A potentially deadly bacteria has been found in U.S. soil and water samples for the first time, according to a new alert from the Centers for Disease Control and Prevention.

The bacteria, Burkholderia pseudomallei, was found along the Gulf Coast region in southern Mississippi. Typically, the bacteria are in tropical and subtropical climates, especially in parts of Southeast Asia, northern Australia, Central America, South America, Puerto Rico, and the U.S. Virgin Islands.

The bacteria can cause melioidosis, a rare and serious infectious disease that spreads to animals and humans through contact with contaminated soil and water via cuts, wounds, mucous membranes, breathing the bacteria in, or eating or drinking it. Worldwide, the disease is fatal in 10%-50% of those who become infected.

CDC and state officials are investigating the samples to find out how widespread the bacteria are within the United States. So far, modeling suggests that the environmental conditions on the Gulf Coast support the growth of B. pseudomallei.

“It is unclear how long the bacteria has been in the environment and where else it might be found in the U.S.,” according to the CDC statement. “CDC is alerting clinicians throughout the country of this discovery through a national health advisory, reminding them to be aware of the signs and symptoms of melioidosis and to consider melioidosis in patients that present with symptoms of the disease.”

Two unrelated people who live near the Gulf Coast region of Mississippi became sick with melioidosis recently – one in July 2020 and one in May 2022. Neither had traveled outside of the United States. The cases led the CDC and the Mississippi State Department of Health to collect environmental samples and test household products at the patients’ homes in June 2022. Three of the samples taken from soil and puddle water in the 2020 case tested positive for the bacteria.

Genomic sequencing revealed that both patients were infected with the same strain of the bacteria from the Western Hemisphere. They were hospitalized with sepsis due to pneumonia and had known risk factors for melioidosis. Both patients recovered after they were treated with antibiotics.

An average of 12 melioidosis cases are diagnosed in the United States each year, with most in people with recent travel to a country where the bacteria is endemic, or regularly found. Cases have also been linked to contaminated products imported from endemic countries. In late 2021, four cases in four states – Georgia, Kansas, Minnesota, and Texas – were linked to a contaminated aromatherapy spray that was imported, and Walmart issued a recall in November of that year, according to a CDC announcement. Two of the four people died.

Given the small number of cases found in the United States, the CDC believes the risk of melioidosis for the general population continues to be “very low,” and the risk of person-to-person spread is considered “extremely low.” But people who live on the Gulf Coast of Mississippi and who have health conditions that may put them at a higher risk, such as diabetes, chronic kidney disease, chronic lung disease, excessive alcohol use, and immunosuppressive conditions, should protect themselves.

The CDC recommends avoiding contact with soil or muddy water, particularly after heavy rains, and protecting open wounds with waterproof bandages. People should also wear waterproof boots when gardening, working in the yard, or doing agricultural work, which can prevent infection through the feet and lower legs, especially after flooding or storms. People should also wear gloves to protect their hands when working directly with soil.

Melioidosis has a wide range of symptoms, including fever, joint pain, headaches, coughing, chest pain, and belly pain. It can also cause conditions such as pneumonia, abscesses, and blood infections. The disease can infect any organ, including the brain. In most cases, symptoms appear within 1-21 days after exposure, with an average of 7 days after exposure.

The CDC’s health advisory for health professionals and public health officials shows that melioidosis is now considered to be locally endemic in areas of the Gulf Coast region in Mississippi.

“Once well-established in the soil, B. pseudomallei cannot feasibly be removed from the soil,” according to the advisory. “Public health efforts should focus primarily on improving identification of cases so that appropriate treatment can be administered.”

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

A potentially deadly bacteria has been found in U.S. soil and water samples for the first time, according to a new alert from the Centers for Disease Control and Prevention.

The bacteria, Burkholderia pseudomallei, was found along the Gulf Coast region in southern Mississippi. Typically, the bacteria are in tropical and subtropical climates, especially in parts of Southeast Asia, northern Australia, Central America, South America, Puerto Rico, and the U.S. Virgin Islands.

The bacteria can cause melioidosis, a rare and serious infectious disease that spreads to animals and humans through contact with contaminated soil and water via cuts, wounds, mucous membranes, breathing the bacteria in, or eating or drinking it. Worldwide, the disease is fatal in 10%-50% of those who become infected.

CDC and state officials are investigating the samples to find out how widespread the bacteria are within the United States. So far, modeling suggests that the environmental conditions on the Gulf Coast support the growth of B. pseudomallei.

“It is unclear how long the bacteria has been in the environment and where else it might be found in the U.S.,” according to the CDC statement. “CDC is alerting clinicians throughout the country of this discovery through a national health advisory, reminding them to be aware of the signs and symptoms of melioidosis and to consider melioidosis in patients that present with symptoms of the disease.”

Two unrelated people who live near the Gulf Coast region of Mississippi became sick with melioidosis recently – one in July 2020 and one in May 2022. Neither had traveled outside of the United States. The cases led the CDC and the Mississippi State Department of Health to collect environmental samples and test household products at the patients’ homes in June 2022. Three of the samples taken from soil and puddle water in the 2020 case tested positive for the bacteria.

Genomic sequencing revealed that both patients were infected with the same strain of the bacteria from the Western Hemisphere. They were hospitalized with sepsis due to pneumonia and had known risk factors for melioidosis. Both patients recovered after they were treated with antibiotics.

An average of 12 melioidosis cases are diagnosed in the United States each year, with most in people with recent travel to a country where the bacteria is endemic, or regularly found. Cases have also been linked to contaminated products imported from endemic countries. In late 2021, four cases in four states – Georgia, Kansas, Minnesota, and Texas – were linked to a contaminated aromatherapy spray that was imported, and Walmart issued a recall in November of that year, according to a CDC announcement. Two of the four people died.

Given the small number of cases found in the United States, the CDC believes the risk of melioidosis for the general population continues to be “very low,” and the risk of person-to-person spread is considered “extremely low.” But people who live on the Gulf Coast of Mississippi and who have health conditions that may put them at a higher risk, such as diabetes, chronic kidney disease, chronic lung disease, excessive alcohol use, and immunosuppressive conditions, should protect themselves.

The CDC recommends avoiding contact with soil or muddy water, particularly after heavy rains, and protecting open wounds with waterproof bandages. People should also wear waterproof boots when gardening, working in the yard, or doing agricultural work, which can prevent infection through the feet and lower legs, especially after flooding or storms. People should also wear gloves to protect their hands when working directly with soil.

Melioidosis has a wide range of symptoms, including fever, joint pain, headaches, coughing, chest pain, and belly pain. It can also cause conditions such as pneumonia, abscesses, and blood infections. The disease can infect any organ, including the brain. In most cases, symptoms appear within 1-21 days after exposure, with an average of 7 days after exposure.

The CDC’s health advisory for health professionals and public health officials shows that melioidosis is now considered to be locally endemic in areas of the Gulf Coast region in Mississippi.

“Once well-established in the soil, B. pseudomallei cannot feasibly be removed from the soil,” according to the advisory. “Public health efforts should focus primarily on improving identification of cases so that appropriate treatment can be administered.”

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

A potentially deadly bacteria has been found in U.S. soil and water samples for the first time, according to a new alert from the Centers for Disease Control and Prevention.

The bacteria, Burkholderia pseudomallei, was found along the Gulf Coast region in southern Mississippi. Typically, the bacteria are in tropical and subtropical climates, especially in parts of Southeast Asia, northern Australia, Central America, South America, Puerto Rico, and the U.S. Virgin Islands.

The bacteria can cause melioidosis, a rare and serious infectious disease that spreads to animals and humans through contact with contaminated soil and water via cuts, wounds, mucous membranes, breathing the bacteria in, or eating or drinking it. Worldwide, the disease is fatal in 10%-50% of those who become infected.

CDC and state officials are investigating the samples to find out how widespread the bacteria are within the United States. So far, modeling suggests that the environmental conditions on the Gulf Coast support the growth of B. pseudomallei.

“It is unclear how long the bacteria has been in the environment and where else it might be found in the U.S.,” according to the CDC statement. “CDC is alerting clinicians throughout the country of this discovery through a national health advisory, reminding them to be aware of the signs and symptoms of melioidosis and to consider melioidosis in patients that present with symptoms of the disease.”

Two unrelated people who live near the Gulf Coast region of Mississippi became sick with melioidosis recently – one in July 2020 and one in May 2022. Neither had traveled outside of the United States. The cases led the CDC and the Mississippi State Department of Health to collect environmental samples and test household products at the patients’ homes in June 2022. Three of the samples taken from soil and puddle water in the 2020 case tested positive for the bacteria.

Genomic sequencing revealed that both patients were infected with the same strain of the bacteria from the Western Hemisphere. They were hospitalized with sepsis due to pneumonia and had known risk factors for melioidosis. Both patients recovered after they were treated with antibiotics.

An average of 12 melioidosis cases are diagnosed in the United States each year, with most in people with recent travel to a country where the bacteria is endemic, or regularly found. Cases have also been linked to contaminated products imported from endemic countries. In late 2021, four cases in four states – Georgia, Kansas, Minnesota, and Texas – were linked to a contaminated aromatherapy spray that was imported, and Walmart issued a recall in November of that year, according to a CDC announcement. Two of the four people died.

Given the small number of cases found in the United States, the CDC believes the risk of melioidosis for the general population continues to be “very low,” and the risk of person-to-person spread is considered “extremely low.” But people who live on the Gulf Coast of Mississippi and who have health conditions that may put them at a higher risk, such as diabetes, chronic kidney disease, chronic lung disease, excessive alcohol use, and immunosuppressive conditions, should protect themselves.

The CDC recommends avoiding contact with soil or muddy water, particularly after heavy rains, and protecting open wounds with waterproof bandages. People should also wear waterproof boots when gardening, working in the yard, or doing agricultural work, which can prevent infection through the feet and lower legs, especially after flooding or storms. People should also wear gloves to protect their hands when working directly with soil.

Melioidosis has a wide range of symptoms, including fever, joint pain, headaches, coughing, chest pain, and belly pain. It can also cause conditions such as pneumonia, abscesses, and blood infections. The disease can infect any organ, including the brain. In most cases, symptoms appear within 1-21 days after exposure, with an average of 7 days after exposure.

The CDC’s health advisory for health professionals and public health officials shows that melioidosis is now considered to be locally endemic in areas of the Gulf Coast region in Mississippi.

“Once well-established in the soil, B. pseudomallei cannot feasibly be removed from the soil,” according to the advisory. “Public health efforts should focus primarily on improving identification of cases so that appropriate treatment can be administered.”

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

Many scientists and public health experts have long said the coronavirus that has caused a global pandemic originated in a marketplace in Wuhan, China. Now, two new studies strengthen that argument.

The original spread of the virus was a one-two punch, the studies found. Twice, the virus jumped from animals to humans. Virus genetics and outbreak modeling in one study revealed two strains released a few weeks apart in November and December 2019.

“Now I realize it sounds like I just said that a once-in-a-generation event happened twice in short succession, and pandemics are indeed rare,” Joel O. Wertheim, PhD, said at a briefing sponsored by the American Association for the Advancement of Science.

A unique storm of factors had to be present for the outbreak to blow up into a pandemic: Animals carrying a virus that could spread to humans, close human contact with these animals, and a city large enough for the infection to take off before it could be contained are examples.

Unluckily for us humans, this coronavirus – SARS-CoV-2 – is a “generalist virus” capable of infecting many animals, including humans.

“Once all the conditions are in place ... the barriers to spillover have been lowered,” said Dr. Wertheim, a researcher in genetic and molecular networks at the University of California, San Diego. In fact, beyond the two strains of the virus that took hold, there were likely up to two dozen more times where people got the virus but did not spread it far and wide, and it died out.

Overall, the odds were against the virus – 78% of the time, the “introduction” to humans was likely to go extinct, the study showed.

The research revealed the COVID-19 pandemic started small.

“Our model shows that there were likely only a few dozen infections, and only several hospitalizations due to COVID-19, by early December,” said Jonathan Pekar, a graduate student working with Dr. Wertheim.

In Wuhan in late 2019, Mr. Pekar said, there was not a single positive coronavirus sample from thousands of samples from healthy blood donors tested between September and December. Likewise, not one blood sample from patients hospitalized with flu-like illness from October to December 2019 tested positive for SARS-CoV-2.
 

Mapping the outbreak

A second study published in the journal Science mapped out the earliest COVID-19 cases. This effort showed a tight cluster around the wholesale seafood market inside Wuhan, a city of 11 million residents.

When researchers tried other scenarios – modeling outbreaks in other parts of the city – the pattern did not hold. Again, the Wuhan market appeared to be ground zero for the start of the pandemic.

Michael Worobey, PhD, and colleagues used data from Chinese scientists and the World Health Organization for the study.

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centered on this market,” said Dr. Worobey, head of ecology and evolutionary biology at the University of Arizona, Tucson.

The highest density of cases, in a city of 8,000 square kilometers, was a “very, very small area of about a third of a kilometer square,” he said.

The outbreak pattern showed the Wuhan market “smack dab in the middle.”

So if it started with infected workers at the market, how did it spread from there? It’s likely the virus got into the community as the vendors at the market went to local shops, infecting people in those stores. Then local community members not linked to the market started getting the virus, Dr. Worobey said.

The investigators also identified which stalls in the market were most likely involved, a sort of internal clustering. “That clustering is very, very specifically in the parts of the market where ... they were selling wildlife, including, for example, raccoon dogs and other animals that we know are susceptible to infection with SARS-CoV-2,” said Kristian Andersen, PhD, director of infectious disease genomics at the Scripps Research Institute in La Jolla, Calif.

What remains unknown is which animal or animals carried the virus, although the raccoon dog – an animal similar to a fox that is native to parts of Asia – remains central to most theories. In addition, many of the farms supplying animals to the market have since been closed, making it challenging for researchers to figure out exactly where infected animals came from.

“We don’t know necessarily, but raccoon dogs were sold at this market all the way up to the beginning of the pandemic,” Dr. Andersen said.
 

Not ruling out other theories

People who believe SARS-CoV-2 was released from a laboratory in China at first included Dr. Worobey himself. “I’ve in the past been much more open to the lab leak idea,” he said. “And published that in a letter in Science” in November 2021.

The letter was “much more influential than I thought it would be in ways that I think it turned out to be quite damaging,” he said. As more evidence emerged since then, Dr. Worobey said he came around to the Wuhan market source theory.

Dr. Andersen agreed he was more open to the lab-leak theory at first. “I was quite convinced of the lab leak myself until we dove into this very carefully and looked at it much closer,” he said. Newer evidence convinced him “that actually, the data points to this particular market.”

“Have we disproved the lab-leak theory? No,” Dr. Anderson said. “Will we ever be able to? No.” But the Wuhan market origin scenario is more plausible. “I would say these two papers combined present the strongest evidence of that to date.”

Identifying the source of the outbreak that led to the COVID-19 pandemic is based in science, Dr. Andersen said. “What we’re trying to understand is the origin of the pandemic. We’re not trying to place blame.”
 

Future directions

“With pandemics being pandemics, they affect all of us,” Dr. Andersen said. “We can’t prevent these kinds of events that led to the COVID-19 pandemic. But what we can hope to do is to prevent outbreaks from becoming pandemics.”

Rapid reporting of data and cooperation are needed going forward, Dr. Andersen said. Very strong surveillance systems, including wastewater surveillance, could help monitor for SARS-CoV-2, and other pathogens of potential concern in the future as well.

It should be standard practice for medical professionals to be on alert for unusual respiratory infections too, the researchers said.

“It’s a bloody lucky thing that the doctors at the Shinwa hospital were so on the ball, that they noticed that these cases were something unusual at the end of December,” Dr. Worobey said. “It didn’t have to work out that way.”

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

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+/Getty Images

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

Help your patients understand their risks for NASH by sharing AGA patient education at www.gastro.org/NASH.

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+/Getty Images

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

Help your patients understand their risks for NASH by sharing AGA patient education at www.gastro.org/NASH.

A novel liquid biopsy test, which uses two circulating proteins, appears to be effective for diagnosing two major liver conditions, according to a new study published in Gut.

The test could allow clinicians to determine the staging of both liver fibrosis and nonalcoholic steatohepatitis, wrote the researchers led by Giulia Angelini, PhD, a postdoctoral fellow focused on nonalcoholic fatty liver disease pathophysiology at the Catholic University of the Sacred Heart in Rome.

ftwitty/E+/Getty Images

“The diagnosis of nonalcoholic steatohepatitis (NASH) currently relies on invasive liver biopsy,” they wrote. “There is, therefore, an urgent need to find noninvasive biomarkers for NASH diagnosis, disease progression, and intervention response monitoring.”

The research team sought to identify a biomarker and algorithm able to predict the presence and severity of nonalcoholic steatohepatitis (NASH) or liver fibrosis. The study evaluated two proteins found in circulating monocytes, which are a type of white blood cell: PLIN2 as a predictor of histological NASH and RAB14 levels as a predictor of liver fibrosis.

The multicenter study included 250 patients, with 100 subjects in the discovery cohort from the Bariatric Surgery Versus Nonalcoholic Steatohepatitis trial, or BRAVES, and 150 subjects in the validation cohort from the Liquid Biopsy for NASH and Liver Fibrosis trial, or LIBRA. The patients had histologically proven nonalcoholic fatty liver disease or NASH with or without fibrosis.

After careful molecular analysis, the research team used neural network classifiers to predict the presence of NASH and NASH stages. The analysis for the prediction of the presence of NASH produced an accuracy of 93% in the discovery cohort and 92% in the validation cohort. Sensitivity and specificity were 95% and 90% in the discovery group and 88% and 100% in the validation group, respectively. The research team also used a neural network analysis to predict the stages of NASH, which showed an accuracy of 85% in the discovery group and 85.2% in the validation cohort.

RAB14 was used to predict liver fibrosis with a logistic model that included waist circumference, age, plasma glucose, high-density lipoprotein, and alanine aminotransferase. In the discovery group, accuracy was 99.2%, sensitivity was 100%, and specificity was 95.8%. In the validation group, accuracy was 97.6%, sensitivity was 99%, and specificity was 89.6%.

When RAB14 was used as the only variable in the model, the accuracy, sensitivity, and specificity in the discovery cohort were 86.4%, 96%, and 45.8%, respectively. In the validation cohort, they were 92.4%, 96.9%, and 34.5%, respectively. In both cohorts, half of the subjects without fibrosis were erroneously predicted as having fibrosis, but the diagnosis of fibrosis was correctly predicted in nearly all subjects.

A limitation of the study is that only White subjects were enrolled, which limits the generalizability to other racial/ethnic groups, the investigators wrote, although they don’t expect differences would be seen in other groups.

“PLIN2 and RAB14 may permit diagnosis of NASH and/or liver fibrosis with a simple blood test,” they wrote. “Our biomarkers can be used in community and population studies permitting to investigate the real prevalence of NASH and liver fibrosis. Moreover, since it requires only blood sampling, they are potentially valuable tools for population-based and prevention studies in children.”
 

A step forward

“Obesity is a silent pandemic with an expected prevalence rate that will exceed 50% globally by 2030, of which 25% of the adults have fatty liver and approximately 6.5% with NASH, a progressive form of fatty liver,” said Kalyan Ram Bhamidimarri, MD, chief of hepatology and associate professor of clinical medicine at the University of Miami, who was not involved in the research. “Liver biopsy is the current clinical standard to diagnose NASH, but relying on an invasive procedure like liver biopsy that is fraught with several risks in a consistently growing volume of individuals with obesity is unsustainable.

Courtesy University of Miami

“So, there is an unmet need to diagnose NASH without invasive procedures such as liver biopsy,” he said. He pointed out that many of the alternatives to liver biopsy, such as liver stiffness measurements and scoring systems, pose their own difficulties.

On the other hand, he noted that “blood-based tests that correlate well with liver biopsy, the so-called wet biomarkers or liquid liver biopsy, are easier to perform, accessed widely, and could be tested frequently to assess efficacy of therapies.”

The study was funded by Elucidating Pathways of Steatohepatitis (EPOS Horizon 2020), Stratification of Obese Phenotypes to Optimize Future Obesity Therapy (SOPHIA IMI), Metadeq Inc., and support from the Transcampus Initiative. The study authors declared various competing interests, including some who serve as an advisor or stock option holder for Metadeq Limited. Dr. Bhamidimarri reported no relevant conflicts of interest.

Help your patients understand their risks for NASH by sharing AGA patient education at www.gastro.org/NASH.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

In the last 2 decades, the number of women receiving awards from the American College of Rheumatology, European Alliance of Associations for Rheumatology, and the British Society for Rheumatology has steadily increased, but the absolute percentage of female prize winners remains lower than male winners across the 41 total awards given by the three organizations, according to Thorsten Halling and colleagues at Heinrich-Heine-University in Düsseldorf, Germany.

The overall number of awards given by the three groups rose by 10% over the past 2 years. In 2021, 40% of awards given by the ACR went to females, compared with 48% by EULAR, and 50% by the BSR. However, the most prestigious prizes awarded by these groups were given less often to women, according to the researchers, who published their results online July 27, 2022, in The Lancet Rheumatology. They noted that during 2017-2021, just one in five top prizes from ACR went to a woman; once (20%) for the Presidential Gold Medal, and 26 times (23%) for the ACR Master Designation. During the same time period, only one woman (11%) received the EULAR Meritorious Service Award. In 2022, the EULAR Health Professionals in Rheumatology Lifetime Achievement Award was inaugurated and given to Christina Opava. As for the most important prizes of the BSR, the corresponding numbers for female recipients are 25% for the Michael Mason Award and 33% for the Garrod Award.” This pattern did not seem to change in 2022 at the BSR and EULAR annual meetings; the 2022 ACR annual meeting is in November.

ptasha/Getty Images

The trend is also seen in others fields, noted the researchers, who cited only one woman winning mathematics’ Fields Medal since it began in 1936 and female scientists winning only 7% of the Nobel Prize awards in the categories physiology or medicine, physics, and chemistry. In one larger study of 141 international research prizes that were awarded 3,445 times during 2001-2020, only 262 recipients were women.

Changing the status quo begins with awareness, according to the authors, who propose three strategies for prize juries to follow to raise the number of female awardees. “First, it is important to stimulate diversity among both nominees and the members of prize committees. Efforts to diversify the pool of nominees have already been initiated by large science prize players, such as the Royal Academy of Sciences in Sweden and the Wolf Foundation in Israel. This diversity should not only take gender into account, but also geographical region, ethnicity, and age. In the prize statutes, we recommend that the biological age of the applicants should no longer play a role for young scientist awards, but only the academic age. Second, if prizes are to be named after a person or people, we suggest that they should increasingly honor rheumatologists who are women to further increase their visibility in the field of rheumatology. We can note that, so far, no single award is named after a rheumatologist who is a woman. Third, we are convinced that more transparency around the nomination procedure will promote gender equity among the future prize winners.”

The authors had no conflicts of interest to declare.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

A procalcitonin-based algorithm could safely reduce unnecessary usage of antibiotics in patients with acute pancreatitis, based on results of a randomized controlled trial.

Physicians should consider incorporating the decision-making process into their daily practice, suggested lead author Ajith K. Siriwardena, MD, of Manchester (England) University and colleagues, who also recommended that the algorithm be added to future guidelines.

“Overuse of antibiotics and the resultant emergence of multidrug resistant microorganisms is a potent threat to the welfare of humanity in the 21st century,” the investigators wrote in The Lancet Gastroenterology & Hepatology.

Antibiotic overuse is common in cases of acute pancreatitis, they noted, because clinical features are typically insufficient to distinguish between inflammation and infection. While measuring procalcitonin can help can detect infection, “indiscriminate measurement” of the biomarker is not cost effective, according to the investigators, leading previous reviews and analyses to conclude that further research is needed before widespread usage can be recommended.

Dr. Siriwardena and colleagues aimed to meet this need by conducting a randomized controlled trial involving 260 patients hospitalized for acute pancreatitis at Manchester Royal Infirmary. Patients were randomized in a near 1:1 ratio. Both the intervention group (n = 132) and the control group (n = 128) received guideline-based care; however, in addition to standard of care, procalcitonin was measured in the intervention group at days 0, 4, and 7 then weekly. Among these patients, antibiotics were stopped or not started when procalcitonin was below 1.0 ng/mL, but antibiotics were started or continued when procalcitonin was 1.0 ng/mL or more.

The primary outcome was presence or absence of antibiotic use during hospital stay. A range of secondary outcomes were also reported, included all-cause mortality, days of antibiotic use, rates of infection, and endoscopic, radiological, or surgical intervention.

Significantly fewer patients in the procalcitonin group received antibiotics during their stay, compared with the usual-care group (45% vs. 63%), which translated to an adjusted risk difference of –15.6% (P = .0071). Patients in the procalcitonin group who did receive antibiotics received about 1 day less of antibiotic treatment.

Despite the reduced antibiotic usage, length of hospital stay was similar between groups, as were rates of clinical infection, hospital-acquired infection, death, and adverse events, which suggests that the algorithm safely reduced antibiotic usage without negatively impacting clinical outcomes, according to investigators.

“Procalcitonin-based algorithms to guide antibiotic use should be considered in the care of this group of patients and be incorporated into future guidelines on the management of acute pancreatitis,” the investigators concluded.

Aaron Sasson, MD, director of the pancreatic cancer center and codirector of the gastrointestinal oncology team at Stony Brook (N.Y.) Medicine, said the study is noteworthy because it addresses an important topic with a large prospective randomized trial; however, he pointed out some limitations.

“There are several issues with this trial,” Dr. Sasson said in a written comment. “First, it included a large percentage of patients with mild acute pancreatitis, a group of patients for whom the use of antibiotics is not controversial. Secondly, the rate of infected pancreatic necrosis was 5% in both arms of the study, indicating the lack of severity of the cohort of patients.”

Dr. Sasson said that the algorithm “could be useful” to differentiate between inflammation and infection in patients with acute pancreatitis, “but only as an adjunct with other clinical parameters.”

He suggested that the algorithm would offer more utility if it could distinguish between pancreatic necrosis and infected pancreatic necrosis. “Unfortunately, this trial did not answer this question,” he said, noting that a similar trial involving “only patients with severe pancreatitis” would be needed.

The investigators and Dr. Sasson disclosed no competing interests.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

Patients with hepatitis B virus (HBV) infection and HCC tend to live longer if both their HBV and HCC are treated. Liu and colleagues performed a meta-analysis of trials that addressed the question whether the same is true for patients with hepatitis C virus (HCV) infection and HCC treated with either interferon or direct-acting antivirals (DAA). They included 23, mostly retrospective, cohort studies in the final meta-analysis. Recurrence data were available in 18 studies, with 2013 patients receiving DAA therapy, 1091 patients receiving interferon therapy, and 1571 patients receiving no intervention. There was no significant difference in recurrence between the DAA group and the interferon group. The meta-analysis demonstrated that patients with HCV-related HCC treated with DAA had a lower risk for HCC recurrence (adjusted hazard ratio [HR] 0.55, 95% CI 0.41-0.74, P < .001; I² 66.6%, P < .001) and a better overall survival (OS) (adjusted HR 0.36, 95% CI 0.16–0.83, P = .017; I² 90.7%, P < .001) than patients with no intervention. The authors concluded that DAA therapy can prevent recurrence and improve OS of patients with HCV-related HCC, especially if a sustained virologic response is achieved.

Atezolizumab with bevacizumab is the current first-line standard of care for patients with unresectable HCC, offering an improved OS compared to sorafenib, as demonstrated in the phase 3 IMbrave150 study. Alternate combinations, such as atezolizumab and cabozantinib, are also being investigated in this setting. The COSMIC-312 phase 3 randomized controlled trial evaluated 837 patients with unresectable HCC who had not received previous systemic therapy. They were randomly assigned in a 2:1:1 ratio to receive cabozantinib plus atezolizumab (n = 432), sorafenib (n = 217), or single-agent cabozantinib (n = 188). Although the patients receiving atezolizumab + cabozantinib had a significantly longer median progression-free survival (6.8 vs 4.2 months; HR, 0.63; P = .001) than patients who received sorafenib, both groups had a similar median OS (15.4 vs 15.5 months; HR, 0.90; P = .44). The authors concluded that this combination requires more study in this patient population.

For patients with unresectable HCC who are unable to tolerate combination therapy in the first-line setting, single-agent therapy might be an option. Verset and colleagues reported the results of a phase 2 study evaluating pembrolizumab in this setting. Cohort 2 of the KEYNOTE-224 study evaluated 51 systemic therapy–naive patients with unresectable HCC who received pembrolizumab for up to 2 years. After 27 months of median follow-up, the median progression-free survival was 4 months (95% CI 2-8 months) and the OS was 17 months (95% CI 8-23 months). The objective response rate was 16% (95% CI 7%-29%). Grade ≥ 3 treatment-related adverse events were observed in 16% of patients. In this prospective study, pembrolizumab provided durable antitumor activity, a promising OS, and a safety profile consistent with previous observations.

One of the cornerstones of member engagement within the American Gastroenterological Association is its committees, which provide a platform for AGA members to network, effect change at the institutional level, and obtain leadership positions. For many within the AGA, exposure to these committees occurs during training. Both of us were first introduced to the possibility of serving on an AGA committee by faculty members at our institution. Each year, applications for available committee positions open in the fall and are due on Nov. 1. While you can be nominated by other members, self-nomination is common and encouraged. Truthfully, neither of us was quite certain what committee membership would entail. However, we both applied to several committees because we knew that it would be an excellent opportunity to network with leading gastroenterologists across the country and to have the ability to become involved in key AGA programs.

We were selected to serve 2-year terms as trainee members on the Government Affairs and Publication Committees, respectively, which gave us a deeper understanding of how an organization with both a full-time professional staff and group of volunteer members functions. A unique feature of the AGA is its Trainee and Early Career (TEC) Committee, which mainly comprises trainee members who serve on other committees. By virtue of our roles with the other committees, we also became full-fledged members of the TEC committee, which is dedicated to enhancing the experience for trainees and those who are within 5 years of graduation.

One of the most innovative programs developed by the TEC committee is Career Development Workshops, which is a webinar series focused on important topics not covered in fellowship, such as different career paths, personal finance, and how to increase the number of underrepresented individuals in the field. The predecessor of the Career Development Workshops was the in-person Regional Practice Skills Workshop, and we both took on the responsibility of planning and organizing separate workshops. For one of us (Stephanie), that involved enlisting our fellowship program to host the event. For the other (Peter), it meant collaborating with our local gastroenterology society to cosponsor the workshop. It was extremely rewarding to organize the workshops, which allowed us to work closely with AGA staff and local gastroenterology faculty, as well as our peers, to bring the events to fruition. For both of us, the success of the Regional Practice Skills Workshop was one of the highlights of our tenure on the TEC committee.

Applying to become a committee chair follows the same process and timeline as for any other committee position, and you can be nominated or self-nominate. Although previous experience on that specific committee is not a prerequisite for most chair positions, having previously served on any AGA committee or task force is generally required. Successful applicants serve for 1 year as chair-elect, during which they work closely with the outgoing chair and staff to ensure a smooth transition when their 3-year term as chair officially begins in June.

Each committee has a guiding mission statement and a staff liaison who provides institutional knowledge and logistical support. However, the committee members, and especially the chair, have considerable latitude to develop and implement new initiatives or retire old ones. The entire committee meets twice per year, once in September in Washington, D.C., and once at DDW. Between the meetings, working groups are formed to move the various programs forward. In addition to the Career Development Workshops, the TEC committee organizes the Young Delegates program (which allows any AGA member to volunteer on small, time-limited projects), a symposium at DDW focused on trainee and early career issues, and a networking event at DDW. Moreover, we collaborate with other committees and provide input from the perspective of younger members on larger initiatives such as the AGA Equity Project and Career Compass.

As chair, we lead the twice-yearly meetings as well as the working groups. We strongly encourage all committee members to participate on at least one working group, which develops leadership skills and provides the opportunity to moderate sessions for the Career Development Workshops and DDW symposium. Moreover, we solicit feedback on ways to improve current programming, start new initiatives, and work with other committees that the TEC committee members are part of. Trainees and early career members are seen as a key constituency group within the AGA, and we take the responsibility of increasing the value of membership for this group seriously.

As early-career physicians ourselves, we also view the chance to serve as a committee chair as a great career development opportunity. It allows us to expand our professional networks, help shape an organization that is a leading voice and advocate for digestive health, and meet the needs of young members who are the future of the AGA.

There is no doubt that all of you have achieved amazing things on the way to becoming a trainee or early career professional in the competitive fields of gastroenterology and hepatology. The AGA is constantly looking for bright, motivated individuals to serve as volunteers and future leaders. Our experience shows that with a bit of persistence to get in the door – through Young Delegates or a committee – along with lots of hard work along the way, you will be in a great position to rise through the ranks and help lead an organization at the vanguard of our field.

Dr. Liang is assistant professor of medicine and population health, New York University Langone Health, and a staff physician at VA New York Harbor Health Care System. Dr. Pointer is a founder and managing partner of Digestive and Liver Health Specialists. She is on staff as a clinical gastroenterologist at Tristar Hendersonville (Tenn.) Medical Center. They have no conflicts of interest.

One of the cornerstones of member engagement within the American Gastroenterological Association is its committees, which provide a platform for AGA members to network, effect change at the institutional level, and obtain leadership positions. For many within the AGA, exposure to these committees occurs during training. Both of us were first introduced to the possibility of serving on an AGA committee by faculty members at our institution. Each year, applications for available committee positions open in the fall and are due on Nov. 1. While you can be nominated by other members, self-nomination is common and encouraged. Truthfully, neither of us was quite certain what committee membership would entail. However, we both applied to several committees because we knew that it would be an excellent opportunity to network with leading gastroenterologists across the country and to have the ability to become involved in key AGA programs.

We were selected to serve 2-year terms as trainee members on the Government Affairs and Publication Committees, respectively, which gave us a deeper understanding of how an organization with both a full-time professional staff and group of volunteer members functions. A unique feature of the AGA is its Trainee and Early Career (TEC) Committee, which mainly comprises trainee members who serve on other committees. By virtue of our roles with the other committees, we also became full-fledged members of the TEC committee, which is dedicated to enhancing the experience for trainees and those who are within 5 years of graduation.

One of the most innovative programs developed by the TEC committee is Career Development Workshops, which is a webinar series focused on important topics not covered in fellowship, such as different career paths, personal finance, and how to increase the number of underrepresented individuals in the field. The predecessor of the Career Development Workshops was the in-person Regional Practice Skills Workshop, and we both took on the responsibility of planning and organizing separate workshops. For one of us (Stephanie), that involved enlisting our fellowship program to host the event. For the other (Peter), it meant collaborating with our local gastroenterology society to cosponsor the workshop. It was extremely rewarding to organize the workshops, which allowed us to work closely with AGA staff and local gastroenterology faculty, as well as our peers, to bring the events to fruition. For both of us, the success of the Regional Practice Skills Workshop was one of the highlights of our tenure on the TEC committee.

Applying to become a committee chair follows the same process and timeline as for any other committee position, and you can be nominated or self-nominate. Although previous experience on that specific committee is not a prerequisite for most chair positions, having previously served on any AGA committee or task force is generally required. Successful applicants serve for 1 year as chair-elect, during which they work closely with the outgoing chair and staff to ensure a smooth transition when their 3-year term as chair officially begins in June.

Each committee has a guiding mission statement and a staff liaison who provides institutional knowledge and logistical support. However, the committee members, and especially the chair, have considerable latitude to develop and implement new initiatives or retire old ones. The entire committee meets twice per year, once in September in Washington, D.C., and once at DDW. Between the meetings, working groups are formed to move the various programs forward. In addition to the Career Development Workshops, the TEC committee organizes the Young Delegates program (which allows any AGA member to volunteer on small, time-limited projects), a symposium at DDW focused on trainee and early career issues, and a networking event at DDW. Moreover, we collaborate with other committees and provide input from the perspective of younger members on larger initiatives such as the AGA Equity Project and Career Compass.

As chair, we lead the twice-yearly meetings as well as the working groups. We strongly encourage all committee members to participate on at least one working group, which develops leadership skills and provides the opportunity to moderate sessions for the Career Development Workshops and DDW symposium. Moreover, we solicit feedback on ways to improve current programming, start new initiatives, and work with other committees that the TEC committee members are part of. Trainees and early career members are seen as a key constituency group within the AGA, and we take the responsibility of increasing the value of membership for this group seriously.

As early-career physicians ourselves, we also view the chance to serve as a committee chair as a great career development opportunity. It allows us to expand our professional networks, help shape an organization that is a leading voice and advocate for digestive health, and meet the needs of young members who are the future of the AGA.

There is no doubt that all of you have achieved amazing things on the way to becoming a trainee or early career professional in the competitive fields of gastroenterology and hepatology. The AGA is constantly looking for bright, motivated individuals to serve as volunteers and future leaders. Our experience shows that with a bit of persistence to get in the door – through Young Delegates or a committee – along with lots of hard work along the way, you will be in a great position to rise through the ranks and help lead an organization at the vanguard of our field.

Dr. Liang is assistant professor of medicine and population health, New York University Langone Health, and a staff physician at VA New York Harbor Health Care System. Dr. Pointer is a founder and managing partner of Digestive and Liver Health Specialists. She is on staff as a clinical gastroenterologist at Tristar Hendersonville (Tenn.) Medical Center. They have no conflicts of interest.

One of the cornerstones of member engagement within the American Gastroenterological Association is its committees, which provide a platform for AGA members to network, effect change at the institutional level, and obtain leadership positions. For many within the AGA, exposure to these committees occurs during training. Both of us were first introduced to the possibility of serving on an AGA committee by faculty members at our institution. Each year, applications for available committee positions open in the fall and are due on Nov. 1. While you can be nominated by other members, self-nomination is common and encouraged. Truthfully, neither of us was quite certain what committee membership would entail. However, we both applied to several committees because we knew that it would be an excellent opportunity to network with leading gastroenterologists across the country and to have the ability to become involved in key AGA programs.

We were selected to serve 2-year terms as trainee members on the Government Affairs and Publication Committees, respectively, which gave us a deeper understanding of how an organization with both a full-time professional staff and group of volunteer members functions. A unique feature of the AGA is its Trainee and Early Career (TEC) Committee, which mainly comprises trainee members who serve on other committees. By virtue of our roles with the other committees, we also became full-fledged members of the TEC committee, which is dedicated to enhancing the experience for trainees and those who are within 5 years of graduation.

One of the most innovative programs developed by the TEC committee is Career Development Workshops, which is a webinar series focused on important topics not covered in fellowship, such as different career paths, personal finance, and how to increase the number of underrepresented individuals in the field. The predecessor of the Career Development Workshops was the in-person Regional Practice Skills Workshop, and we both took on the responsibility of planning and organizing separate workshops. For one of us (Stephanie), that involved enlisting our fellowship program to host the event. For the other (Peter), it meant collaborating with our local gastroenterology society to cosponsor the workshop. It was extremely rewarding to organize the workshops, which allowed us to work closely with AGA staff and local gastroenterology faculty, as well as our peers, to bring the events to fruition. For both of us, the success of the Regional Practice Skills Workshop was one of the highlights of our tenure on the TEC committee.

Applying to become a committee chair follows the same process and timeline as for any other committee position, and you can be nominated or self-nominate. Although previous experience on that specific committee is not a prerequisite for most chair positions, having previously served on any AGA committee or task force is generally required. Successful applicants serve for 1 year as chair-elect, during which they work closely with the outgoing chair and staff to ensure a smooth transition when their 3-year term as chair officially begins in June.

Each committee has a guiding mission statement and a staff liaison who provides institutional knowledge and logistical support. However, the committee members, and especially the chair, have considerable latitude to develop and implement new initiatives or retire old ones. The entire committee meets twice per year, once in September in Washington, D.C., and once at DDW. Between the meetings, working groups are formed to move the various programs forward. In addition to the Career Development Workshops, the TEC committee organizes the Young Delegates program (which allows any AGA member to volunteer on small, time-limited projects), a symposium at DDW focused on trainee and early career issues, and a networking event at DDW. Moreover, we collaborate with other committees and provide input from the perspective of younger members on larger initiatives such as the AGA Equity Project and Career Compass.

As chair, we lead the twice-yearly meetings as well as the working groups. We strongly encourage all committee members to participate on at least one working group, which develops leadership skills and provides the opportunity to moderate sessions for the Career Development Workshops and DDW symposium. Moreover, we solicit feedback on ways to improve current programming, start new initiatives, and work with other committees that the TEC committee members are part of. Trainees and early career members are seen as a key constituency group within the AGA, and we take the responsibility of increasing the value of membership for this group seriously.

As early-career physicians ourselves, we also view the chance to serve as a committee chair as a great career development opportunity. It allows us to expand our professional networks, help shape an organization that is a leading voice and advocate for digestive health, and meet the needs of young members who are the future of the AGA.

There is no doubt that all of you have achieved amazing things on the way to becoming a trainee or early career professional in the competitive fields of gastroenterology and hepatology. The AGA is constantly looking for bright, motivated individuals to serve as volunteers and future leaders. Our experience shows that with a bit of persistence to get in the door – through Young Delegates or a committee – along with lots of hard work along the way, you will be in a great position to rise through the ranks and help lead an organization at the vanguard of our field.

Dr. Liang is assistant professor of medicine and population health, New York University Langone Health, and a staff physician at VA New York Harbor Health Care System. Dr. Pointer is a founder and managing partner of Digestive and Liver Health Specialists. She is on staff as a clinical gastroenterologist at Tristar Hendersonville (Tenn.) Medical Center. They have no conflicts of interest.

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Psittacosis, a rare disease, has been underdiagnosed or misdiagnosed during the COVID-19 pandemic, likely because the symptoms of the disease are similar to COVID-19 symptoms, researchers suggest on the basis of data from 32 individuals.

Diagnosis of and screening for COVID-19 continues to increase; however, cases of atypical pneumonia caused by uncommon pathogens, which presents with similar symptoms, may be missed, wrote Qiaoqiao Yin, MS, of Zhejiang Provincial People’s Hospital, China, and colleagues.

“The clinical manifestations of human psittacosis can present as rapidly progressing severe pneumonia, acute respiratory distress syndrome, sepsis, and multiple organ failure,” but human cases have not been well studied, they say.

In a study  published in the International Journal of Infectious Diseases, the researchers reviewed data from 32 adults diagnosed with Chlamydia psittaci pneumonia during the COVID-19 pandemic between April 2020 and June 2021 in China. The median age of the patients was 63 years, 20 were men, and 20 had underlying diseases.

A total of 17 patients presented with fever, cough, and expectoration of yellow-white sputum. At the time of hospital admission, three patients had myalgia, two had headache, and two had hypertension. The patients were originally suspected of having COVID-19.

“All patients showed atypical pneumonia, including inflammatory infiltration, pleural effusion, multiple inflammatory exudative lesions with interstitial edema, lung abscesses, and white lung,” all of which could be observed in COVID-19 patients as well, the researchers wrote.

Reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) testing were used to rule out COVID-19. The researchers then used metagenomic next-generation sequencing (mNGS) to identify the disease-causing pathogens. They collected 18 bronchoalveolar lavage fluid (BALF) samples, 9 peripheral blood samples, and 5 sputum samples. The mNGS identified C. psittaci as the suspected pathogen within 48 hours. Suspected C. psittaci infections were confirmed by endpoint PCR for the BALF and sputum samples and six of nine blood samples, “indicating a lower sensitivity of PCR compared to mNGS for blood samples,” the researchers say. No other potential pathogens were identified.

Psittacosis is common in birds but is rare in humans. C. psittaci is responsible for 1%-8% of cases involving community-acquired pneumonia in China, the researchers note. Although poultry is a source of infection, 25 of the patients in the study did not report a history of exposure to poultry or pigeons at the time of their initial hospital admission. Many patients may be unaware of exposures to poultry, which further complicates the C. psittaci diagnosis, they note.

All patients were treated with doxycycline-based regimens and showed improvement.

The findings were limited by several factors, including the lack of a definitive diagnostic tool for C. psittaci and the lack of convalescent serum samples to confirm cases, the researchers note. In addition, molecular detections for PCR are unavailable in most hospitals in China, they say. The results represent the largest known collection of suspected C. psittaci pneumonia cases and highlight the need for clinician vigilance and awareness of this rare condition, especially in light of the potential for misdiagnosis during the ongoing COVID-19 pandemic, they conclude.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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