by shrews. It might have infected people directly or through an intermediate animal.
First identified in Langya
The authors describe 35 cases of infection with a virus called Langya henipavirus (LayV) since 2018. It is closely related to two other henipaviruses known to infect people – Hendra virus and Nipah virus. The virus was named Langya after the town in Shandong province in China where the first patient identified with the disease was from, explained coauthor Linfa Wang, PhD, a virologist at Duke-NUS Medical School, Singapore.
Langya can cause respiratory symptoms such as fever, cough, and fatigue. Hendra virus and Nipah virus also cause respiratory infections and can be fatal, the article in Nature reports.
Hendra and Nipah
According to the World Health Organization, Nipah virus, which was discovered in 1999, is a new virus responsible for a zoonosis that causes the disease in animals and humans who have had contact with infected animals. Its name comes from the location where it was first identified in Malaysia. Patients may have asymptomatic infection or symptoms such as acute respiratory infection and severe encephalitis. The case fatality rate is between 40% and 75%.
Nipah virus is closely related to another recently discovered (1994) zoonotic virus called Hendra virus, which is named after the Australian city in which it first appeared. On that day in July 2016, 53 cases were identified involving 70 horses. These incidents remained confined to the northeastern coast of Australia.
Nipah virus and Hendra virus belong to the Paramyxoviridae family. “While the members of this group of viruses are only responsible for a few limited outbreaks, the ability of these viruses to infect a wide range of hosts and cause a disease leading to high fatalities in humans has made them a public health concern,” stated the WHO.
Related to measles
The research team identified LayV while monitoring patients at three hospitals in the eastern Chinese provinces of Shandong and Henan between April 2018 and August 2021. Throughout the study period, the researchers found 35 people infected with LayV, mostly farmers, with symptoms ranging from a cough to severe pneumonia. Participants were recruited into the study if they had a fever. The team sequenced the LayV genome from a throat swab taken from the first patient identified with the disease, a 53-year-old woman.
The LayV genome showed that the virus is most closely related to Mojiang henipavirus, which was first isolated in rats in an abandoned mine in the southern Chinese province of Yunnan in 2012. Henipaviruses belong to the Paramyxoviridae family of viruses, which includes measles, mumps, and many respiratory viruses that infect humans. Several other henipaviruses have been discovered in bats, rats, and shrews from Australia to South Korea and China, but only Hendra, Nipah, and now LayV are known to infect people, according to Nature.
Animal origin likely
Because most patients stated in a questionnaire that they had been exposed to an animal during the month preceding the onset of their symptoms, the researchers tested goats, dogs, pigs, and cattle living in the villages of infected patients for antibodies against LayV. They found LayV antibodies in a handful of goats and dogs and identified LayV viral RNA in 27% of the 262 sampled shrews. These findings suggest that the shrew may be a natural reservoir of LayV, passing it between themselves “and somehow infecting people here and there by chance,” Emily Gurley, PhD, MPH, an infectious diseases epidemiologist at Johns Hopkins University, Baltimore, told Nature.
The researchers did not find strong evidence of LayV spreading between the people included in the study. There were no clusters of cases in the same family, within a short time span, or in close geographical proximity. “Of the 35 cases, not a single one is linked,” said Dr. Wang, which Dr. Gurley considered good news. It should be noted, however ,”that the study did retrospective contact tracing on only 15 family members of nine infected individuals, which makes it difficult to determine how exactly the individuals were exposed,” reported Nature.
Vigilance is needed
Should we be worried about a potential new epidemic? The replies from two experts interviewed by Nature were reassuring. “There is no particular need to worry about this virus, but ongoing surveillance is critical,” said Professor Edward Holmes, an evolutionary virologist at the University of Sydney. Regularly testing people and animals for emerging viruses is important to understand the risk for zoonotic diseases – those that can be transmitted from other animals to humans, he said.
It is still not clear how people were infected in the first place – whether directly from shrews or an intermediate animal, said Dr. Gurley. That’s why a lot of research still needs to be done to work out how the virus is spreading in shrews and how people are getting infected, she added.
Nevertheless, Dr. Gurley finds that large outbreaks of infectious diseases typically take off after a lot of false starts. “If we are actively looking for those sparks, then we are in a much better position to stop or to find something early.” Still, she noted that she didn’t see anything in the data to “cause alarm from a pandemic-threat perspective.”
Though there is not currently any cause for worry of a new pandemic, vigilance is crucial. Professor Holmes says there is an urgent need for a global surveillance system to detect virus spillovers and rapidly communicate those results to avoid more pandemics, such as the one sparked by COVID-19. “These sorts of zoonotic spillover events happen all the time,” he said. “The world needs to wake up.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
Between 2018 and August 2022, These cases were reported in The New England Journal of Medicine. When asked by Nature about this emerging virus that has until now flown under the radar, scientists said that they were not overly concerned because the virus doesn’t seem to spread easily between people nor is it fatal.
Researchers think that the virus is carried by shrews. It might have infected people directly or through an intermediate animal.
First identified in Langya
The authors describe 35 cases of infection with a virus called Langya henipavirus (LayV) since 2018. It is closely related to two other henipaviruses known to infect people – Hendra virus and Nipah virus. The virus was named Langya after the town in Shandong province in China where the first patient identified with the disease was from, explained coauthor Linfa Wang, PhD, a virologist at Duke-NUS Medical School, Singapore.
Langya can cause respiratory symptoms such as fever, cough, and fatigue. Hendra virus and Nipah virus also cause respiratory infections and can be fatal, the article in Nature reports.
Hendra and Nipah
According to the World Health Organization, Nipah virus, which was discovered in 1999, is a new virus responsible for a zoonosis that causes the disease in animals and humans who have had contact with infected animals. Its name comes from the location where it was first identified in Malaysia. Patients may have asymptomatic infection or symptoms such as acute respiratory infection and severe encephalitis. The case fatality rate is between 40% and 75%.
Nipah virus is closely related to another recently discovered (1994) zoonotic virus called Hendra virus, which is named after the Australian city in which it first appeared. On that day in July 2016, 53 cases were identified involving 70 horses. These incidents remained confined to the northeastern coast of Australia.
Nipah virus and Hendra virus belong to the Paramyxoviridae family. “While the members of this group of viruses are only responsible for a few limited outbreaks, the ability of these viruses to infect a wide range of hosts and cause a disease leading to high fatalities in humans has made them a public health concern,” stated the WHO.
Related to measles
The research team identified LayV while monitoring patients at three hospitals in the eastern Chinese provinces of Shandong and Henan between April 2018 and August 2021. Throughout the study period, the researchers found 35 people infected with LayV, mostly farmers, with symptoms ranging from a cough to severe pneumonia. Participants were recruited into the study if they had a fever. The team sequenced the LayV genome from a throat swab taken from the first patient identified with the disease, a 53-year-old woman.
The LayV genome showed that the virus is most closely related to Mojiang henipavirus, which was first isolated in rats in an abandoned mine in the southern Chinese province of Yunnan in 2012. Henipaviruses belong to the Paramyxoviridae family of viruses, which includes measles, mumps, and many respiratory viruses that infect humans. Several other henipaviruses have been discovered in bats, rats, and shrews from Australia to South Korea and China, but only Hendra, Nipah, and now LayV are known to infect people, according to Nature.
Animal origin likely
Because most patients stated in a questionnaire that they had been exposed to an animal during the month preceding the onset of their symptoms, the researchers tested goats, dogs, pigs, and cattle living in the villages of infected patients for antibodies against LayV. They found LayV antibodies in a handful of goats and dogs and identified LayV viral RNA in 27% of the 262 sampled shrews. These findings suggest that the shrew may be a natural reservoir of LayV, passing it between themselves “and somehow infecting people here and there by chance,” Emily Gurley, PhD, MPH, an infectious diseases epidemiologist at Johns Hopkins University, Baltimore, told Nature.
The researchers did not find strong evidence of LayV spreading between the people included in the study. There were no clusters of cases in the same family, within a short time span, or in close geographical proximity. “Of the 35 cases, not a single one is linked,” said Dr. Wang, which Dr. Gurley considered good news. It should be noted, however ,”that the study did retrospective contact tracing on only 15 family members of nine infected individuals, which makes it difficult to determine how exactly the individuals were exposed,” reported Nature.
Vigilance is needed
Should we be worried about a potential new epidemic? The replies from two experts interviewed by Nature were reassuring. “There is no particular need to worry about this virus, but ongoing surveillance is critical,” said Professor Edward Holmes, an evolutionary virologist at the University of Sydney. Regularly testing people and animals for emerging viruses is important to understand the risk for zoonotic diseases – those that can be transmitted from other animals to humans, he said.
It is still not clear how people were infected in the first place – whether directly from shrews or an intermediate animal, said Dr. Gurley. That’s why a lot of research still needs to be done to work out how the virus is spreading in shrews and how people are getting infected, she added.
Nevertheless, Dr. Gurley finds that large outbreaks of infectious diseases typically take off after a lot of false starts. “If we are actively looking for those sparks, then we are in a much better position to stop or to find something early.” Still, she noted that she didn’t see anything in the data to “cause alarm from a pandemic-threat perspective.”
Though there is not currently any cause for worry of a new pandemic, vigilance is crucial. Professor Holmes says there is an urgent need for a global surveillance system to detect virus spillovers and rapidly communicate those results to avoid more pandemics, such as the one sparked by COVID-19. “These sorts of zoonotic spillover events happen all the time,” he said. “The world needs to wake up.”
This article was translated from the Medscape French edition. A version appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Congressman’s wife died after taking herbal remedy marketed for diabetes and weight loss
The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.
Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.
The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”
Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.
It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.
Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.
“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.
Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.
“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”
Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.
Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.
The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”
Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.
Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.
At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”
“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”
According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”
Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.
If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.
“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.
The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.
Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.
Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.
While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.
White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.
White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.
Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.
Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.
The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.
Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.
But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.
Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.
“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”
The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.
Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.
Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.
But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.
“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”
It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.
“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.
Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.
The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”
Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.
It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.
Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.
“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.
Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.
“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”
Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.
Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.
The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”
Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.
Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.
At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”
“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”
According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”
Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.
If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.
“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.
The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.
Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.
Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.
While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.
White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.
White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.
Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.
Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.
The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.
Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.
But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.
Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.
“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”
The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.
Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.
Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.
But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.
“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”
It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.
“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
The wife of a Northern California congressman died late in 2021 after ingesting a plant that is generally considered safe and is used as an herbal remedy for a variety of ailments, including diabetes, obesity, and high cholesterol.
Lori McClintock, the wife of U.S. Rep. Tom McClintock, died from dehydration due to gastroenteritis – an inflammation of the stomach and intestines – that was caused by “adverse effects of white mulberry leaf ingestion,” according to a report from the Sacramento County coroner that is dated March 10 but was not immediately released to the public. KHN obtained that report – in addition to the autopsy report and an amended death certificate containing an updated cause of death – in July.
The coroner’s office ruled her death an accident. The original death certificate, dated Dec. 20, 2021, listed the cause of death as “pending.”
Tom McClintock, a Republican who represents a district that spans multiple counties in northern and central California, found his 61-year-old wife unresponsive at their Elk Grove, Calif., home on Dec. 15, 2021, according to the coroner’s report. He had just returned from Washington after voting in Congress the night before.
It’s unclear from the autopsy report whether Lori McClintock took a dietary supplement containing white mulberry leaf, ate fresh or dried leaves, or drank them in a tea, but a “partially intact” white mulberry leaf was found in her stomach, according to the report.
Ms. McClintock’s death underscores the risks of the vast, booming market of dietary supplements and herbal remedies, which have grown into a $54 billion industry in the United States – one that both lawmakers and health care experts say needs more government scrutiny.
“Many people assume if that product is sold in the United States of America, somebody has inspected it, and it must be safe. Unfortunately, that’s not always true,” U.S. Sen. Richard Durbin (D-Ill.) said on the Senate floor this spring when he introduced legislation to strengthen oversight of dietary supplements.
Daniel Fabricant, CEO and president of the Natural Products Association, which represents the dietary supplements industry, questioned whether Ms. McClintock’s death was related to a supplement.
“It’s completely speculative. There’s a science to this. It’s not just what a coroner feels,” said Mr. Fabricant, who oversaw dietary supplements at the Food and Drug Administration during the Obama administration. “People unfortunately pass from dehydration every day, and there’s a lot of different reasons and a lot of different causes.”
Mr. Fabricant said it would have been ideal had the coroner or the family reported her death to the FDA so the agency could have launched an investigation.
Such reports are voluntary, and it’s not clear whether anyone reported her death to the agency. FDA spokesperson Courtney Rhodes said the agency does not discuss possible or ongoing investigations.
The FDA, Mr. Fabricant added, has a system in place to investigate deaths that might be linked to a supplement or drug. “It’s casework,” he said. “It’s good, old-fashioned police work that needs to be done.”
Tom McClintock has remained mostly silent about his wife’s death since he released a statement on Dec. 19, 2021, announcing it and gave a tribute to her at her Jan. 4 funeral. Until now, the cause of death had not been reported.
Mr. McClintock, contacted multiple times by phone and email Wednesday, was not immediately available for comment.
At his wife’s funeral, McClintock told mourners that she was fine when he spoke with her the day before he returned. She had told a friend that “she was on a roll” at a new job she loved in a Sacramento real estate office, he said, and “she was carefully dieting.”
“She just joined a gym,” he said. “At home, she was counting down the days to Christmas, wrapping all the gifts and making all the plans to make it the best family Christmas ever, and it would have been.”
According to the coroner’s report, however, the day before her death, “she had complaints of an upset stomach.”
Sacramento County spokesperson Kim Nava said via email Wednesday that the law prohibits the coroner’s office from discussing many details of specific cases. As part of any death investigation, the office “attempts to locate and review medical records and speak to family/witnesses to establish events leading up to and surrounding a death,” she said.
If any medications or supplements are found at the scene or if pertinent information is in the person’s medical records, those are passed along to the pathologist to help establish cause of death, Ms. Nava said.
“Any information the office obtains from medical records can’t be disseminated to a third party except by court order,” she said.
The leaves and fruit of the white mulberry tree, which is native to China, have been used for centuries in traditional medicine. Academic studies over the past decade have found that the extract from its leaves can lower blood sugar levels and help with weight loss. People take it in capsule or pill form, as an extract or powder. They can also brew the leaves as an herbal tea.
Lori McClintock’s reaction seems unusual. No deaths from the white mulberry plant have been reported to poison control officials in the past 10 years, according to the American Association of Poison Control Centers.
Since 2012, 148 cases of white mulberry plant ingestion were voluntarily reported to poison control officials nationally, most involving accidental ingestion by children 12 and under, said Kaitlyn Brown, clinical managing director for the association. Only one case required medical follow-up, she said.
While poison control centers track exposures to the white mulberry plant, the FDA oversees dietary supplements, such as products that contain white mulberry leaf extract. Since 2004, two cases of people sickened by mulberry supplements have been reported to the FDA, according to its database that tracks “adverse events.” It relies heavily on voluntary reports from health care professionals and consumers. At least one of those cases led to hospitalization.
White mulberry leaf can have side effects, including nausea and diarrhea, according to research. Independent lab tests ordered by the coroner’s office showed Ms. McClintock’s body had elevated levels of nitrogen, sodium, and creatinine – all signs of dehydration, according to three pathologists who reviewed the coroner’s documents, which KHN redacted to remove Ms. McClintock’s name.
White mulberry leaves “do tend to cause dehydration, and part of the uses for that can be to help someone lose weight, mostly through fluid loss, which in this case was just kind of excessive,” said D’Michelle DuPre, MD, a retired forensic pathologist and a former medical examiner in South Carolina who reviewed the documents.
Dietary supplements, which include a broad range of vitamins, herbs, and minerals, are regulated by the FDA. However, they are classified as food and don’t undergo the rigorous scientific and safety testing the government requires of prescription drugs and over-the-counter medicines.
Lawmakers aren’t proposing to put supplements into the same category as pharmaceuticals, but some say they are alarmed that neither the FDA nor the industry knows how many dietary supplements are out there – making it almost impossible for the government to oversee them and punish bad actors.
The FDA estimates 40,000 to 80,000 supplement products are on the market in the United States, and industry surveys estimate 80% of Americans use them.
Legislation by Sen. Durbin and U.S. Sen. Mike Braun (R-Ind.) would require manufacturers to register with the FDA and provide a public list of ingredients in their products, two provisions that are backed by the Council for Responsible Nutrition, another industry group that represents supplement makers.
But the council is lobbying against a provision that would require supplement makers to provide consumers with the ingredient amounts – or the blend – in their products, something they say is akin to giving a recipe to competitors. That’s proprietary information only government regulators should have access to, said Megan Olsen, the group’s senior vice president and general counsel.
Ms. Olsen explained that supplement manufacturers are regulated just like other food companies and are subject to strict labeling requirements and inspections by the FDA. They also must inform the agency about any adverse effects reported by consumers or doctors.
“Companies are testing products throughout the process, are reviewing how they’re being manufactured and what’s going into them,” Ms. Olsen said. “All of that is overseen and dictated by FDA regulation.”
The dietary supplement provisions were rolled into a larger Senate health committee bill that reauthorizes FDA programs, and senators are currently in negotiations with the House of Representatives. The Natural Products Association opposes all of the dietary supplement provisions.
Because dietary pills, teas, and other supplements are regulated as food products, manufacturers can’t advertise them as treatments or cures for health issues. But they can make claims about how the supplements affect the body. So someone who wants to lose weight or get their diabetes under control might reach for a bottle of white mulberry leaf extract because some supplement makers advertise it as a natural remedy that can lower blood sugar levels and promote weight loss.
Those kinds of claims are appealing to Americans and have been especially potent during the pandemic, as people sought to boost their immune systems and fend off COVID-19, said Debbie Petitpain, a registered dietitian nutritionist and a spokesperson for the Academy of Nutrition and Dietetics.
But dietary supplements can be dangerous and don’t affect everyone the same way. Mixing supplements and prescription medicines can compound the problem, according to the FDA.
“I think a lot of people are thinking, ‘Oh, it’s a plant.’ Or, ‘Oh, it’s just a vitamin. Certainly, that means that it’s not going to hurt me,’ ” Ms. Petitpain said. “But there’s always a risk for taking anything.”
It’s not clear why Lori McClintock was taking white mulberry leaf. Friends and family who gathered for her funeral described a vibrant, happy woman who loved her family and her work and already had wrapped Christmas presents under the tree in mid-December. She was planning to buy a recreational vehicle with her husband in retirement.
“We grieve the loss because of all the things she was looking forward to doing and all the years yet ahead,” Tom McClintock told mourners. “And we grieve for something else, because we’ve all lost a genuinely good person in our lives.”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Long COVID mimics other postviral conditions
When Jaime Seltzer first heard about a new virus that was spreading globally early in 2020, she was on full alert. As an advocate for the post-viral condition known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), she worried about a new wave of people having long-term disabilities.
“The hair on my arms stood on end,” said Ms. Seltzer, director of scientific and medical outreach at the advocacy group MEAction and a consultant researcher at Stanford University.
Ms. Seltzer, who has had ME/CFS herself, said she wondered.
Sure enough, later in 2020, reports began emerging about people with extreme fatigue, postexertion crashes, brain fog, unrefreshing sleep, and dizziness when standing up months after a bout with the then-new viral illness. Those same symptoms had been designated as “core criteria” of ME/CFS by the National Academy of Medicine in a 2015 report.
Now, advocates like Ms. Seltzer are hoping the research and medical communities will give ME/CFS and other postviral illnesses the same attention they have increasingly focused on long COVID.
The emergence of long COVID was no surprise to researchers who study ME/CFS, because the same set of symptoms has arisen after many other viruses.
“This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” said David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital in Boston, who studies people with both diagnoses.
The actual numbers are hard to determine, since many people who meet ME/CFS criteria aren’t formally diagnosed. But a combined analysis of data from several studies published in March found that about one in three people had fatigue and about one in five reported having a hard time with thinking and memory 12 or more weeks after they had COVID-19.
According to some estimates, about half of people with long COVID will meet the criteria for ME/CFS, whether they’re given that specific diagnosis or not.
Other conditions that often exist with ME/CFS are also being seen in people with long COVID, including postural orthostatic tachycardia syndrome, which causes people to feel dizzy when they stand, along with other symptoms; other problems with the autonomic nervous system, which controls body systems such as heart rate, blood pressure, and digestion, known together as dysautonomia; and a condition related to allergies called mast cell activation disorder.
Post–acute infection syndromes have been linked to a long list of viruses, including Ebola, the 2003-2004 SARS virus, and Epstein-Barr – the virus most commonly associated with ME/CFS.
The problem in clinical medicine is that once an infection has cleared, the teaching has been that the person should no longer feel sick, said Nancy G. Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Miami. “I was taught that there has to be an antigen [such as a viral protein] in the system to drive the immune system to make it create sickness, and the immune system should shut off when it’s done,” she said.
Thus, if virus is gone and other routine lab tests come up negative, doctors often deem the person’s reported symptoms to be psychological, which can upset patients, Anthony Komaroff, MD, of Brigham and Women’s Hospital in Boston, wrote in July 2021.
Only recently have doctors started to appreciate the idea that the immune system may be overreacting long term, Dr. Klimas said.
Now, long COVID appears to be speeding up that recognition. Dr. Systrom said he has “absolutely” seen a change in attitude among fellow doctors who had been skeptical of ME/CFS as a “real” illness because there’s no test for it.
“I’m very keenly aware of a large group of health care professionals who really had not bought into the concept of ME/CFS as a real disease who have had an epiphany of sorts with long COVID and now, in a backwards way, have applied that same thinking to their very same patients with ME/CFS,” he said.
Science showing ‘frighteningly similar’ symptoms
Dr. Systrom has spent several years researching how ME/CFS patients cannot tolerate exercise and now is doing similar studies in people with long COVID. “Several months into the pandemic, we began receiving reports of patients who had survived COVID and maybe even had a relatively mild disease ... and as the summer of 2020 moved into the fall, it became apparent that there was a subset of patients who for all the world appeared to meet ME/CFS clinical criteria,” he said.
Using bicycle exercise tests on long COVID patients with catheters placed in their veins, Dr. Systrom and associates have shown a lack of exercise capacity that isn’t caused by heart or lung disease but instead is related to abnormal nerves and blood vessels, just as they’d shown previously in ME/CFS patient.
Avindra Nath, MD, senior investigator and clinical director of intramural research at the National Institute of Neurological Disorders and Stroke, Bethesda, Md., was doing a deep-dive scientific study on ME/CFS when the COVID-19 pandemic hit. Since then, he›s begun another study using the same protocol and sophisticated laboratory measurement to evaluate people with long COVID.
“As terrible as [long COVID] is, it’s kind of a blessing in disguise for ME/CFS because there’s just so much overlap between the two and they could very well be in many ways one in the same thing. The problem with studying ME/CFS is oftentimes you didn’t know what the trigger was. You see patients many years later, then try to backtrack and find out what happened,” said Dr. Nath, a neuroimmunologist.
With long COVID, on the other hand, “we know when they got infected and when their symptoms actually started, so it becomes much more uniform. ... It gives us an opportunity to maybe solve certain things in a much more well-defined population and try to find answers.”
Advocacy groups want to see more.
In February 2021, Solve M.E. launched the Long COVID Alliance, made up of several organizations, companies, and people with a goal to influence policy and speed up research into a range of postviral illnesses.
Solve M.E. has also pushed for inclusion of language regarding ME/CFS and related conditions into congressional bills addressing long COVID, including those that call for funding of research and clinical care.
“On the political front, we’ve really capitalized on a moment in time in which we have the spotlight,” said Emily Taylor, vice president of advocacy and engagement for Solve M.E.
“One of the hardest parts about ME/CFS is how to show that it’s real when it’s invisible. Most people agree that COVID is real and therefore if somebody gets ME/CFS after COVID, it’s real,” she said.
The advocacy groups are now pushing for non-COVID postinfection illnesses to be included in efforts aimed at helping people with long COVID, with mixed results. For example, the RECOVER Initiative, established in February 2021 with $1.5 billion in funding from Congress to the National Institutes of Health, is specifically for studying long COVID and does not fund research into other postinfection illnesses, although representatives from the ME/CFS community are advisers.
Language addressing ME/CFS and other postinfectious chronic illnesses has been included in several long COVID bills now pending in Congress, including the Care for Long COVID Act in the Senate and its companion COVID-19 Long Haulers Act in the House. “Our goal is to push for passage of a long COVID bill by the end of the year,” Ms. Taylor said.
A version of this article first appeared on WebMD.com.
When Jaime Seltzer first heard about a new virus that was spreading globally early in 2020, she was on full alert. As an advocate for the post-viral condition known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), she worried about a new wave of people having long-term disabilities.
“The hair on my arms stood on end,” said Ms. Seltzer, director of scientific and medical outreach at the advocacy group MEAction and a consultant researcher at Stanford University.
Ms. Seltzer, who has had ME/CFS herself, said she wondered.
Sure enough, later in 2020, reports began emerging about people with extreme fatigue, postexertion crashes, brain fog, unrefreshing sleep, and dizziness when standing up months after a bout with the then-new viral illness. Those same symptoms had been designated as “core criteria” of ME/CFS by the National Academy of Medicine in a 2015 report.
Now, advocates like Ms. Seltzer are hoping the research and medical communities will give ME/CFS and other postviral illnesses the same attention they have increasingly focused on long COVID.
The emergence of long COVID was no surprise to researchers who study ME/CFS, because the same set of symptoms has arisen after many other viruses.
“This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” said David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital in Boston, who studies people with both diagnoses.
The actual numbers are hard to determine, since many people who meet ME/CFS criteria aren’t formally diagnosed. But a combined analysis of data from several studies published in March found that about one in three people had fatigue and about one in five reported having a hard time with thinking and memory 12 or more weeks after they had COVID-19.
According to some estimates, about half of people with long COVID will meet the criteria for ME/CFS, whether they’re given that specific diagnosis or not.
Other conditions that often exist with ME/CFS are also being seen in people with long COVID, including postural orthostatic tachycardia syndrome, which causes people to feel dizzy when they stand, along with other symptoms; other problems with the autonomic nervous system, which controls body systems such as heart rate, blood pressure, and digestion, known together as dysautonomia; and a condition related to allergies called mast cell activation disorder.
Post–acute infection syndromes have been linked to a long list of viruses, including Ebola, the 2003-2004 SARS virus, and Epstein-Barr – the virus most commonly associated with ME/CFS.
The problem in clinical medicine is that once an infection has cleared, the teaching has been that the person should no longer feel sick, said Nancy G. Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Miami. “I was taught that there has to be an antigen [such as a viral protein] in the system to drive the immune system to make it create sickness, and the immune system should shut off when it’s done,” she said.
Thus, if virus is gone and other routine lab tests come up negative, doctors often deem the person’s reported symptoms to be psychological, which can upset patients, Anthony Komaroff, MD, of Brigham and Women’s Hospital in Boston, wrote in July 2021.
Only recently have doctors started to appreciate the idea that the immune system may be overreacting long term, Dr. Klimas said.
Now, long COVID appears to be speeding up that recognition. Dr. Systrom said he has “absolutely” seen a change in attitude among fellow doctors who had been skeptical of ME/CFS as a “real” illness because there’s no test for it.
“I’m very keenly aware of a large group of health care professionals who really had not bought into the concept of ME/CFS as a real disease who have had an epiphany of sorts with long COVID and now, in a backwards way, have applied that same thinking to their very same patients with ME/CFS,” he said.
Science showing ‘frighteningly similar’ symptoms
Dr. Systrom has spent several years researching how ME/CFS patients cannot tolerate exercise and now is doing similar studies in people with long COVID. “Several months into the pandemic, we began receiving reports of patients who had survived COVID and maybe even had a relatively mild disease ... and as the summer of 2020 moved into the fall, it became apparent that there was a subset of patients who for all the world appeared to meet ME/CFS clinical criteria,” he said.
Using bicycle exercise tests on long COVID patients with catheters placed in their veins, Dr. Systrom and associates have shown a lack of exercise capacity that isn’t caused by heart or lung disease but instead is related to abnormal nerves and blood vessels, just as they’d shown previously in ME/CFS patient.
Avindra Nath, MD, senior investigator and clinical director of intramural research at the National Institute of Neurological Disorders and Stroke, Bethesda, Md., was doing a deep-dive scientific study on ME/CFS when the COVID-19 pandemic hit. Since then, he›s begun another study using the same protocol and sophisticated laboratory measurement to evaluate people with long COVID.
“As terrible as [long COVID] is, it’s kind of a blessing in disguise for ME/CFS because there’s just so much overlap between the two and they could very well be in many ways one in the same thing. The problem with studying ME/CFS is oftentimes you didn’t know what the trigger was. You see patients many years later, then try to backtrack and find out what happened,” said Dr. Nath, a neuroimmunologist.
With long COVID, on the other hand, “we know when they got infected and when their symptoms actually started, so it becomes much more uniform. ... It gives us an opportunity to maybe solve certain things in a much more well-defined population and try to find answers.”
Advocacy groups want to see more.
In February 2021, Solve M.E. launched the Long COVID Alliance, made up of several organizations, companies, and people with a goal to influence policy and speed up research into a range of postviral illnesses.
Solve M.E. has also pushed for inclusion of language regarding ME/CFS and related conditions into congressional bills addressing long COVID, including those that call for funding of research and clinical care.
“On the political front, we’ve really capitalized on a moment in time in which we have the spotlight,” said Emily Taylor, vice president of advocacy and engagement for Solve M.E.
“One of the hardest parts about ME/CFS is how to show that it’s real when it’s invisible. Most people agree that COVID is real and therefore if somebody gets ME/CFS after COVID, it’s real,” she said.
The advocacy groups are now pushing for non-COVID postinfection illnesses to be included in efforts aimed at helping people with long COVID, with mixed results. For example, the RECOVER Initiative, established in February 2021 with $1.5 billion in funding from Congress to the National Institutes of Health, is specifically for studying long COVID and does not fund research into other postinfection illnesses, although representatives from the ME/CFS community are advisers.
Language addressing ME/CFS and other postinfectious chronic illnesses has been included in several long COVID bills now pending in Congress, including the Care for Long COVID Act in the Senate and its companion COVID-19 Long Haulers Act in the House. “Our goal is to push for passage of a long COVID bill by the end of the year,” Ms. Taylor said.
A version of this article first appeared on WebMD.com.
When Jaime Seltzer first heard about a new virus that was spreading globally early in 2020, she was on full alert. As an advocate for the post-viral condition known as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), she worried about a new wave of people having long-term disabilities.
“The hair on my arms stood on end,” said Ms. Seltzer, director of scientific and medical outreach at the advocacy group MEAction and a consultant researcher at Stanford University.
Ms. Seltzer, who has had ME/CFS herself, said she wondered.
Sure enough, later in 2020, reports began emerging about people with extreme fatigue, postexertion crashes, brain fog, unrefreshing sleep, and dizziness when standing up months after a bout with the then-new viral illness. Those same symptoms had been designated as “core criteria” of ME/CFS by the National Academy of Medicine in a 2015 report.
Now, advocates like Ms. Seltzer are hoping the research and medical communities will give ME/CFS and other postviral illnesses the same attention they have increasingly focused on long COVID.
The emergence of long COVID was no surprise to researchers who study ME/CFS, because the same set of symptoms has arisen after many other viruses.
“This for all the world looks like ME/CFS. We think they are frighteningly similar, if not identical,” said David M. Systrom, MD, a pulmonary and critical care medicine specialist at Brigham and Women’s Hospital in Boston, who studies people with both diagnoses.
The actual numbers are hard to determine, since many people who meet ME/CFS criteria aren’t formally diagnosed. But a combined analysis of data from several studies published in March found that about one in three people had fatigue and about one in five reported having a hard time with thinking and memory 12 or more weeks after they had COVID-19.
According to some estimates, about half of people with long COVID will meet the criteria for ME/CFS, whether they’re given that specific diagnosis or not.
Other conditions that often exist with ME/CFS are also being seen in people with long COVID, including postural orthostatic tachycardia syndrome, which causes people to feel dizzy when they stand, along with other symptoms; other problems with the autonomic nervous system, which controls body systems such as heart rate, blood pressure, and digestion, known together as dysautonomia; and a condition related to allergies called mast cell activation disorder.
Post–acute infection syndromes have been linked to a long list of viruses, including Ebola, the 2003-2004 SARS virus, and Epstein-Barr – the virus most commonly associated with ME/CFS.
The problem in clinical medicine is that once an infection has cleared, the teaching has been that the person should no longer feel sick, said Nancy G. Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Miami. “I was taught that there has to be an antigen [such as a viral protein] in the system to drive the immune system to make it create sickness, and the immune system should shut off when it’s done,” she said.
Thus, if virus is gone and other routine lab tests come up negative, doctors often deem the person’s reported symptoms to be psychological, which can upset patients, Anthony Komaroff, MD, of Brigham and Women’s Hospital in Boston, wrote in July 2021.
Only recently have doctors started to appreciate the idea that the immune system may be overreacting long term, Dr. Klimas said.
Now, long COVID appears to be speeding up that recognition. Dr. Systrom said he has “absolutely” seen a change in attitude among fellow doctors who had been skeptical of ME/CFS as a “real” illness because there’s no test for it.
“I’m very keenly aware of a large group of health care professionals who really had not bought into the concept of ME/CFS as a real disease who have had an epiphany of sorts with long COVID and now, in a backwards way, have applied that same thinking to their very same patients with ME/CFS,” he said.
Science showing ‘frighteningly similar’ symptoms
Dr. Systrom has spent several years researching how ME/CFS patients cannot tolerate exercise and now is doing similar studies in people with long COVID. “Several months into the pandemic, we began receiving reports of patients who had survived COVID and maybe even had a relatively mild disease ... and as the summer of 2020 moved into the fall, it became apparent that there was a subset of patients who for all the world appeared to meet ME/CFS clinical criteria,” he said.
Using bicycle exercise tests on long COVID patients with catheters placed in their veins, Dr. Systrom and associates have shown a lack of exercise capacity that isn’t caused by heart or lung disease but instead is related to abnormal nerves and blood vessels, just as they’d shown previously in ME/CFS patient.
Avindra Nath, MD, senior investigator and clinical director of intramural research at the National Institute of Neurological Disorders and Stroke, Bethesda, Md., was doing a deep-dive scientific study on ME/CFS when the COVID-19 pandemic hit. Since then, he›s begun another study using the same protocol and sophisticated laboratory measurement to evaluate people with long COVID.
“As terrible as [long COVID] is, it’s kind of a blessing in disguise for ME/CFS because there’s just so much overlap between the two and they could very well be in many ways one in the same thing. The problem with studying ME/CFS is oftentimes you didn’t know what the trigger was. You see patients many years later, then try to backtrack and find out what happened,” said Dr. Nath, a neuroimmunologist.
With long COVID, on the other hand, “we know when they got infected and when their symptoms actually started, so it becomes much more uniform. ... It gives us an opportunity to maybe solve certain things in a much more well-defined population and try to find answers.”
Advocacy groups want to see more.
In February 2021, Solve M.E. launched the Long COVID Alliance, made up of several organizations, companies, and people with a goal to influence policy and speed up research into a range of postviral illnesses.
Solve M.E. has also pushed for inclusion of language regarding ME/CFS and related conditions into congressional bills addressing long COVID, including those that call for funding of research and clinical care.
“On the political front, we’ve really capitalized on a moment in time in which we have the spotlight,” said Emily Taylor, vice president of advocacy and engagement for Solve M.E.
“One of the hardest parts about ME/CFS is how to show that it’s real when it’s invisible. Most people agree that COVID is real and therefore if somebody gets ME/CFS after COVID, it’s real,” she said.
The advocacy groups are now pushing for non-COVID postinfection illnesses to be included in efforts aimed at helping people with long COVID, with mixed results. For example, the RECOVER Initiative, established in February 2021 with $1.5 billion in funding from Congress to the National Institutes of Health, is specifically for studying long COVID and does not fund research into other postinfection illnesses, although representatives from the ME/CFS community are advisers.
Language addressing ME/CFS and other postinfectious chronic illnesses has been included in several long COVID bills now pending in Congress, including the Care for Long COVID Act in the Senate and its companion COVID-19 Long Haulers Act in the House. “Our goal is to push for passage of a long COVID bill by the end of the year,” Ms. Taylor said.
A version of this article first appeared on WebMD.com.
New international consensus document on treating OSA
The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has issued a new international consensus document (ICD) on obstructive sleep apnea (OSA). The objective is to improve the diagnosis and treatment of one of the most prevalent sleep disorders.
It provides a series of clinical guidelines to help health care professionals make the best decisions for adult patients with OSA. Notably, the authors propose changing the name from sleep apnea syndrome. In recommending the term OSA, they reintroduce the term “obstructive” – to differentiate the disorder from central sleep apnea – and remove the outdated word “syndrome.”
“The definition has also been changed, as it was a bit vague and difficult to understand. And there are significant changes to the treatment and to the diagnostic algorithms – one for primary care and another for sleep units,” Olga Mediano, MD, said in an interview. She is a SEPAR pulmonologist, first author of the ICD, and the coordinator of SEPAR 2022 Year of Intermediate Respiratory Care Units.
Diagnosis in primary care
The ICD indicates that all levels of care must be involved in the management of OSA, a condition in which complete or partial upper airway blockage occurs during sleep, causing the individual to stop breathing for a few seconds. These pauses, which produce hypoxia and sleep fragmentation, increase the risk of workplace and traffic accidents, affect cardiovascular health, and contribute to uncontrolled or resistant hypertension.
The recommendations in the ICD aim at increasing the role of primary care physicians so as to reduce underdiagnosis of OSA in primary care. “The vast majority of patients with OSA haven’t been diagnosed. In fact, those whom we have diagnosed are the patients with the most severe cases – in other words, patients who present with the most symptoms,” said Dr. Mediano. She explained that many patients with OSA don’t consider it a medical condition, so they do not go to the doctor.
“The other big problem is that, before, there was a preconceived notion of the typical OSA patient: A middle-aged obese man who’s fallen asleep in the waiting room. However, there are many other profiles: thin build, women. ... Sleep has a heterogeneous profile, and all profiles need to be known,” said Dr. Mediano. The difficulties in carrying out a sleep study with the various patients are an added problem that the new consensus document also seeks to resolve. “The step we’ve taken is to involve the primary care physician in super-simplified studies to reach more people,” she said. For this, the primary care site must work in coordination with a sleep unit.
“In the super-simplified study, the patient is given a machine to use at home; they hook themselves up to it when they go to sleep. This machine records the number of apnea episodes the patient experiences during the night, as well as the oxygen level. The next day, the patient returns the machine. The data are downloaded to a computer. The software analyzes the breathing pauses that the patient had during the night and automatically gives a series of values that, if very pronounced, as the document indicates, would lead to a diagnosis of OSA. Once diagnosed by a primary care physician, the patient is referred to a sleep unit where treatment can then be assessed,” explained Dr. Mediano.
Different treatments
The new ICD’s approach incorporates therapeutic alternatives as well. Until now, many consensus documents and clinical guidelines have focused on continuous positive airway pressure therapy, in which a machine delivers continuous airflow to help keep the patient’s airway open and unobstructed during sleep. Some guidelines recommend its use, and others do not. “However, in this new document, management of the patient is much more multidisciplinary. What changes, with respect to the treatment, is the philosophy. It’s not one single type of treatment; rather, other therapeutic options are kept in mind,” said Dr. Mediano.
First, treatment of reversible causes of OSA must be offered. The conditions that lead to OSA and that can be reversed are addressed. These include overweight and obesity; heavy drinking; tonsillar hypertrophy, or severe dental or facial alterations, for which surgery can be considered; and gastroesophageal reflux or hypothyroidism, both of which can be treated. “For example, the leading cause of sleep apnea is obesity. If we can get the patient to lose weight, that can end up making the OSA go away. What does the document say? Well, you have to try to implement intensive strategies regarding diet, exercise, etc. And if that’s not enough, you need to consider using drugs or even bariatric surgery,” said Dr. Mediano.
“If there’s no one definitive treatment, we highly recommend that all patients implement hygienic-dietary measures and then assess all the therapeutic options. In some cases, several can be in place at the same time,” she said. Various medical specialists can play a role in the treatment of OSA, said Dr. Mediano. They include otolaryngologists, maxillofacial surgeons, dentists, cardiologists, and neurophysiologists, to mention a few.
A website has been created to explain the ICD. There, visitors will be able to find the most up-to-date version of the ICD as well as related information, news, and materials.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has issued a new international consensus document (ICD) on obstructive sleep apnea (OSA). The objective is to improve the diagnosis and treatment of one of the most prevalent sleep disorders.
It provides a series of clinical guidelines to help health care professionals make the best decisions for adult patients with OSA. Notably, the authors propose changing the name from sleep apnea syndrome. In recommending the term OSA, they reintroduce the term “obstructive” – to differentiate the disorder from central sleep apnea – and remove the outdated word “syndrome.”
“The definition has also been changed, as it was a bit vague and difficult to understand. And there are significant changes to the treatment and to the diagnostic algorithms – one for primary care and another for sleep units,” Olga Mediano, MD, said in an interview. She is a SEPAR pulmonologist, first author of the ICD, and the coordinator of SEPAR 2022 Year of Intermediate Respiratory Care Units.
Diagnosis in primary care
The ICD indicates that all levels of care must be involved in the management of OSA, a condition in which complete or partial upper airway blockage occurs during sleep, causing the individual to stop breathing for a few seconds. These pauses, which produce hypoxia and sleep fragmentation, increase the risk of workplace and traffic accidents, affect cardiovascular health, and contribute to uncontrolled or resistant hypertension.
The recommendations in the ICD aim at increasing the role of primary care physicians so as to reduce underdiagnosis of OSA in primary care. “The vast majority of patients with OSA haven’t been diagnosed. In fact, those whom we have diagnosed are the patients with the most severe cases – in other words, patients who present with the most symptoms,” said Dr. Mediano. She explained that many patients with OSA don’t consider it a medical condition, so they do not go to the doctor.
“The other big problem is that, before, there was a preconceived notion of the typical OSA patient: A middle-aged obese man who’s fallen asleep in the waiting room. However, there are many other profiles: thin build, women. ... Sleep has a heterogeneous profile, and all profiles need to be known,” said Dr. Mediano. The difficulties in carrying out a sleep study with the various patients are an added problem that the new consensus document also seeks to resolve. “The step we’ve taken is to involve the primary care physician in super-simplified studies to reach more people,” she said. For this, the primary care site must work in coordination with a sleep unit.
“In the super-simplified study, the patient is given a machine to use at home; they hook themselves up to it when they go to sleep. This machine records the number of apnea episodes the patient experiences during the night, as well as the oxygen level. The next day, the patient returns the machine. The data are downloaded to a computer. The software analyzes the breathing pauses that the patient had during the night and automatically gives a series of values that, if very pronounced, as the document indicates, would lead to a diagnosis of OSA. Once diagnosed by a primary care physician, the patient is referred to a sleep unit where treatment can then be assessed,” explained Dr. Mediano.
Different treatments
The new ICD’s approach incorporates therapeutic alternatives as well. Until now, many consensus documents and clinical guidelines have focused on continuous positive airway pressure therapy, in which a machine delivers continuous airflow to help keep the patient’s airway open and unobstructed during sleep. Some guidelines recommend its use, and others do not. “However, in this new document, management of the patient is much more multidisciplinary. What changes, with respect to the treatment, is the philosophy. It’s not one single type of treatment; rather, other therapeutic options are kept in mind,” said Dr. Mediano.
First, treatment of reversible causes of OSA must be offered. The conditions that lead to OSA and that can be reversed are addressed. These include overweight and obesity; heavy drinking; tonsillar hypertrophy, or severe dental or facial alterations, for which surgery can be considered; and gastroesophageal reflux or hypothyroidism, both of which can be treated. “For example, the leading cause of sleep apnea is obesity. If we can get the patient to lose weight, that can end up making the OSA go away. What does the document say? Well, you have to try to implement intensive strategies regarding diet, exercise, etc. And if that’s not enough, you need to consider using drugs or even bariatric surgery,” said Dr. Mediano.
“If there’s no one definitive treatment, we highly recommend that all patients implement hygienic-dietary measures and then assess all the therapeutic options. In some cases, several can be in place at the same time,” she said. Various medical specialists can play a role in the treatment of OSA, said Dr. Mediano. They include otolaryngologists, maxillofacial surgeons, dentists, cardiologists, and neurophysiologists, to mention a few.
A website has been created to explain the ICD. There, visitors will be able to find the most up-to-date version of the ICD as well as related information, news, and materials.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
The Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has issued a new international consensus document (ICD) on obstructive sleep apnea (OSA). The objective is to improve the diagnosis and treatment of one of the most prevalent sleep disorders.
It provides a series of clinical guidelines to help health care professionals make the best decisions for adult patients with OSA. Notably, the authors propose changing the name from sleep apnea syndrome. In recommending the term OSA, they reintroduce the term “obstructive” – to differentiate the disorder from central sleep apnea – and remove the outdated word “syndrome.”
“The definition has also been changed, as it was a bit vague and difficult to understand. And there are significant changes to the treatment and to the diagnostic algorithms – one for primary care and another for sleep units,” Olga Mediano, MD, said in an interview. She is a SEPAR pulmonologist, first author of the ICD, and the coordinator of SEPAR 2022 Year of Intermediate Respiratory Care Units.
Diagnosis in primary care
The ICD indicates that all levels of care must be involved in the management of OSA, a condition in which complete or partial upper airway blockage occurs during sleep, causing the individual to stop breathing for a few seconds. These pauses, which produce hypoxia and sleep fragmentation, increase the risk of workplace and traffic accidents, affect cardiovascular health, and contribute to uncontrolled or resistant hypertension.
The recommendations in the ICD aim at increasing the role of primary care physicians so as to reduce underdiagnosis of OSA in primary care. “The vast majority of patients with OSA haven’t been diagnosed. In fact, those whom we have diagnosed are the patients with the most severe cases – in other words, patients who present with the most symptoms,” said Dr. Mediano. She explained that many patients with OSA don’t consider it a medical condition, so they do not go to the doctor.
“The other big problem is that, before, there was a preconceived notion of the typical OSA patient: A middle-aged obese man who’s fallen asleep in the waiting room. However, there are many other profiles: thin build, women. ... Sleep has a heterogeneous profile, and all profiles need to be known,” said Dr. Mediano. The difficulties in carrying out a sleep study with the various patients are an added problem that the new consensus document also seeks to resolve. “The step we’ve taken is to involve the primary care physician in super-simplified studies to reach more people,” she said. For this, the primary care site must work in coordination with a sleep unit.
“In the super-simplified study, the patient is given a machine to use at home; they hook themselves up to it when they go to sleep. This machine records the number of apnea episodes the patient experiences during the night, as well as the oxygen level. The next day, the patient returns the machine. The data are downloaded to a computer. The software analyzes the breathing pauses that the patient had during the night and automatically gives a series of values that, if very pronounced, as the document indicates, would lead to a diagnosis of OSA. Once diagnosed by a primary care physician, the patient is referred to a sleep unit where treatment can then be assessed,” explained Dr. Mediano.
Different treatments
The new ICD’s approach incorporates therapeutic alternatives as well. Until now, many consensus documents and clinical guidelines have focused on continuous positive airway pressure therapy, in which a machine delivers continuous airflow to help keep the patient’s airway open and unobstructed during sleep. Some guidelines recommend its use, and others do not. “However, in this new document, management of the patient is much more multidisciplinary. What changes, with respect to the treatment, is the philosophy. It’s not one single type of treatment; rather, other therapeutic options are kept in mind,” said Dr. Mediano.
First, treatment of reversible causes of OSA must be offered. The conditions that lead to OSA and that can be reversed are addressed. These include overweight and obesity; heavy drinking; tonsillar hypertrophy, or severe dental or facial alterations, for which surgery can be considered; and gastroesophageal reflux or hypothyroidism, both of which can be treated. “For example, the leading cause of sleep apnea is obesity. If we can get the patient to lose weight, that can end up making the OSA go away. What does the document say? Well, you have to try to implement intensive strategies regarding diet, exercise, etc. And if that’s not enough, you need to consider using drugs or even bariatric surgery,” said Dr. Mediano.
“If there’s no one definitive treatment, we highly recommend that all patients implement hygienic-dietary measures and then assess all the therapeutic options. In some cases, several can be in place at the same time,” she said. Various medical specialists can play a role in the treatment of OSA, said Dr. Mediano. They include otolaryngologists, maxillofacial surgeons, dentists, cardiologists, and neurophysiologists, to mention a few.
A website has been created to explain the ICD. There, visitors will be able to find the most up-to-date version of the ICD as well as related information, news, and materials.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
First drug therapy approved for childhood GVHD
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
Specifically, the indication is for pediatric patients with cGVHD who have already been treated with one or more lines of systemic therapy. The manufacturers have also launched a new oral suspension formulation, in addition to capsules and tablets, which were already available.
Ibrutinib is already approved for use in adults with cGVHD.
The drug is also approved for use in several blood cancers, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. All these approvals are for adult patients.
This is the first pediatric indication for the product and is “incredibly meaningful,” said Gauri Sunkersett, DO, associate medical director at AbbVie, which markets the drug together with Jansen. “As a pediatric oncologist, when my patients describe the physical pain they experience from simply hugging their parents, due to their cGVHD, the importance of researching alternative treatment options in this patient population is further validated.”
These children have already been through a lot, having been diagnosed with a leukemia or lymphoma and then undergoing chemotherapy and/or radiotherapy for a stem cell transplant. Just over half (52%-65%) of children who receive allogeneic transplants go on to develop cGVHD, in which the donor bone marrow or stem cells attack the recipient.
“Imagine going through a transplant and then being told you have a moderate to severe chronic disease that can sometimes also be life-threatening,” commented Paul A. Carpenter, MD, attending physician at Seattle Children’s Hospital. “If these children were between 1 and 12 and didn’t respond to steroid treatment, we didn’t have any rigorously studied treatment options – until now.”
The new indication was approved by the U.S. Food and Drug Administration on the basis of results from the iMAGINE trial, for which Dr. Carpenter was a principal investigator.
The phase 1/2 iMAGINE trial was an open-label, multicenter, single-arm trial conducted with 47 patients (mean age, 13 years; range, 1-19 years) with relapsed/refractory cGVHD who had received at least one prior systemic therapy. Ibrutinib was given at a dose of 420 mg orally once daily to patients aged 12 and older and at a dose of 240 mg/m2 orally once daily to patients who were younger than 12 years.
The overall response rate through week 25 was 60% (confidence interval, 95%, 44%-74%). The median duration of response was 5.3 months (95% CI, 2.8-8.8).
The safety profile was consistent with the established profile for ibrutinib. Observed adverse events in pediatric patients were consistent with those observed in adult patients with moderate to severe cGVHD, the companies noted.
The FDA noted that the most common (≥ 20%) adverse reactions, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
Full prescribing information for ibrutinib is available here.
A version of this article first appeared on Medscape.com.
Hospitalized COVID-19 patients with GI symptoms have worse outcomes
Patients with COVID-19 who experience gastrointestinal symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality, according to a new study.
About 20% of COVID-19 patients experience gastrointestinal symptoms, such as abdominal pain, diarrhea, nausea, and vomiting, which clinicians should consider when treating their hospitalized patients, wrote researchers led by Nikita Patil, MD, a hospitalist at Nash General Hospital–UNC Nash Healthcare in Rocky Mount, N.C., in Gastro Hep Advances.
“It’s important to know that certain complications are higher in people with GI symptoms,” she said in an interview. “Even without an increased risk of death, there are many problems that affect quality of life and lead to people not being able to do the things they were able to do before.”
Dr. Patil and colleagues analyzed the association of GI symptoms with adverse outcomes in 100,902 patients from the Cerner Real-World Data COVID-19 Database, which included hospital encounters and ED visits for COVID-19 between December 2019 to November 2020; the data were taken from EMRs at centers with which Cerner has a data use agreement. They also looked at factors associated with poor outcomes such as acute respiratory distress syndrome, sepsis, and ventilator requirement or oxygen dependence.
The average age of the patients was 52, and a higher proportion of patients with GI symptoms were 50 and older. Of those with GI symptoms, 54.5% were women. Overall, patients with GI symptoms were more likely to have higher Charlson Comorbidity Index scores and have comorbidities such as acute liver failure, gastroesophageal reflux disease, GI malignancy, and inflammatory bowel disease.
The research team found that COVID-19 patients with GI symptoms were more likely to have acute respiratory distress syndrome (odds ratio, 1.20; 95% confidence interval, 1.11-1.29), sepsis (OR, 1.19; 95% CI, 1.14-1.24), acute kidney injury (OR, 1.30; 95% CI, 1.24-1.36), venous thromboembolism (OR, 1.36; 95% CI, 1.22-1.52), and GI bleeding (OR 1.62; 95% CI, 1.47-1.79), as compared with COVID-19 patients without GI symptoms (P < .0001 for all comparisons). At the same time, those with GI symptoms were less likely to experience cardiomyopathy (OR, 0.87; 95% CI, 0.77-0.99; P = .027), respiratory failure (OR, 0.92; 95% CI, 0.88-0.95; P < .0001), or death (OR, 0.71; 95% CI, 0.67-0.75; P < .0001).
GI bleed was the most common GI complication, found among 2% of all patients, and was more likely in patients with GI symptoms than in those without (3.5% vs. 1.6%). Intestinal ischemia, pancreatitis, acute liver injury, and intestinal pseudo-obstruction weren’t associated with GI symptoms.
Among the 19,915 patients with GI symptoms, older age, higher Charlson Comorbidity Index scores, use of proton pump inhibitors, and use of H2 receptor antagonists were associated with higher mortality, acute respiratory distress syndrome, sepsis, and ventilator or oxygen requirement. Men with GI symptoms also had a higher risk of mortality, acute respiratory distress syndrome, and sepsis.
In particular, proton pump inhibitor use was associated with more than twice the risk of acute respiratory distress syndrome (OR, 2.19; 95% CI, 1.32-1.66; P < .0001). Similarly, H2 receptor antagonist use was associated with higher likelihood of death (OR, 1.78; 95% CI, 1.57-2.02), as well as more than three times the risk of acute respiratory distress syndrome (OR, 3.75; 95% CI, 3.29-4.28), more than twice the risk of sepsis (OR, 2.50; 95% CI, 2.28-2.73), and nearly twice the risk of ventilator or oxygen dependence (OR, 1.97; 95% CI, 1.68-2.30) (P < .0001 for all).
The findings could guide risk stratification, prognosis, and treatment decisions in COVID-19 patients with GI symptoms, as well as inform future research focused on risk mitigation and improvement of COVID-19 outcomes, Dr. Patil said.
“The protocols for COVID-19 treatment have changed over the past 2 years with blood thinners and steroids,” she said. “Although we likely can’t avoid anti-reflux medicines entirely, it’s something we need to be cognizant of and look out for in our hospitalized patients.”
One study limitation was its inclusion of only inpatient or ED encounters and, therefore, omission of those treated at home; this confers bias toward those with more aggressive disease, according to the authors.
The authors reported no grant support or funding sources for this study. One author declared grant support and consultant fees from several companies, including some medical and pharmaceutical companies, which were unrelated to this research. Dr. Patil reported no disclosures.
This article was updated Aug. 26, 2022.
Patients with COVID-19 who experience gastrointestinal symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality, according to a new study.
About 20% of COVID-19 patients experience gastrointestinal symptoms, such as abdominal pain, diarrhea, nausea, and vomiting, which clinicians should consider when treating their hospitalized patients, wrote researchers led by Nikita Patil, MD, a hospitalist at Nash General Hospital–UNC Nash Healthcare in Rocky Mount, N.C., in Gastro Hep Advances.
“It’s important to know that certain complications are higher in people with GI symptoms,” she said in an interview. “Even without an increased risk of death, there are many problems that affect quality of life and lead to people not being able to do the things they were able to do before.”
Dr. Patil and colleagues analyzed the association of GI symptoms with adverse outcomes in 100,902 patients from the Cerner Real-World Data COVID-19 Database, which included hospital encounters and ED visits for COVID-19 between December 2019 to November 2020; the data were taken from EMRs at centers with which Cerner has a data use agreement. They also looked at factors associated with poor outcomes such as acute respiratory distress syndrome, sepsis, and ventilator requirement or oxygen dependence.
The average age of the patients was 52, and a higher proportion of patients with GI symptoms were 50 and older. Of those with GI symptoms, 54.5% were women. Overall, patients with GI symptoms were more likely to have higher Charlson Comorbidity Index scores and have comorbidities such as acute liver failure, gastroesophageal reflux disease, GI malignancy, and inflammatory bowel disease.
The research team found that COVID-19 patients with GI symptoms were more likely to have acute respiratory distress syndrome (odds ratio, 1.20; 95% confidence interval, 1.11-1.29), sepsis (OR, 1.19; 95% CI, 1.14-1.24), acute kidney injury (OR, 1.30; 95% CI, 1.24-1.36), venous thromboembolism (OR, 1.36; 95% CI, 1.22-1.52), and GI bleeding (OR 1.62; 95% CI, 1.47-1.79), as compared with COVID-19 patients without GI symptoms (P < .0001 for all comparisons). At the same time, those with GI symptoms were less likely to experience cardiomyopathy (OR, 0.87; 95% CI, 0.77-0.99; P = .027), respiratory failure (OR, 0.92; 95% CI, 0.88-0.95; P < .0001), or death (OR, 0.71; 95% CI, 0.67-0.75; P < .0001).
GI bleed was the most common GI complication, found among 2% of all patients, and was more likely in patients with GI symptoms than in those without (3.5% vs. 1.6%). Intestinal ischemia, pancreatitis, acute liver injury, and intestinal pseudo-obstruction weren’t associated with GI symptoms.
Among the 19,915 patients with GI symptoms, older age, higher Charlson Comorbidity Index scores, use of proton pump inhibitors, and use of H2 receptor antagonists were associated with higher mortality, acute respiratory distress syndrome, sepsis, and ventilator or oxygen requirement. Men with GI symptoms also had a higher risk of mortality, acute respiratory distress syndrome, and sepsis.
In particular, proton pump inhibitor use was associated with more than twice the risk of acute respiratory distress syndrome (OR, 2.19; 95% CI, 1.32-1.66; P < .0001). Similarly, H2 receptor antagonist use was associated with higher likelihood of death (OR, 1.78; 95% CI, 1.57-2.02), as well as more than three times the risk of acute respiratory distress syndrome (OR, 3.75; 95% CI, 3.29-4.28), more than twice the risk of sepsis (OR, 2.50; 95% CI, 2.28-2.73), and nearly twice the risk of ventilator or oxygen dependence (OR, 1.97; 95% CI, 1.68-2.30) (P < .0001 for all).
The findings could guide risk stratification, prognosis, and treatment decisions in COVID-19 patients with GI symptoms, as well as inform future research focused on risk mitigation and improvement of COVID-19 outcomes, Dr. Patil said.
“The protocols for COVID-19 treatment have changed over the past 2 years with blood thinners and steroids,” she said. “Although we likely can’t avoid anti-reflux medicines entirely, it’s something we need to be cognizant of and look out for in our hospitalized patients.”
One study limitation was its inclusion of only inpatient or ED encounters and, therefore, omission of those treated at home; this confers bias toward those with more aggressive disease, according to the authors.
The authors reported no grant support or funding sources for this study. One author declared grant support and consultant fees from several companies, including some medical and pharmaceutical companies, which were unrelated to this research. Dr. Patil reported no disclosures.
This article was updated Aug. 26, 2022.
Patients with COVID-19 who experience gastrointestinal symptoms have overall worse in-hospital complications but less cardiomyopathy and mortality, according to a new study.
About 20% of COVID-19 patients experience gastrointestinal symptoms, such as abdominal pain, diarrhea, nausea, and vomiting, which clinicians should consider when treating their hospitalized patients, wrote researchers led by Nikita Patil, MD, a hospitalist at Nash General Hospital–UNC Nash Healthcare in Rocky Mount, N.C., in Gastro Hep Advances.
“It’s important to know that certain complications are higher in people with GI symptoms,” she said in an interview. “Even without an increased risk of death, there are many problems that affect quality of life and lead to people not being able to do the things they were able to do before.”
Dr. Patil and colleagues analyzed the association of GI symptoms with adverse outcomes in 100,902 patients from the Cerner Real-World Data COVID-19 Database, which included hospital encounters and ED visits for COVID-19 between December 2019 to November 2020; the data were taken from EMRs at centers with which Cerner has a data use agreement. They also looked at factors associated with poor outcomes such as acute respiratory distress syndrome, sepsis, and ventilator requirement or oxygen dependence.
The average age of the patients was 52, and a higher proportion of patients with GI symptoms were 50 and older. Of those with GI symptoms, 54.5% were women. Overall, patients with GI symptoms were more likely to have higher Charlson Comorbidity Index scores and have comorbidities such as acute liver failure, gastroesophageal reflux disease, GI malignancy, and inflammatory bowel disease.
The research team found that COVID-19 patients with GI symptoms were more likely to have acute respiratory distress syndrome (odds ratio, 1.20; 95% confidence interval, 1.11-1.29), sepsis (OR, 1.19; 95% CI, 1.14-1.24), acute kidney injury (OR, 1.30; 95% CI, 1.24-1.36), venous thromboembolism (OR, 1.36; 95% CI, 1.22-1.52), and GI bleeding (OR 1.62; 95% CI, 1.47-1.79), as compared with COVID-19 patients without GI symptoms (P < .0001 for all comparisons). At the same time, those with GI symptoms were less likely to experience cardiomyopathy (OR, 0.87; 95% CI, 0.77-0.99; P = .027), respiratory failure (OR, 0.92; 95% CI, 0.88-0.95; P < .0001), or death (OR, 0.71; 95% CI, 0.67-0.75; P < .0001).
GI bleed was the most common GI complication, found among 2% of all patients, and was more likely in patients with GI symptoms than in those without (3.5% vs. 1.6%). Intestinal ischemia, pancreatitis, acute liver injury, and intestinal pseudo-obstruction weren’t associated with GI symptoms.
Among the 19,915 patients with GI symptoms, older age, higher Charlson Comorbidity Index scores, use of proton pump inhibitors, and use of H2 receptor antagonists were associated with higher mortality, acute respiratory distress syndrome, sepsis, and ventilator or oxygen requirement. Men with GI symptoms also had a higher risk of mortality, acute respiratory distress syndrome, and sepsis.
In particular, proton pump inhibitor use was associated with more than twice the risk of acute respiratory distress syndrome (OR, 2.19; 95% CI, 1.32-1.66; P < .0001). Similarly, H2 receptor antagonist use was associated with higher likelihood of death (OR, 1.78; 95% CI, 1.57-2.02), as well as more than three times the risk of acute respiratory distress syndrome (OR, 3.75; 95% CI, 3.29-4.28), more than twice the risk of sepsis (OR, 2.50; 95% CI, 2.28-2.73), and nearly twice the risk of ventilator or oxygen dependence (OR, 1.97; 95% CI, 1.68-2.30) (P < .0001 for all).
The findings could guide risk stratification, prognosis, and treatment decisions in COVID-19 patients with GI symptoms, as well as inform future research focused on risk mitigation and improvement of COVID-19 outcomes, Dr. Patil said.
“The protocols for COVID-19 treatment have changed over the past 2 years with blood thinners and steroids,” she said. “Although we likely can’t avoid anti-reflux medicines entirely, it’s something we need to be cognizant of and look out for in our hospitalized patients.”
One study limitation was its inclusion of only inpatient or ED encounters and, therefore, omission of those treated at home; this confers bias toward those with more aggressive disease, according to the authors.
The authors reported no grant support or funding sources for this study. One author declared grant support and consultant fees from several companies, including some medical and pharmaceutical companies, which were unrelated to this research. Dr. Patil reported no disclosures.
This article was updated Aug. 26, 2022.
FROM GASTRO HEP ADVANCES
Early menopause linked with increased risk of heart problems
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.
SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.
“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”
Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
A national population
Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.
The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.
Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.
The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
Reproductive history
The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.
The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.
Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”
A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.
Monkeypox in children and women remains rare, CDC data show
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
Monkeypox cases in the United States continue to be rare in children younger than 15, women, and in individuals older than 60, according to new data released by the Centers for Disease Control and Prevention. Men aged 26-40 make up the highest proportion of cases.
The age distribution of cases is similar to those of sexually transmitted infections, said Monica Gandhi, MD, MPH, associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco. It is most common in younger to middle-aged age groups, and less common in children and older individuals. As of Aug. 21, only 17 children younger than 15 have been diagnosed with monkeypox in the United States, and women make up fewer than 1.5% of cases.
“This data should be very reassuring to parents and to children going to back to school,” Dr. Gandhi said in an interview. After 3 months of monitoring the virus, the data suggest that monkeypox is primarily spreading in networks of men who have sex with men (MSM) through sexual activity, “and that isn’t something we worry about with school-spread illness.”
In addition to the reassuring data about children and monkeypox, the CDC released laboratory testing data, a behavioral survey of MSM, patient data on the antiviral medication tecovirimat (TPOXX), and other case demographics and symptoms.
Though the number of positive monkeypox tests have continued to rise, the test-positivity rates have declined over the past month, data show. Since July 16, the positivity rate has dipped from 54% to 23%. This trend is likely because of an increase in testing availability, said Randolph Hubach, PhD, MPH, the director of the Sexual Health Research Lab at Purdue University, West Lafayette, Ind.
“We also saw this with COVID early on with testing: it was really limited to folks who were symptomatic,” he said in an interview . “As testing ramped up in accessibility, you had a lot more negative results, but because testing was more widely available, you were able to capture more positive results.”
The data also show that case numbers continue to grow in the United States, whereas in other countries that identified cases before the United States – Spain, the United Kingdom, and France, for example – cases have been leveling off, noted Dr. Gandhi.
The CDC also shared responses from a survey of gay, bisexual, and other MSM conducted from Aug. 5-15, about how they have changed their sexual behaviors in response to the monkeypox outbreak. Half of respondents reported reduced one-time sexual encounters, 49% reported reducing sex with partners met on dating apps or at sex venues, and 48% reported reducing their number of sex partners. These responses are “heartening to see,” Dr. Gandhi said, and shows that individuals are taking proactive steps to reduce their potential exposure risk to monkeypox.
More detailed demographic data showed that Black, Hispanic, or Latinx individuals make up an increasing proportion of cases in the United States. In May, 71% of people with reported monkeypox infection were White and 29% were Black. For the week of August 8-14, about a third (31%) of monkeypox cases were in White people, 32% were in Hispanic or Latinx people, and 33% were in Black people.
The most common symptoms of monkeypox were rash (98.6%), malaise (72.7%), fever (72.1%), and chills (68.9%). Rectal pain was reported in 43.9% of patients, and 25% had rectal bleeding.
The CDC also released information on 288 patients with monkeypox treated with TPOXX under compassionate use. The median age of patients was 37 and 98.9% were male. About 40% of recipients were White, 35% were Hispanic, and about 16% were Black. This information does not include every patient treated with TPOXX, the agency said, as providers can begin treatment before submitting paperwork. As of Aug. 18, the CDC had received 400 patient intake forms for TPOXX, according to its website.
The agency has yet to release data on vaccination rates, which Dr. Hubach is eager to see. Demographic information on who is receiving vaccinations, and where, can illuminate issues with access as vaccine eligibility continues to expand. “Vaccination is probably going to be the largest tool within our toolbox to try to inhibit disease acquisition and spread,” he said.
A version of this article first appeared on Medscape.com.
Commentary: Gastric Cancer Surgery Trials, September 2022
Surgical resection plays a critical role in the management of early-stage gastric cancer. Depending on the tumor stage and location, there are different surgical approaches. Complications associated with surgical resection can significantly affect quality of life and ability to receive subsequent treatment. With recent advances in minimally invasive approaches, laparoscopic resections are emerging as an attractive option for patients undergoing oncologic surgeries.
The KLASS-02 trial was a multicenter, randomized, controlled, noninferiority clinical trial, which enrolled 1050 patients with locally advanced gastric cancer. Of the enrolled patients, 974 patients underwent R0 resection either by laparoscopic (n = 492) or open (n = 482) distal gastrectomy. In the previous readout of this study with 3 years of follow-up, laparoscopic distal gastrectomy had noninferior oncologic outcomes compared with open surgery for locally advanced gastric cancer. Son and colleagues are now reporting 5-year follow-up results. Overall survival (OS; 88.9% vs 88.7%; P = .30) and relapse-free survival (79.5% vs 81.1%; P = .658) rates were similar in both surgical groups. The pattern of recurrences was similar between the two groups as well, with peroneal (42.1% of patients) and hematogenous (20.8%) being the most frequent ones. However, patients who underwent laparoscopic vs open distal gastrectomy had a significantly lower late complication rate (6.5% vs 11.0%; P = .01). This study demonstrates that laparoscopic distal gastrectomy is an appropriate alternative to open distal gastrectomy and should be offered to patients who are treated in centers with experience in performing these types of operations.
Peritoneal metastasis is a common site for the spread of gastric cancer. As such, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of this disease has been explored in a number of studies. The effectiveness of prophylactic HIPEC during resection of early-stage gastric cancer remains unknown.
Shen and colleagues conducted a propensity score-matching analysis looking at the efficacy and safety of HIPEC in this setting. The study evaluated outcomes of 395 patients with locally advanced gastric cancer who underwent resection with (n = 146) or without HIPEC (n = 248). In the HIPEC group, OS compared favorably to the surgery-only group (69.9% vs 40.8%, P = .049) and 2-year relapse-free survival was higher with HIPEC (60.7% vs 31.6%, P = .049).
Previously, the CYTO-CHIP propensity score analysis study performed in France demonstrated that HIPEC in addition to cytoreductive surgery resulted in improved OS in patients with advanced gastric cancer and peritoneal metastasis compared to cytoreduction surgery alone.1 However, with both of these reports, interpretation of the results carries inherent limitations that are associated with retrospective study design. Prior prospective studies, on the other hand, had mixed results. An ongoing phase 3 prospective study of D2 resection and HIPEC in locally advanced gastric carcinoma (GASTRICHIP) will hopefully provide a definitive answer regarding the benefit of HIPEC in early-stage gastric cancer management (NCT01882933). Ultimately, going forward, the role of HIPEC in early-stage disease will need to be examined in a prospective study with carefully selected patients, using the latest biomarkers and systemic therapies.
Mismatch repair protein deficient (dMMR) or microsatellite unstable gastric cancer (MSI-H) have distinct biologic behaviors and treatment responses. They are much more responsive to immune checkpoint inhibitors in the metastatic setting. In early-stage disease, exploratory analysis of patients with MSI-H tumors previously enrolled in the perioperative MAGIC trial, revealed that patients with MSI-H tumors had a better prognosis when treated with surgery alone, and they potentially experienced detrimental effects from chemotherapy.2
The GERCOR NEONIPIGA single-arm phase 2 study enrolled 32 patients with resectable dMMR/MSI-H gastric and gastroesophageal junction tumors.3 Patients were treated with 240-mg neoadjuvant nivolumab once every 2 weeks six times and 1-mg/kg ipilimumab once every 6 weeks twice, followed by surgery and 480-mg adjuvant nivolumab once every 4 weeks nine times. Twenty-nine patients underwent resection. All resections were with negative margins (R0). Pathologic complete response was seen in 17 (58.6%) of patients. As of the February 2022 data cutoff, with a median duration of follow-up of 14.9 months, 30 out of 31 patients with early-stage disease remained alive and without recurrence or progression (one evaluable patient had metastatic disease).
These results certainly support further investigation of immunotherapy use in this patient population. However, in the absence of prospective randomized data, the combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) remains the standard of care in those who can tolerate it. For patients with MSI-H tumors who are not candidates for combination chemotherapy or whose tumors are progressing on chemotherapy, neoadjuvant immunotherapy is certainly a good option to consider.
Additional References
1. Bonnot P-E et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): A propensity score analysis. J Clin Oncol. 2019;37:2028-2040. Doi: 10.1200/JCO.18.01688
2. Smyth EC et al. Mismatch repair deficiency, microsatellite instability, and survival: An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762
3. André T et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: The GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022 (Aug 15. Doi: 10.1200/JCO.22.00686
Surgical resection plays a critical role in the management of early-stage gastric cancer. Depending on the tumor stage and location, there are different surgical approaches. Complications associated with surgical resection can significantly affect quality of life and ability to receive subsequent treatment. With recent advances in minimally invasive approaches, laparoscopic resections are emerging as an attractive option for patients undergoing oncologic surgeries.
The KLASS-02 trial was a multicenter, randomized, controlled, noninferiority clinical trial, which enrolled 1050 patients with locally advanced gastric cancer. Of the enrolled patients, 974 patients underwent R0 resection either by laparoscopic (n = 492) or open (n = 482) distal gastrectomy. In the previous readout of this study with 3 years of follow-up, laparoscopic distal gastrectomy had noninferior oncologic outcomes compared with open surgery for locally advanced gastric cancer. Son and colleagues are now reporting 5-year follow-up results. Overall survival (OS; 88.9% vs 88.7%; P = .30) and relapse-free survival (79.5% vs 81.1%; P = .658) rates were similar in both surgical groups. The pattern of recurrences was similar between the two groups as well, with peroneal (42.1% of patients) and hematogenous (20.8%) being the most frequent ones. However, patients who underwent laparoscopic vs open distal gastrectomy had a significantly lower late complication rate (6.5% vs 11.0%; P = .01). This study demonstrates that laparoscopic distal gastrectomy is an appropriate alternative to open distal gastrectomy and should be offered to patients who are treated in centers with experience in performing these types of operations.
Peritoneal metastasis is a common site for the spread of gastric cancer. As such, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of this disease has been explored in a number of studies. The effectiveness of prophylactic HIPEC during resection of early-stage gastric cancer remains unknown.
Shen and colleagues conducted a propensity score-matching analysis looking at the efficacy and safety of HIPEC in this setting. The study evaluated outcomes of 395 patients with locally advanced gastric cancer who underwent resection with (n = 146) or without HIPEC (n = 248). In the HIPEC group, OS compared favorably to the surgery-only group (69.9% vs 40.8%, P = .049) and 2-year relapse-free survival was higher with HIPEC (60.7% vs 31.6%, P = .049).
Previously, the CYTO-CHIP propensity score analysis study performed in France demonstrated that HIPEC in addition to cytoreductive surgery resulted in improved OS in patients with advanced gastric cancer and peritoneal metastasis compared to cytoreduction surgery alone.1 However, with both of these reports, interpretation of the results carries inherent limitations that are associated with retrospective study design. Prior prospective studies, on the other hand, had mixed results. An ongoing phase 3 prospective study of D2 resection and HIPEC in locally advanced gastric carcinoma (GASTRICHIP) will hopefully provide a definitive answer regarding the benefit of HIPEC in early-stage gastric cancer management (NCT01882933). Ultimately, going forward, the role of HIPEC in early-stage disease will need to be examined in a prospective study with carefully selected patients, using the latest biomarkers and systemic therapies.
Mismatch repair protein deficient (dMMR) or microsatellite unstable gastric cancer (MSI-H) have distinct biologic behaviors and treatment responses. They are much more responsive to immune checkpoint inhibitors in the metastatic setting. In early-stage disease, exploratory analysis of patients with MSI-H tumors previously enrolled in the perioperative MAGIC trial, revealed that patients with MSI-H tumors had a better prognosis when treated with surgery alone, and they potentially experienced detrimental effects from chemotherapy.2
The GERCOR NEONIPIGA single-arm phase 2 study enrolled 32 patients with resectable dMMR/MSI-H gastric and gastroesophageal junction tumors.3 Patients were treated with 240-mg neoadjuvant nivolumab once every 2 weeks six times and 1-mg/kg ipilimumab once every 6 weeks twice, followed by surgery and 480-mg adjuvant nivolumab once every 4 weeks nine times. Twenty-nine patients underwent resection. All resections were with negative margins (R0). Pathologic complete response was seen in 17 (58.6%) of patients. As of the February 2022 data cutoff, with a median duration of follow-up of 14.9 months, 30 out of 31 patients with early-stage disease remained alive and without recurrence or progression (one evaluable patient had metastatic disease).
These results certainly support further investigation of immunotherapy use in this patient population. However, in the absence of prospective randomized data, the combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) remains the standard of care in those who can tolerate it. For patients with MSI-H tumors who are not candidates for combination chemotherapy or whose tumors are progressing on chemotherapy, neoadjuvant immunotherapy is certainly a good option to consider.
Additional References
1. Bonnot P-E et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): A propensity score analysis. J Clin Oncol. 2019;37:2028-2040. Doi: 10.1200/JCO.18.01688
2. Smyth EC et al. Mismatch repair deficiency, microsatellite instability, and survival: An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762
3. André T et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: The GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022 (Aug 15. Doi: 10.1200/JCO.22.00686
Surgical resection plays a critical role in the management of early-stage gastric cancer. Depending on the tumor stage and location, there are different surgical approaches. Complications associated with surgical resection can significantly affect quality of life and ability to receive subsequent treatment. With recent advances in minimally invasive approaches, laparoscopic resections are emerging as an attractive option for patients undergoing oncologic surgeries.
The KLASS-02 trial was a multicenter, randomized, controlled, noninferiority clinical trial, which enrolled 1050 patients with locally advanced gastric cancer. Of the enrolled patients, 974 patients underwent R0 resection either by laparoscopic (n = 492) or open (n = 482) distal gastrectomy. In the previous readout of this study with 3 years of follow-up, laparoscopic distal gastrectomy had noninferior oncologic outcomes compared with open surgery for locally advanced gastric cancer. Son and colleagues are now reporting 5-year follow-up results. Overall survival (OS; 88.9% vs 88.7%; P = .30) and relapse-free survival (79.5% vs 81.1%; P = .658) rates were similar in both surgical groups. The pattern of recurrences was similar between the two groups as well, with peroneal (42.1% of patients) and hematogenous (20.8%) being the most frequent ones. However, patients who underwent laparoscopic vs open distal gastrectomy had a significantly lower late complication rate (6.5% vs 11.0%; P = .01). This study demonstrates that laparoscopic distal gastrectomy is an appropriate alternative to open distal gastrectomy and should be offered to patients who are treated in centers with experience in performing these types of operations.
Peritoneal metastasis is a common site for the spread of gastric cancer. As such, the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of this disease has been explored in a number of studies. The effectiveness of prophylactic HIPEC during resection of early-stage gastric cancer remains unknown.
Shen and colleagues conducted a propensity score-matching analysis looking at the efficacy and safety of HIPEC in this setting. The study evaluated outcomes of 395 patients with locally advanced gastric cancer who underwent resection with (n = 146) or without HIPEC (n = 248). In the HIPEC group, OS compared favorably to the surgery-only group (69.9% vs 40.8%, P = .049) and 2-year relapse-free survival was higher with HIPEC (60.7% vs 31.6%, P = .049).
Previously, the CYTO-CHIP propensity score analysis study performed in France demonstrated that HIPEC in addition to cytoreductive surgery resulted in improved OS in patients with advanced gastric cancer and peritoneal metastasis compared to cytoreduction surgery alone.1 However, with both of these reports, interpretation of the results carries inherent limitations that are associated with retrospective study design. Prior prospective studies, on the other hand, had mixed results. An ongoing phase 3 prospective study of D2 resection and HIPEC in locally advanced gastric carcinoma (GASTRICHIP) will hopefully provide a definitive answer regarding the benefit of HIPEC in early-stage gastric cancer management (NCT01882933). Ultimately, going forward, the role of HIPEC in early-stage disease will need to be examined in a prospective study with carefully selected patients, using the latest biomarkers and systemic therapies.
Mismatch repair protein deficient (dMMR) or microsatellite unstable gastric cancer (MSI-H) have distinct biologic behaviors and treatment responses. They are much more responsive to immune checkpoint inhibitors in the metastatic setting. In early-stage disease, exploratory analysis of patients with MSI-H tumors previously enrolled in the perioperative MAGIC trial, revealed that patients with MSI-H tumors had a better prognosis when treated with surgery alone, and they potentially experienced detrimental effects from chemotherapy.2
The GERCOR NEONIPIGA single-arm phase 2 study enrolled 32 patients with resectable dMMR/MSI-H gastric and gastroesophageal junction tumors.3 Patients were treated with 240-mg neoadjuvant nivolumab once every 2 weeks six times and 1-mg/kg ipilimumab once every 6 weeks twice, followed by surgery and 480-mg adjuvant nivolumab once every 4 weeks nine times. Twenty-nine patients underwent resection. All resections were with negative margins (R0). Pathologic complete response was seen in 17 (58.6%) of patients. As of the February 2022 data cutoff, with a median duration of follow-up of 14.9 months, 30 out of 31 patients with early-stage disease remained alive and without recurrence or progression (one evaluable patient had metastatic disease).
These results certainly support further investigation of immunotherapy use in this patient population. However, in the absence of prospective randomized data, the combination of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) remains the standard of care in those who can tolerate it. For patients with MSI-H tumors who are not candidates for combination chemotherapy or whose tumors are progressing on chemotherapy, neoadjuvant immunotherapy is certainly a good option to consider.
Additional References
1. Bonnot P-E et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastases (CYTO-CHIP study): A propensity score analysis. J Clin Oncol. 2019;37:2028-2040. Doi: 10.1200/JCO.18.01688
2. Smyth EC et al. Mismatch repair deficiency, microsatellite instability, and survival: An exploratory analysis of the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial. JAMA Oncol. 2017;3:1197-1203. Doi: 10.1001/jamaoncol.2016.6762
3. André T et al. Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in localized deficient mismatch repair/microsatellite instability-high gastric or esophagogastric junction adenocarcinoma: The GERCOR NEONIPIGA phase II study. J Clin Oncol. 2022 (Aug 15. Doi: 10.1200/JCO.22.00686
Commentary: Diet and Colorectal Cancer, September 2022
This month's journal articles in the field of colorectal cancer research lack the cachet of some of the high-profile dispatches we discussed in previous editions of Clinical Edge. Nonetheless, there are several interesting reports this month.
The first is a clinical trial report that came out of China investigating the possible synergistic effect of high-dose vitamin C with chemotherapy in the first-line treatment of metastatic colorectal cancer (mCRC). The study was based on preclinical data that showed a synergistic increase in cancer cell death with chemotherapy plus high-dose vitamin C in in vitro models. Wang and colleagues randomly assigned 442 treatment-naive patients with mCRC to receive folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab with or without 1.5 g/kg vitamin C intravenously on days 1-3 of each chemotherapy cycle.
The study's primary endpoint was progression-free survival (PFS), and patients were stratified on the basis of tumor sidedness and use of bevacizumab. PFS for the intention-to-treat group was unaffected by use of vitamin C (hazard ratio [HR] 0.86; 95% CI 0.70-1.05; P = .1). However, patients whose tumors harbored RAS mutations had a PFS that was significantly improved in the vitamin C arm (9.2 vs 7.8 months; HR 0.67; 95% CI 0.50-0.91; P = .01). Additionally, treatment-related adverse events were no more common in the treatment arm than in the control arm. Although I seldom draw clinical conclusions from subgroup analyses, I find it comforting to know that high-dose vitamin C is at least safe and potentially helpful for some patients. Many of my patients through the years have asked me about the utility of high-dose vitamin C. At least I can now inform them that the treatment is unlikely to cause physical harm or substantially decrease the efficacy of chemotherapy.
The second article I will discuss focuses on dietary fat intake and its potential effects on mortality and cancer progression in patients with mCRC. Using a food-frequency questionnaire, the authors of the study assessed the diets of 1194 patients who had been part of a previous cooperative group study for patients with treatment-naive mCRC (Van Blarigan et al). Over a median follow-up of 6.1 years, patients with the highest median intake of vegetable fats (23.5% kcal/d; interquartile range [IQR] 21.6%-25.7% kcal/d) vs the lowest intake (11.6% kcal/d; IQR 10.1%-12.7% kcal/d) showed a lower risk for all-cause mortality (adjusted HR 0.79; 95% CI 0.63-1.00) and cancer progression or death (adjusted HR 0.71; 95% CI 0.57-0.88). Although this study's results were not unexpected given data that have been published in the past, it builds on previous work as it shows the specific benefits of vegetable fats vis-à-vis animal fats, which are detrimental to survival. Oncologists continue to benefit from these studies because they allow us to give more specific dietary recommendations for high fat-containing vegan foods, such as avocados, olives, and nuts.
This month's journal articles in the field of colorectal cancer research lack the cachet of some of the high-profile dispatches we discussed in previous editions of Clinical Edge. Nonetheless, there are several interesting reports this month.
The first is a clinical trial report that came out of China investigating the possible synergistic effect of high-dose vitamin C with chemotherapy in the first-line treatment of metastatic colorectal cancer (mCRC). The study was based on preclinical data that showed a synergistic increase in cancer cell death with chemotherapy plus high-dose vitamin C in in vitro models. Wang and colleagues randomly assigned 442 treatment-naive patients with mCRC to receive folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab with or without 1.5 g/kg vitamin C intravenously on days 1-3 of each chemotherapy cycle.
The study's primary endpoint was progression-free survival (PFS), and patients were stratified on the basis of tumor sidedness and use of bevacizumab. PFS for the intention-to-treat group was unaffected by use of vitamin C (hazard ratio [HR] 0.86; 95% CI 0.70-1.05; P = .1). However, patients whose tumors harbored RAS mutations had a PFS that was significantly improved in the vitamin C arm (9.2 vs 7.8 months; HR 0.67; 95% CI 0.50-0.91; P = .01). Additionally, treatment-related adverse events were no more common in the treatment arm than in the control arm. Although I seldom draw clinical conclusions from subgroup analyses, I find it comforting to know that high-dose vitamin C is at least safe and potentially helpful for some patients. Many of my patients through the years have asked me about the utility of high-dose vitamin C. At least I can now inform them that the treatment is unlikely to cause physical harm or substantially decrease the efficacy of chemotherapy.
The second article I will discuss focuses on dietary fat intake and its potential effects on mortality and cancer progression in patients with mCRC. Using a food-frequency questionnaire, the authors of the study assessed the diets of 1194 patients who had been part of a previous cooperative group study for patients with treatment-naive mCRC (Van Blarigan et al). Over a median follow-up of 6.1 years, patients with the highest median intake of vegetable fats (23.5% kcal/d; interquartile range [IQR] 21.6%-25.7% kcal/d) vs the lowest intake (11.6% kcal/d; IQR 10.1%-12.7% kcal/d) showed a lower risk for all-cause mortality (adjusted HR 0.79; 95% CI 0.63-1.00) and cancer progression or death (adjusted HR 0.71; 95% CI 0.57-0.88). Although this study's results were not unexpected given data that have been published in the past, it builds on previous work as it shows the specific benefits of vegetable fats vis-à-vis animal fats, which are detrimental to survival. Oncologists continue to benefit from these studies because they allow us to give more specific dietary recommendations for high fat-containing vegan foods, such as avocados, olives, and nuts.
This month's journal articles in the field of colorectal cancer research lack the cachet of some of the high-profile dispatches we discussed in previous editions of Clinical Edge. Nonetheless, there are several interesting reports this month.
The first is a clinical trial report that came out of China investigating the possible synergistic effect of high-dose vitamin C with chemotherapy in the first-line treatment of metastatic colorectal cancer (mCRC). The study was based on preclinical data that showed a synergistic increase in cancer cell death with chemotherapy plus high-dose vitamin C in in vitro models. Wang and colleagues randomly assigned 442 treatment-naive patients with mCRC to receive folinic acid, fluorouracil, and oxaliplatin (FOLFOX) and bevacizumab with or without 1.5 g/kg vitamin C intravenously on days 1-3 of each chemotherapy cycle.
The study's primary endpoint was progression-free survival (PFS), and patients were stratified on the basis of tumor sidedness and use of bevacizumab. PFS for the intention-to-treat group was unaffected by use of vitamin C (hazard ratio [HR] 0.86; 95% CI 0.70-1.05; P = .1). However, patients whose tumors harbored RAS mutations had a PFS that was significantly improved in the vitamin C arm (9.2 vs 7.8 months; HR 0.67; 95% CI 0.50-0.91; P = .01). Additionally, treatment-related adverse events were no more common in the treatment arm than in the control arm. Although I seldom draw clinical conclusions from subgroup analyses, I find it comforting to know that high-dose vitamin C is at least safe and potentially helpful for some patients. Many of my patients through the years have asked me about the utility of high-dose vitamin C. At least I can now inform them that the treatment is unlikely to cause physical harm or substantially decrease the efficacy of chemotherapy.
The second article I will discuss focuses on dietary fat intake and its potential effects on mortality and cancer progression in patients with mCRC. Using a food-frequency questionnaire, the authors of the study assessed the diets of 1194 patients who had been part of a previous cooperative group study for patients with treatment-naive mCRC (Van Blarigan et al). Over a median follow-up of 6.1 years, patients with the highest median intake of vegetable fats (23.5% kcal/d; interquartile range [IQR] 21.6%-25.7% kcal/d) vs the lowest intake (11.6% kcal/d; IQR 10.1%-12.7% kcal/d) showed a lower risk for all-cause mortality (adjusted HR 0.79; 95% CI 0.63-1.00) and cancer progression or death (adjusted HR 0.71; 95% CI 0.57-0.88). Although this study's results were not unexpected given data that have been published in the past, it builds on previous work as it shows the specific benefits of vegetable fats vis-à-vis animal fats, which are detrimental to survival. Oncologists continue to benefit from these studies because they allow us to give more specific dietary recommendations for high fat-containing vegan foods, such as avocados, olives, and nuts.