CHEST Physician

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Advances in genetic testing and newly discovered biomarkers can help screen newborns and monitor inflammation and pulmonary exacerbations in patients diagnosed with cystic fibrosis.

At the European Respiratory Society (ERS) 2024 International Congress, clinical researchers presented results from the Turkish context.

Cystic fibrosis is the most common genetic disorder among Caucasians. The average prevalence at birth in Europe is 1 in 5000, whereas the overall population averages 1 in 9000. Both rates vary significantly based on geographic area. In the central Anatolia region, one study found that the incidence of cystic fibrosis is 1 in 3400 live births.

Çigdem Korkmaz, a researcher at the Department of Pediatric Pulmonology at the Istanbul University-Cerrahpasa in Istanbul, Turkey, said that diagnosis in Turkey is especially challenging because of the genetic diversity of cystic fibrosis within the population. She said genetic testing might be necessary to catch missed cases by traditional screening methods.
 

Genetic Testing Picks Up Missed Cases

In 2022, 30 European countries run newborn bloodspot screening for cystic fibrosis, with 26 national programs. Screening protocols vary between countries but generally involve initial screening using an immunoreactive trypsinogen (IRT) blood test. Follow-up testing may include a second IRT test, DNA analysis for common CFTR mutations, and sweat chloride test (SCT).

Turkey introduced newborn screening for cystic fibrosis in 2015. Newborns with an elevated IRT and confirmatory SCT undergo genetic testing. However, in a retrospective study, researchers found that IRT tests turn many false-positive results, and some patients who turn a normal SCT are diagnosed with the disease through genetic testing.

The study included 205 infants referred to a tertiary care center in Istanbul between January 2015 and January 2023 following an elevator IRT result. The researchers analyzed the clinical and sociodemographic data, IRT and SCT values, and genetic analysis results.

They found that cystic fibrosis was confirmed in only 30% newborns, while genetic testing could identify nine cases otherwise missed by SCT. “The high false-positive rate of the current screening strategy suggests that the IRT thresholds used in Turkey may be too low,” said Ms. Korkmaz, who presented the study at the ERS Congress. She added that genetic testing might be important, especially in patients with normal SCT results. “Early diagnosis means these patients avoid missing or delaying treatments.”
 

Biomarkers for Monitoring Cystic Fibrosis Exacerbations

C-reactive protein (CRP) blood testing is typically used in monitoring inflammation and pulmonary exacerbations in patients who have already been diagnosed with cystic fibrosis. CRP is an inflammatory biomarker that increases in patients with cystic fibrosis during pulmonary exacerbations and settles with treatment.

Researchers at Gazi University in Ankara, Turkey, found other biomarkers to identify inflammation and pulmonary exacerbations with great sensitivity and specificity in patients with cystic fibrosis.

Over 3 years, from 2021 to 2024, the researchers analyzed blood samples from 54 children aged 1-18 years during exacerbation and non-exacerbation periods. Besides CRP, they tested CRP/albumin (ALB) ratio, neutrophil-to-lymphocyte ratio (NLR), delivered NLR (dNLR), and systemic immune inflammation (SII).

All biomarkers increased during exacerbation episodes. All showed high specificity and sensitivity:

• CPR/ALB had a specificity of 81% and a sensitivity of 90% at a cutoff of 1.7 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• NLR had a specificity of 62% and a sensitivity of 79% at a cutoff of 2.2 mg/dL.
• SII had a specificity of 86% and a sensitivity of 67% at a cutoff of 426 mg/dL.
• dNLR had a specificity of 71% and a sensitivity of 66% at a cutoff of 1.15 mg/dL.
• In comparison, CPR had a specificity of 85% and a sensitivity of 84% at a cutoff of 6.2 mg/dL.

Ayse Tana Aslan, a professor at the Department of Pediatric Pulmonology, Faculty of Medicine, at Gazi University in Ankara, Turkey, who presented the results at the ERS Congress, said that these biomarkers can be easily and quickly identified with a blood test while waiting on phlegm culture results, which can take days. “It is important to predict inflammation and exacerbation quickly so that patients can start a course of antibiotics as soon as possible,” she said.

Ms. Korkmaz and Ms. Aslan reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments. More objective tests like blood eosinophil counts are needed for early diagnosis and to avoid unnecessary medication use in children unlikely to develop asthma.

Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.

Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.

“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
 

Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness 

In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”

Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.

Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.

Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.

“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
 

How to Treat Those Who Don’t Have Eosinophilia

Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.

Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.

Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.

Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”

Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments. More objective tests like blood eosinophil counts are needed for early diagnosis and to avoid unnecessary medication use in children unlikely to develop asthma.

Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.

Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.

“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
 

Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness 

In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”

Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.

Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.

Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.

“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
 

How to Treat Those Who Don’t Have Eosinophilia

Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.

Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.

Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.

Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”

Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VIENNA — Simply relying on clinical symptoms is insufficient to predict which children with wheezing will develop asthma and respond to treatments. More objective tests like blood eosinophil counts are needed for early diagnosis and to avoid unnecessary medication use in children unlikely to develop asthma.

Sejal Saglani, MD, PhD, a professor of pediatric respiratory medicine at the National Heart and Lung Institute, Imperial College, London, England, said that preschool wheezing has long-term adverse consequences through to adulthood. “We need to prevent that downward trajectory of low lung function,” she said, presenting the latest research in the field at the annual European Respiratory Society International Congress.

Wheezing affects up to one third of all infants and preschool children, with one third developing asthma later in life. “It’s important to identify those kids because then we can treat them with the right medication,” said Mariëlle W.H. Pijnenburg, MD, PhD, a pulmonary specialist at Erasmus University Rotterdam in the Netherlands.

“We cannot just use clinical phenotype to decide what treatment a child should get. We need to run tests to identify the endotype of preschool wheeze and intervene appropriately,” Dr. Saglani added.
 

Eosinophilia as a Biomarker for Predicting Exacerbations and Steroid Responsiveness 

In a cluster analysis, Dr. Saglani and colleagues classified preschool children with wheezing into two main subgroups: Those who experience frequent exacerbations and those who experience sporadic attacks. Frequent exacerbators were more likely to develop asthma, use asthma medications, and show signs of reduced lung function and airway inflammation, such as higher fractional exhaled nitric oxide and allergic sensitization. “Severe and frequent exacerbators are the kids that get in trouble,” she said. “They’re the ones we must identify at preschool age and really try to minimize their exacerbations.”

Research has shown that eosinophilia is a valuable biomarker in predicting both asthma exacerbations and responsiveness to inhaled corticosteroids. Children with elevated blood eosinophils are more likely to experience frequent and severe exacerbations. These children often demonstrate an inflammatory profile more responsive to corticosteroids, making eosinophilia a predictor of treatment success. Children with eosinophilia are also more likely to have underlying allergic sensitizations, which further supports the use of corticosteroids as part of their management strategy.

Dr. Saglani said a simple blood test can provide a window into the child’s inflammatory status, allowing physicians to make more targeted and personalized treatment plans.

Traditionally, identifying eosinophilia required venipuncture and laboratory analysis, which can be time consuming and impractical in a busy clinical setting. Dr. Saglani’s research group is developing a point-of-care test designed to quickly and efficiently measure blood eosinophil levels in children with asthma or wheezing symptoms from a finger-prick test. Preliminary data presented at the congress show that children with higher eosinophil counts in the clinic were more likely to experience an asthma attack within 3 months.

“The problem is the majority of the children we see are either not atopic or do not have high blood eosinophils. What are we going to do with those?”
 

How to Treat Those Who Don’t Have Eosinophilia

Most children with wheezing are not atopic and do not exhibit eosinophilic inflammation, and these children may not respond as effectively to corticosteroids. How to treat them remains the “1-billion-dollar question,” Dr. Saglani said.

Respiratory syncytial virus and rhinovirus play a crucial role in triggering wheezing episodes in these children. Research has shown that viral-induced wheezing is a common feature in this phenotype, and repeated viral infections can lead to an increased severity and frequency of exacerbations. However, there are currently no effective antiviral therapies or vaccines for rhinovirus, which limits the ability to address the viral component of the disease directly.

Up to 50% of children with severe, recurrent wheezing also have bacterial pathogens like Moraxella catarrhalis and Haemophilus influenzae in their lower airways. For these children, addressing the bacterial infection is the best treatment option to mitigate the wheezing. “We now have something that we can target with antibiotics for those who don’t respond to corticosteroids,” Dr. Saglani said.

Dr. Pijnenburg said that this body of research is helping pulmonary specialists and general pediatricians navigate the complexity of childhood wheezing beyond phenotyping and symptoms. “We need to dive more deeply into those kids with preschool wheezing to see what’s happening in their lungs.”

Dr. Pijnenburg and Dr. Saglani reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

New COVID-19 vaccines formulated for better protection against the currently circulating variants have been approved by the US Food and Drug Administration.

The COVID vaccines available this fall have been updated to better match the currently circulating COVID strains, said William Schaffner, MD, professor of medicine in the Division of Infectious Diseases at Vanderbilt University, Nashville, Tennessee, in an interview.

“The Pfizer and Moderna vaccines — both mRNA vaccines — target the KP.2 variant, while the Novavax vaccine targets the JN.1 variant, which is a predecessor to KP.2,” said Dr. Schaffner, who also serves as a spokesperson for the National Foundation for Infectious Diseases. “The Novavax vaccine is a protein adjuvant vaccine made in a more traditional fashion and may appeal to those who remain hesitant about receiving an mRNA vaccine,” he explained. However, all three vaccines are designed to protect against severe COVID illness and reduce the likelihood of hospitalization, he said.
 

Who Needs It?

“The CDC’s Advisory Committee on Immunization Practices (ACIP) continues to recommend that everyone in the United States who is age 6 months and older receive the updated COVID vaccine this fall, along with influenza vaccine,” Dr. Schaffner said.

“This was not a surprise because COVID will produce a sizable winter outbreak,” he predicted. Although older people and those who have chronic medical conditions such as heart or lung disease, diabetes, or other immunocompromising conditions suffer the most serious impact of COVID, he said. “The virus can strike anyone, even the young and healthy.” The risk for long COVID persists as well, he pointed out.

The ACIP recommendation is endorsed by the American Academy of Pediatrics and other professional organizations, Dr. Shaffner said.

A frequently asked question is whether the COVID and flu vaccines can be given at the same time, and the answer is yes, according to a statement from the Centers for Disease Control and Prevention (CDC).

“The optimal time to be vaccinated is late September and anytime during October in order to get the benefit of protection through the winter,” Dr. Schaffner said.

As with earlier versions of the COVID-19 vaccine, side effects vary from person to person. Reported side effects of the updated vaccine are similar to those seen with earlier versions and may include injection site pain, redness and swelling, fatigue, headache, muscle pain, chills, nausea, and fever, but most of these are short-lived, according to the CDC.
 

Clinical Guidance

The CDC’s clinical guidance for COVID-19 vaccination outlines more specific guidance for vaccination based on age, vaccination history, and immunocompromised status and will be updated as needed.

A notable difference in the latest guidance is the recommendation of only one shot for adults aged 65 years and older who are NOT moderately or severely immunocompromised. For those who are moderately or severely immunocompromised, the CDC recommends two to three doses of the same brand of vaccine.

Dr. Schaffner strongly encouraged clinicians to recommend the COVID-19 vaccination for all eligible patients. “COVID is a nasty virus that can cause serious disease in anyone,” and protection from previous vaccination or prior infection has likely waned, he said.

Dr. Schaffner also encouraged healthcare professionals and their families to lead by example. “We should all be vaccinated and let our patients know that we are vaccinated and that we want all our patents to be protected,” he said.

The updated COVID-19 vaccination recommendations have become much simpler for clinicians and patients, with a single messenger RNA (mRNA) vaccine required for anyone older than 5 years, said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

“The recommendations are a bit more complex for children under 5 years old receiving their first vaccination; they require two to three doses depending on the brand,” he said. “It is important to review the latest recommendations to plan the doses with the correct interval timing. Considering the doses may be 3-4 weeks apart, start early,” he advised.
 

One-Time Dosing

Although the updated mRNA vaccine is currently recommended as a one-time dose, Dr. Cennimo said he can envision a scenario later in the season when a second dose is recommended for the elderly and those at high risk for severe illness. Dr. Cennimo said that he strongly agrees with the recommendations that everyone aged 6 months and older receive an updated COVID-19 vaccine. Older age remains the prime risk factor, but anyone can become infected, he said.

Predicting a prime time to get vaccinated is tricky because no one knows when the expected rise in winter cases will occur, said Dr. Cennimo.

“We know from years of flu vaccine data that some number of people who delay the vaccine will never return and will miss protection,” he said. Therefore, delaying vaccination is not recommended. Dr. Cennimo plans to follow his habit of getting vaccinated in early October. “I anticipate the maximal effectiveness of the vaccine will carry me through the winter,” he said.

Data support the safety and effectiveness for both flu and COVID vaccines if they are given together, and some research on earlier versions of COVID vaccines suggested that receiving flu and COVID vaccines together might increase the antibody response against COVID, but similar studies of the updated version have not been done, Dr. Cennimo said.

Clinicians may have to overcome the barrier of COVID fatigue to encourage vaccination, Dr. Cennimo said. Many people say they “want it to be over,” he said, but SARS-CoV-2, established as a viral respiratory infection, shows no signs of disappearing. In addition, new data continue to show higher mortality associated with COVID-19 than with influenza, he said.

“We need to explain to our patients that COVID-19 is still here and is still dangerous. The yearly influenza vaccination campaigns should have established and normalized the idea of an updated vaccine targeted for the season’s predicated strains is expected,” he emphasized. “We now have years of safety data behind these vaccines, and we need to make a strong recommendation for this protection,” he said.

COVID-19 vaccines are covered by private insurance, as well as by Medicare and Medicaid, according to the CDC. Vaccination for uninsured children is covered through the Vaccines for Children Program.

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

New COVID-19 vaccines formulated for better protection against the currently circulating variants have been approved by the US Food and Drug Administration.

The COVID vaccines available this fall have been updated to better match the currently circulating COVID strains, said William Schaffner, MD, professor of medicine in the Division of Infectious Diseases at Vanderbilt University, Nashville, Tennessee, in an interview.

“The Pfizer and Moderna vaccines — both mRNA vaccines — target the KP.2 variant, while the Novavax vaccine targets the JN.1 variant, which is a predecessor to KP.2,” said Dr. Schaffner, who also serves as a spokesperson for the National Foundation for Infectious Diseases. “The Novavax vaccine is a protein adjuvant vaccine made in a more traditional fashion and may appeal to those who remain hesitant about receiving an mRNA vaccine,” he explained. However, all three vaccines are designed to protect against severe COVID illness and reduce the likelihood of hospitalization, he said.
 

Who Needs It?

“The CDC’s Advisory Committee on Immunization Practices (ACIP) continues to recommend that everyone in the United States who is age 6 months and older receive the updated COVID vaccine this fall, along with influenza vaccine,” Dr. Schaffner said.

“This was not a surprise because COVID will produce a sizable winter outbreak,” he predicted. Although older people and those who have chronic medical conditions such as heart or lung disease, diabetes, or other immunocompromising conditions suffer the most serious impact of COVID, he said. “The virus can strike anyone, even the young and healthy.” The risk for long COVID persists as well, he pointed out.

The ACIP recommendation is endorsed by the American Academy of Pediatrics and other professional organizations, Dr. Shaffner said.

A frequently asked question is whether the COVID and flu vaccines can be given at the same time, and the answer is yes, according to a statement from the Centers for Disease Control and Prevention (CDC).

“The optimal time to be vaccinated is late September and anytime during October in order to get the benefit of protection through the winter,” Dr. Schaffner said.

As with earlier versions of the COVID-19 vaccine, side effects vary from person to person. Reported side effects of the updated vaccine are similar to those seen with earlier versions and may include injection site pain, redness and swelling, fatigue, headache, muscle pain, chills, nausea, and fever, but most of these are short-lived, according to the CDC.
 

Clinical Guidance

The CDC’s clinical guidance for COVID-19 vaccination outlines more specific guidance for vaccination based on age, vaccination history, and immunocompromised status and will be updated as needed.

A notable difference in the latest guidance is the recommendation of only one shot for adults aged 65 years and older who are NOT moderately or severely immunocompromised. For those who are moderately or severely immunocompromised, the CDC recommends two to three doses of the same brand of vaccine.

Dr. Schaffner strongly encouraged clinicians to recommend the COVID-19 vaccination for all eligible patients. “COVID is a nasty virus that can cause serious disease in anyone,” and protection from previous vaccination or prior infection has likely waned, he said.

Dr. Schaffner also encouraged healthcare professionals and their families to lead by example. “We should all be vaccinated and let our patients know that we are vaccinated and that we want all our patents to be protected,” he said.

The updated COVID-19 vaccination recommendations have become much simpler for clinicians and patients, with a single messenger RNA (mRNA) vaccine required for anyone older than 5 years, said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

“The recommendations are a bit more complex for children under 5 years old receiving their first vaccination; they require two to three doses depending on the brand,” he said. “It is important to review the latest recommendations to plan the doses with the correct interval timing. Considering the doses may be 3-4 weeks apart, start early,” he advised.
 

One-Time Dosing

Although the updated mRNA vaccine is currently recommended as a one-time dose, Dr. Cennimo said he can envision a scenario later in the season when a second dose is recommended for the elderly and those at high risk for severe illness. Dr. Cennimo said that he strongly agrees with the recommendations that everyone aged 6 months and older receive an updated COVID-19 vaccine. Older age remains the prime risk factor, but anyone can become infected, he said.

Predicting a prime time to get vaccinated is tricky because no one knows when the expected rise in winter cases will occur, said Dr. Cennimo.

“We know from years of flu vaccine data that some number of people who delay the vaccine will never return and will miss protection,” he said. Therefore, delaying vaccination is not recommended. Dr. Cennimo plans to follow his habit of getting vaccinated in early October. “I anticipate the maximal effectiveness of the vaccine will carry me through the winter,” he said.

Data support the safety and effectiveness for both flu and COVID vaccines if they are given together, and some research on earlier versions of COVID vaccines suggested that receiving flu and COVID vaccines together might increase the antibody response against COVID, but similar studies of the updated version have not been done, Dr. Cennimo said.

Clinicians may have to overcome the barrier of COVID fatigue to encourage vaccination, Dr. Cennimo said. Many people say they “want it to be over,” he said, but SARS-CoV-2, established as a viral respiratory infection, shows no signs of disappearing. In addition, new data continue to show higher mortality associated with COVID-19 than with influenza, he said.

“We need to explain to our patients that COVID-19 is still here and is still dangerous. The yearly influenza vaccination campaigns should have established and normalized the idea of an updated vaccine targeted for the season’s predicated strains is expected,” he emphasized. “We now have years of safety data behind these vaccines, and we need to make a strong recommendation for this protection,” he said.

COVID-19 vaccines are covered by private insurance, as well as by Medicare and Medicaid, according to the CDC. Vaccination for uninsured children is covered through the Vaccines for Children Program.

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

New COVID-19 vaccines formulated for better protection against the currently circulating variants have been approved by the US Food and Drug Administration.

The COVID vaccines available this fall have been updated to better match the currently circulating COVID strains, said William Schaffner, MD, professor of medicine in the Division of Infectious Diseases at Vanderbilt University, Nashville, Tennessee, in an interview.

“The Pfizer and Moderna vaccines — both mRNA vaccines — target the KP.2 variant, while the Novavax vaccine targets the JN.1 variant, which is a predecessor to KP.2,” said Dr. Schaffner, who also serves as a spokesperson for the National Foundation for Infectious Diseases. “The Novavax vaccine is a protein adjuvant vaccine made in a more traditional fashion and may appeal to those who remain hesitant about receiving an mRNA vaccine,” he explained. However, all three vaccines are designed to protect against severe COVID illness and reduce the likelihood of hospitalization, he said.
 

Who Needs It?

“The CDC’s Advisory Committee on Immunization Practices (ACIP) continues to recommend that everyone in the United States who is age 6 months and older receive the updated COVID vaccine this fall, along with influenza vaccine,” Dr. Schaffner said.

“This was not a surprise because COVID will produce a sizable winter outbreak,” he predicted. Although older people and those who have chronic medical conditions such as heart or lung disease, diabetes, or other immunocompromising conditions suffer the most serious impact of COVID, he said. “The virus can strike anyone, even the young and healthy.” The risk for long COVID persists as well, he pointed out.

The ACIP recommendation is endorsed by the American Academy of Pediatrics and other professional organizations, Dr. Shaffner said.

A frequently asked question is whether the COVID and flu vaccines can be given at the same time, and the answer is yes, according to a statement from the Centers for Disease Control and Prevention (CDC).

“The optimal time to be vaccinated is late September and anytime during October in order to get the benefit of protection through the winter,” Dr. Schaffner said.

As with earlier versions of the COVID-19 vaccine, side effects vary from person to person. Reported side effects of the updated vaccine are similar to those seen with earlier versions and may include injection site pain, redness and swelling, fatigue, headache, muscle pain, chills, nausea, and fever, but most of these are short-lived, according to the CDC.
 

Clinical Guidance

The CDC’s clinical guidance for COVID-19 vaccination outlines more specific guidance for vaccination based on age, vaccination history, and immunocompromised status and will be updated as needed.

A notable difference in the latest guidance is the recommendation of only one shot for adults aged 65 years and older who are NOT moderately or severely immunocompromised. For those who are moderately or severely immunocompromised, the CDC recommends two to three doses of the same brand of vaccine.

Dr. Schaffner strongly encouraged clinicians to recommend the COVID-19 vaccination for all eligible patients. “COVID is a nasty virus that can cause serious disease in anyone,” and protection from previous vaccination or prior infection has likely waned, he said.

Dr. Schaffner also encouraged healthcare professionals and their families to lead by example. “We should all be vaccinated and let our patients know that we are vaccinated and that we want all our patents to be protected,” he said.

The updated COVID-19 vaccination recommendations have become much simpler for clinicians and patients, with a single messenger RNA (mRNA) vaccine required for anyone older than 5 years, said David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, in an interview.

“The recommendations are a bit more complex for children under 5 years old receiving their first vaccination; they require two to three doses depending on the brand,” he said. “It is important to review the latest recommendations to plan the doses with the correct interval timing. Considering the doses may be 3-4 weeks apart, start early,” he advised.
 

One-Time Dosing

Although the updated mRNA vaccine is currently recommended as a one-time dose, Dr. Cennimo said he can envision a scenario later in the season when a second dose is recommended for the elderly and those at high risk for severe illness. Dr. Cennimo said that he strongly agrees with the recommendations that everyone aged 6 months and older receive an updated COVID-19 vaccine. Older age remains the prime risk factor, but anyone can become infected, he said.

Predicting a prime time to get vaccinated is tricky because no one knows when the expected rise in winter cases will occur, said Dr. Cennimo.

“We know from years of flu vaccine data that some number of people who delay the vaccine will never return and will miss protection,” he said. Therefore, delaying vaccination is not recommended. Dr. Cennimo plans to follow his habit of getting vaccinated in early October. “I anticipate the maximal effectiveness of the vaccine will carry me through the winter,” he said.

Data support the safety and effectiveness for both flu and COVID vaccines if they are given together, and some research on earlier versions of COVID vaccines suggested that receiving flu and COVID vaccines together might increase the antibody response against COVID, but similar studies of the updated version have not been done, Dr. Cennimo said.

Clinicians may have to overcome the barrier of COVID fatigue to encourage vaccination, Dr. Cennimo said. Many people say they “want it to be over,” he said, but SARS-CoV-2, established as a viral respiratory infection, shows no signs of disappearing. In addition, new data continue to show higher mortality associated with COVID-19 than with influenza, he said.

“We need to explain to our patients that COVID-19 is still here and is still dangerous. The yearly influenza vaccination campaigns should have established and normalized the idea of an updated vaccine targeted for the season’s predicated strains is expected,” he emphasized. “We now have years of safety data behind these vaccines, and we need to make a strong recommendation for this protection,” he said.

COVID-19 vaccines are covered by private insurance, as well as by Medicare and Medicaid, according to the CDC. Vaccination for uninsured children is covered through the Vaccines for Children Program.

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

VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.

With over 600 AI-enabled medical devices registered with the US Food and Drug Administration (FDA) since 2020, AI is rapidly pervading healthcare systems. But like any other medical device, AI tools must be thoroughly assessed and follow strict regulations.

Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.

“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization. 

Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
 

The Pros

Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences. 

One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.

Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes. 

AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.

AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
 

The Cons

Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.

For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.

AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.

Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
 

AI’s Black Box

AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making. 

While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.

This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said. 

She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.

“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”

Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.

With over 600 AI-enabled medical devices registered with the US Food and Drug Administration (FDA) since 2020, AI is rapidly pervading healthcare systems. But like any other medical device, AI tools must be thoroughly assessed and follow strict regulations.

Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.

“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization. 

Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
 

The Pros

Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences. 

One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.

Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes. 

AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.

AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
 

The Cons

Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.

For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.

AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.

Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
 

AI’s Black Box

AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making. 

While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.

This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said. 

She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.

“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”

Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — At the European Respiratory Society (ERS) 2024 Congress, experts discussed the benefits and risks of artificial intelligence (AI) in medicine and explored ethical implications and practical challenges.

With over 600 AI-enabled medical devices registered with the US Food and Drug Administration (FDA) since 2020, AI is rapidly pervading healthcare systems. But like any other medical device, AI tools must be thoroughly assessed and follow strict regulations.

Joshua Hatherley, PhD, a postdoctoral fellow at the School of Philosophy and History of Ideas at Aarhus University in Denmark, said the traditional bioethical principles — autonomy, beneficence, nonmaleficence, and justice — remain a crucial framework for assessing ethics regarding the use of AI tools in medicine. However, he said the emerging fifth principle of “explainability” has gained attention due to the unique characteristics of AI systems.

“Everyone is excited about AI right now, but there are many open questions about how much we can trust it and to what extent we can use it,” Ana Catalina Hernandez Padilla, a clinical researcher at the Université de Limoges, France, told this news organization. 

Joseph Alderman, MBChB, an AI and digital health clinical research fellow at the Institute of Inflammation and Ageing at the University of Birmingham, UK, said these are undoubtedly exciting times to work in AI and health, but he believes clinicians should be “part of the story” and advocate for AI that is safe, effective, and equitable.
 

The Pros

Dr. Alderman said AI has huge potential to improve healthcare and patients’ experiences. 

One interesting area in which AI is being applied is the informed consent process. Conversational AI models, like large language models, can provide patients with a time-unlimited platform to discuss risks, benefits, and recommendations, potentially improving understanding and patient engagement. AI systems can also predict the preferences of noncommunicative patients by analyzing their social media and medical data, which may improve surrogate decision-making and ensure treatment aligns with patient preferences, Dr. Hatherley explained.

Another significant benefit is AI’s capacity to improve patient outcomes through better resource allocation. For example, AI can help optimize the allocation of hospital beds, leading to more efficient use of resources and improved patient health outcomes. 

AI systems can reduce medical errors and enhance diagnosis or treatment plans through large-scale data analysis, leading to faster and more accurate decision-making. It can handle administrative tasks, reducing clinician burnout and allowing healthcare professionals to focus more on patient care.

AI also promises to advance health equity by improving access to quality care in underserved areas. In rural hospitals or developing countries, AI can help fill gaps in clinical expertise, potentially leveling the playing field in access to healthcare.
 

The Cons

Despite its potential, AI in medicine presents several risks that require careful ethical considerations. One primary concern is the possibility of embedded bias in AI systems.

For example, AI-driven advice from an AI agent may prioritize certain outcomes, such as survival, based on broad standards rather than unique patient values, potentially misaligning with the preferences of patients who value quality of life over longevity. “That may interfere with patients’ autonomous decisions,” Dr. Hatherley said.

AI systems also have limited generalizability. Models trained on a specific patient population may perform poorly when applied to different groups due to changes in demographic or clinical characteristics. This can result in less accurate or inappropriate recommendations in real-world settings. “These technologies work on the very narrow population on which the tool was developed but might not necessarily work in the real world,” said Dr. Alderman.

Another significant risk is algorithmic bias, which can worsen health disparities. AI models trained on biased datasets may perpetuate or exacerbate existing inequities in healthcare delivery, leading to suboptimal care for marginalized populations. “We have evidence of algorithms directly discriminating against people with certain characteristics,” Dr. Alderman said.
 

AI’s Black Box

AI systems, particularly those utilizing deep learning, often function as “black boxes,” meaning their internal decision-making processes are opaque and difficult to interpret. Dr. Hatherley said this lack of transparency raises significant concerns about trust and accountability in clinical decision-making. 

While Explainable AI methods have been developed to offer insights into how these systems generate their recommendations, these explanations frequently fail to capture the reasoning process entirely. Dr. Hatherley explained that this is similar to using a pharmaceutical medicine without a clear understanding of the mechanisms for which it works.

This opacity in AI decision-making can lead to mistrust among clinicians and patients, limiting its effective use in healthcare. “We don’t really know how to interpret the information it provides,” Ms. Hernandez said. 

She said while younger clinicians might be more open to testing the waters with AI tools, older practitioners still prefer to trust their own senses while looking at a patient as a whole and observing the evolution of their disease. “They are not just ticking boxes. They interpret all these variables together to make a medical decision,” she said.

“I am really optimistic about the future of AI,” Dr. Hatherley concluded. “There are still many challenges to overcome, but, ultimately, it’s not enough to talk about how AI should be adapted to human beings. We also need to talk about how humans should adapt to AI.”

Dr. Hatherley, Dr. Alderman, and Ms. Hernandez have reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — Survival rates at 1 and 5 years for patients with pulmonary arterial hypertension (PAH) who receive bilateral lung and heart-lung transplants are similar, said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.

Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.

Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.

While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
 

No Survival Difference Between Bilateral Lung and Heart-Lung Transplants

Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.

The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.

Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.

A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
 

Cardiac Recovery Post-Bilateral Lung Transplant

Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.

Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.

The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.

“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”

Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — Survival rates at 1 and 5 years for patients with pulmonary arterial hypertension (PAH) who receive bilateral lung and heart-lung transplants are similar, said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.

Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.

Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.

While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
 

No Survival Difference Between Bilateral Lung and Heart-Lung Transplants

Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.

The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.

Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.

A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
 

Cardiac Recovery Post-Bilateral Lung Transplant

Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.

Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.

The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.

“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”

Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — Survival rates at 1 and 5 years for patients with pulmonary arterial hypertension (PAH) who receive bilateral lung and heart-lung transplants are similar, said researchers presenting at the European Respiratory Society (ERS) 2024 International Congress.

Transplant for end-stage PAH remains an important treatment option. Heart-lung transplantation plummeted from 91.7% to 21.4% between 1991 and 2014. Yet in the United States and Europe, PAH is the second most common reason to perform a heart-lung transplant, said Baharan Zarrabian, DO, a pulmonologist at the Mayo Clinic in Rochester, Minnesota.

Over the past decades, physicians have debated whether to opt for a bilateral lung or a heart-lung transplant. However, there is currently a lack of definitive cardiac indicators to guide the decision between the two procedures in patients with PAH.

While the lung condition has cardiac ramifications, some experts suggest that the heart can repair itself over time after a bilateral lung transplant.
 

No Survival Difference Between Bilateral Lung and Heart-Lung Transplants

Researchers compared the outcomes of bilateral lung transplantation with those of combined heart-lung transplantation in patients with PAH. They used data from the Organ Procurement and Transplantation Network, focusing on adult patients with PAH without congenital or structural cardiac abnormalities who underwent transplantation between June 2004 and September 2022.

The study included 918 patients, with the majority (84.6%) receiving bilateral lung transplants and 15.4% receiving heart-lung transplants. Pretransplant mean pulmonary arterial pressure and pulmonary vascular resistance were similar between the two groups. However, those who received bilateral lung transplants had higher cardiac output and lower pulmonary capillary wedge pressure than those who received heart-lung transplants. A higher percentage of heart-lung transplant recipients required extracorporeal membrane oxygenation (ECMO) before transplantation, while bilateral lung transplant recipients had longer median ischemic times.

Despite these differences in pretransplant characteristics and surgical factors, researchers found no significant difference in survival outcomes between the two groups at the 1-year and 5-year marks. Similarly, graft survival rates at 1 and 5 years posttransplant did not differ significantly between the two groups.

A higher proportion of patients who received bilateral lung transplant were on ECMO and remained intubated at 72 hours. “That did not translate into a worse outcome later on,” Dr. Zarrabian said.
 

Cardiac Recovery Post-Bilateral Lung Transplant

Saskia Bos, MD, PhD, a respiratory consultant, lung transplant physician, and transplant pulmonologist at University Hospitals Leuven, Belgium, who was not involved in the study, told this news organization that doctors have historically preferred combined heart-lung transplantation. The decision was motivated by a lack of understanding regarding whether the heart could remodel on its own. “Now we know that the right ventricle, which is the most affected part of the heart in pulmonary hypertension, has a huge ability to readapt to the new situation after just bilateral lung transplantation,” she said.

Bos suggested that in cases where a patient has pulmonary hypertension without any structural heart defects and where the left side of the heart is functioning normally, doctors can opt for a bilateral lung transplant rather than a combined heart-lung transplant. The right ventricle, typically the only part of the heart affected by the condition, can recover once the pulmonary hypertension is addressed through lung transplantation, she explained.

The advantage of bilateral lung transplantation over a heart-lung transplant is that the donor’s heart remains available for someone else.

“The recommendation is that physicians opt for a bilateral lung transplant,” Dr. Zarrabian concluded. “But we need to make that decision on a case-by-case basis because we still don’t know what are the cardiac parameters that we need to look for before the transplant to decide whether or not they should receive a bilateral lung or a heart-lung.”

Dr. Zarrabian and Dr. Bos reported no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.

Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities. Some clinicians believe that advances in mechanical and surgical techniques have made rtPA a thing of the past. Others think there is still insufficient evidence to support alternatives as the standard of care.

Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.

“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
 

The Case Against rtPA as the Standard of Care

High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.

Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.

ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.

Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained. 

Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%). 

When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.” 
 

rtPA Not a Matter of the Past

In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez. 

Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days. 

However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like  PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.

While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.

Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.

Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies. 

“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
 

The Debate Continues

Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.

“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.

Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.

Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities. Some clinicians believe that advances in mechanical and surgical techniques have made rtPA a thing of the past. Others think there is still insufficient evidence to support alternatives as the standard of care.

Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.

“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
 

The Case Against rtPA as the Standard of Care

High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.

Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.

ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.

Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained. 

Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%). 

When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.” 
 

rtPA Not a Matter of the Past

In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez. 

Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days. 

However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like  PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.

While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.

Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.

Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies. 

“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
 

The Debate Continues

Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.

“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.

Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

VIENNA — The optimal course of treatment when managing acute, high-risk pulmonary embolism (PE) remains a contentious topic among respiratory specialists.

Systemic thrombolysis, specifically using recombinant tissue plasminogen activator (rtPA), is the current gold standard treatment for high-risk PE. However, the real-world application is less straightforward due to patient complexities. Some clinicians believe that advances in mechanical and surgical techniques have made rtPA a thing of the past. Others think there is still insufficient evidence to support alternatives as the standard of care.

Here at the European Respiratory Society (ERS) 2024 Congress, respiratory specialists presented contrasting viewpoints and the latest evidence on each side of the issue to provide a comprehensive framework for navigating the complex decision-making process required for effective treatment.

“High-risk PE is a mechanical problem and thus needs a mechanical solution,” said Parth M. Rali, MD, an associate professor in thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia.

“The marketing on some of the mechanical techniques is very impressive,” said Olivier Sanchez, MD, a pulmonologist in the Department of Pneumology and Intensive Care at the Georges Pompidou European Hospital in France. “But what is the evidence of such treatment in the setting of pulmonary embolism?”
 

The Case Against rtPA as the Standard of Care

High-risk PE typically involves hemodynamically unstable patients presenting with conditions such as low blood pressure, cardiac arrest, or the need for mechanical circulatory support. There is a spectrum of severity within high-risk PE, making it a complex condition to manage, especially since many patients have comorbidities like anemia or active cancer, complicating treatment. “It’s a very dynamic and fluid condition, and we can’t take for granted that rtPA is a standard of care,” Dr. Rali said.

Alternative treatments such as catheter-directed therapies, extracorporeal membrane oxygenation (ECMO), and surgical embolectomy are emerging as promising options, especially for patients who do not respond to or cannot receive rtPA. Mechanical treatments offer benefits in reducing clot burden and stabilizing patients, but they come with their own challenges.

ECMO can stabilize patients who are in shock or cardiac arrest, buying time for the clot to resolve or for further interventions like surgery or catheter-based treatments, said Dr. Rali. However, it is an invasive procedure requiring cannulation of large blood vessels, often involving significant resources and expertise.

Catheter-directed thrombolysis is a minimally invasive technique where a catheter is inserted directly into the pulmonary artery to deliver thrombolytic drugs at lower doses. This method allows for more targeted treatment of the clot, reducing the risk for systemic bleeding that comes with higher doses of thrombolytic agents used in systemic therapy, Dr. Rali explained. 

Dr. Rali reported results from the FLAME study, which investigated the effectiveness of FlowTriever mechanical thrombectomy compared with conventional therapies for high-risk PE. This prospective, multicenter observational study enrolled 53 patients in the FlowTriever arm and 61 in the context arm, which included patients treated with systemic thrombolysis or anticoagulation. The primary endpoint, a composite of adverse in-hospital outcomes, was reached in 17% of FlowTriever patients, significantly lower than the 32% performance goal and the 63.9% rate in the context arm. In-hospital mortality was dramatically lower in the FlowTriever arm (1.9%) compared to the context arm (29.5%). 

When catheter-based treatment fails, surgical pulmonary embolectomy is a last-resort option. “Only a minority of the high-risk PE [patients] would qualify for rtPA without harmful side effects,” Dr. Rali concluded. “So think wise before you pull your trigger.” 
 

rtPA Not a Matter of the Past

In high-risk PE, the therapeutic priority is rapid hemodynamic stabilization and restoration of pulmonary blood flow to prevent cardiovascular collapse. Systemic thrombolysis acts quickly, reducing pulmonary vascular resistance and obstruction within hours, said Dr. Sanchez. 

Presenting at the ERS Congress, he reported numerous studies, including 15 randomized controlled trials that demonstrated its effectiveness in high-risk PE. The PEITHO trial, in particular, demonstrated the ability of systemic thrombolysis to reduce all-cause mortality and hemodynamic collapse within 7 days. 

However, this benefit comes at the cost of increased bleeding risk, including a 10% rate of major bleeding and a 2% risk for intracranial hemorrhage. “These data come from old studies using invasive diagnostic procedures, and with current diagnostic procedures, the rate of bleeding is probably lower,” Dr. Sanchez said. The risk of bleeding is also related to the type of thrombolytic agent, with tenecteplase being strongly associated with a higher risk of bleeding, while alteplase shows no increase in the risk of major bleeding, he added. New strategies like reduced-dose thrombolysis offer comparable efficacy and improved safety, as demonstrated in ongoing trials like  PEITHO-3, which aim to optimize the balance between efficacy and bleeding risk. Dr. Sanchez is the lead investigator of the PEITHO-3 study.

While rtPA might not be optimal for all patients, Dr. Sanchez thinks there is not enough evidence to replace it as a first-line treatment.

Existing studies on catheter-directed therapies often focus on surrogate endpoints, such as right-to-left ventricular ratio changes, rather than clinical outcomes like mortality, he said. Retrospective data suggest that catheter-directed therapies may reduce in-hospital mortality compared with systemic therapies, but they also increase the risk of intracranial bleeding, post-procedure complications, and device-related events.

Sanchez mentioned the same FLAME study described by Dr. Rali, which reported a 23% rate of device-related complications and 11% major bleeding in patients treated with catheter-directed therapies. 

“Systemic thrombolysis remains the first treatment of choice,” Dr. Sanchez concluded. “The use of catheter-directed treatment should be discussed as an alternative in case of contraindications.”
 

The Debate Continues

Numerous ongoing clinical studies, such as the FLARE trial, will address gaps in evidence and refine treatment protocols, potentially reshaping the standard of care in high-risk PE in the near future by providing new data on the efficacy and safety of existing and emerging therapies.

“The coming data will make it clearer what the best option is,” said Thamer Al Khouzaie, MD, a pulmonary medicine consultant at Johns Hopkins Aramco Healthcare in Dhahran, Saudi Arabia. For now, he said, systemic thrombolysis remains the best option for most patients because it is widely available, easily administered with intravenous infusion, and at a limited cost. Catheter-directed treatment and surgical options are only available in specialized centers, require expertise and training, and are also very expensive.

Dr. Rali, Dr. Sanchez, and Dr. Khouzaie report no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

The same dye that gives Twinkies their yellowish hue could be the key to invisibility. 

Applying the dye to lab mice made their skin temporarily transparent, allowing Stanford University researchers to observe the rodents’ digestive system, muscle fibers, and blood vessels, according to a study published in Science.

“It’s a stunning result,” said senior author Guosong Hong, PhD, who is assistant professor of materials science and engineering at Stanford University in California. “If the same technique could be applied to humans, it could offer a variety of benefits in biology, diagnostics, and even cosmetics.” 

The work drew upon optical concepts first described in the early 20th century to form a surprising theory: Applying a light-absorbing substance could render skin transparent by reducing the chaotic scattering of light as it strikes proteins, fats, and water in tissue. 

A search for a suitable light absorber led to FD&C Yellow 5, also called tartrazine, a synthetic color additive certified by the Food and Drug Administration (FDA) for use in foods, cosmetics, and medications. 

Rubbed on live mice (after areas of fur were removed using a drugstore depilatory cream), tartrazine rendered skin on their bellies, hind legs, and heads transparent within 5 minutes. With the naked eye, the researchers watched a mouse’s intestines, bladder, and liver at work. Using a microscope, they observed muscle fibers and saw blood vessels in a living mouse’s brain — all without making incisions. Transparency faded quickly when the dye was washed off.

Someday, the concept could be used in doctors’ offices and hospitals, Dr. Hong said. 

“Instead of relying on invasive biopsies, doctors might be able to diagnose deep-seated tumors by simply examining a person’s tissue without the need for invasive surgical removal,” he said. “This technique could potentially make blood draws less painful by helping phlebotomists easily locate veins under the skin. It could also enhance procedures like laser tattoo removal by allowing more precise targeting of the pigment beneath the skin.”
 

From Cake Frosting to Groundbreaking Research

Yellow 5 food dye can be found in everything from cereal, soda, spices, and cake frosting to lipstick, mouthwash, shampoo, dietary supplements, and house paint. Although it’s in some topical medications, more research is needed before it could be used in human diagnostics, said Christopher J. Rowlands, PhD, a senior lecturer in the Department of Bioengineering at Imperial College London, England, where he studies biophotonic instrumentation — ways to image structures inside the body more quickly and clearly. 

But the finding could prove useful in research. In a commentary published in Science, Dr. Rowlands and his colleague Jon Gorecki, PhD, an experimental optical physicist also at Imperial College London, noted that the dye could be an alternative to other optical clearing agents currently used in lab studies, such as glycerol, fructose, or acetic acid. Advantages are the effect is reversible and works at lower concentrations with fewer side effects. This could broaden the types of studies possible in lab animals, so researchers don’t have to rely on naturally transparent creatures like nematodes and zebrafish. 

The dye could also be paired with imaging techniques such as MRI or electron microscopy. 

“Imaging techniques all have pros and cons,” Dr. Rowlands said. “MRI can see all the way through the body albeit with limited resolution and contrast. Electron microscopy has excellent resolution but limited compatibility with live tissue and penetration depth. Optical microscopy has subcellular resolution, the ability to label things, excellent biocompatibility but less than 1 millimeter of penetration depth. This clearing method will give a substantial boost to optical imaging for medicine and biology.”

The discovery could improve the depth imaging equipment can achieve by tenfold, according to the commentary. 

Brain research especially stands to benefit. “Neurobiology in particular will have great use for combinations of multiphoton, optogenetics, and tissue clearing to record and control neural activity over (potentially) the whole mouse brain,” he said.
 

Refraction, Absorption, and The Invisible Man

The dye discovery has distant echoes in H.G. Wells’ 1897 novel The Invisible Man, Dr. Rowlands noted. In the book, a serum makes the main character invisible by changing the light scattering — or refractive index (RI) — of his cells to match the air around him.

The Stanford engineers looked to the past for inspiration, but not to fiction. They turned to a concept first described in the 1920s called the Kramers-Kronig relations, a mathematical principle that can be applied to relationships between the way light is refracted and absorbed in different materials. They also read up on Lorentz oscillation, which describes how electrons and atoms inside molecules react to light. 

They reasoned that light-absorbing compounds could equalize the differences between the light-scattering properties of proteins, lipids, and water that make skin opaque. 

With that, the search was on. The study’s first author, postdoctoral researcher Zihao Ou, PhD, began testing strong dyes to find a candidate. Tartrazine was a front-runner. 

“We found that dye molecules are more efficient in raising the refractive index of water than conventional RI-matching agents, thus resulting in transparency at a much lower concentration,” Dr. Hong said. “The underlying physics, explained by the Lorentz oscillator model and Kramers-Kronig relations, reveals that conventional RI matching agents like fructose are not as efficient because they are not ‘colored’ enough.”
 

What’s Next

Though the dye is already in products that people consume and apply to their skin, medical use is years away. In some people, tartrazine can cause skin or respiratory reactions. 

The National Science Foundation (NSF), which helped fund the research, posted a home or classroom activity related to the work on its website. It involves painting a tartrazine solution on a thin slice of raw chicken breast, making it transparent. The experiment should only be done while wearing a mask, eye protection, lab coat, and lab-quality nitrile gloves for protection, according to the NSF.

Meanwhile, Dr. Hong said his lab is looking for new compounds that will improve visibility through transparent skin, removing a red tone seen in the current experiments. And they’re looking for ways to induce cells to make their own “see-through” compounds. 

“We are exploring methods for cells to express intensely absorbing molecules endogenously, enabling genetically encoded tissue transparency in live animals,” he said.

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

With huge shifts over the past decade in the way doctors are employed — half of all doctors now work for a health system or large medical group — the idea of unionizing is not only being explored but gaining traction within the profession. In fact, 8% of the physician workforce (or 70,000 physicians) belong to a union, according to statistics gathered in 2022.

Exact numbers are hard to come by, and, interestingly, although the American Medical Association (AMA) “ supports the right of physicians to engage in collective bargaining,” the organization doesn’t track union membership among physicians, according to an AMA spokesperson. 
 

Forming a Union

One challenge is that forming a union is not only time-consuming but also difficult, owing to several barriers. For starters, the laws dictating unionization differ by state, and the rules governing unionization vary if a hospital is public or private. If there’s enough momentum from doctors leading unionization efforts, approval from hospital leaders is required before an official election can be requested from the National Labor Relations Board.

That said, for doctors who are in a union — the two most popular are the Union of American Physicians and Dentists and the Doctors Council branch of the Service Employees International Union (SEIU)—the benefits are immense, especially because union members can focus on what matters, such as providing the best patient care possible.

For a profession that historically has not been unionized, this year alone, nine medical residency programs at hospitals such as Stanford Health, Montefiore Medical Center, and the University of Pennsylvania, formed unions, reported WBUR in Boston.
 

Belonging Matters 

“When you build a relationship with your patients, it’s special, and that connection isn’t replaceable,” said Nicholas VenOsdel, MD, a pediatrician at Allina Health Primary Care in Hastings, Minnesota, and a union member of the Doctors Council. “However, a lot of us have felt like that hasn’t been respected as the climate of healthcare has changed so fast.”

In fact, autonomy over how much time doctors spend with patients is driving a lot of interest in unionization.

“We don’t necessarily have that autonomy now,” said Amber Higgins, MD, an emergency physician and an obstetrician at ChristianaCare, a hospital network in Newark, Delaware, and a member of the Doctors Council. “There are so many other demands, whether it’s billing, patient documentation, or other demands from the employer, and all of that takes time away from patient care.”

Another primary driver of physician unionization is the physician burnout epidemic. Physicians collectively complain that they spend more time on electronic health record documentation and bureaucratic administration. Yet if unions can improve these working conditions, the benefit to physicians and their patients would be a welcome change.

Union members are bullish and believe that having a cohesive voice will make a difference.

“We need to use our collective voices to get back to focusing on patient care instead of staring at a computer screen for 80% of the day,” Dr. Higgins told this news organization. “So much of medicine involves getting to the correct diagnosis, listening to patients, observing them, and building a relationship with them. We need time to build that.”

With corporate consolidation and a profit-driven mandate by healthcare systems, doctors are increasingly frustrated and feel that their voices haven’t been heard enough when it comes to issues like workplace safety, working hours, and benefits, said Stuart Bussey, MD, JD, a family practice physician and president of the Union of American Physicians and Dentists in Sacramento, California. 

However, he adds that urging doctors to join together to fight for a better working environment hasn’t been easy.

“Doctors are individualists, and they don’t know how to work in packs like hospital administrators do,” said Dr. Bussey. “They’re hard to organize, but I want them to understand that unless they join hands, sign petitions, and speak as one voice, they’re going to lose out on an amazing opportunity.”
 

Overcoming Misperceptions About Unions

One barrier to doctors getting involved is the sentiment that unions might do the opposite of what’s intended — that is, they might further reduce a doctor’s autonomy and work flexibility. Or there may be a perception that the drive to join a union is predicated on making more money. 

Though he’s now in a union, Dr. VenOsdel, who has been in a hospital-based practice for 7 years, admits that he initially felt very differently about unions than he does today.

“Even though I have family members in healthcare unions, I had a neutral to even slightly negative view of unions,” said Dr. VenOsdel. “It took me working directly with the Minnesota Nurses Association and the Doctors Council to learn the other side of the story.”

Armed with more information, he began lobbying for stricter rules about how his state’s large healthcare systems were closing hospitals and ending much-needed community services.

“I remember standing at the Capitol in Minnesota and telling one of the members that I once felt negatively about unions,” he added. “I realized then that I only knew what employers were telling me via such things as emails about strikes — that information was all being shared from the employers’ perspective.”

The other misperception is that unions only exist to argue against management, including against colleagues who are also part of the management structure, said Dr. Higgins.

“Some doctors perceive being in a union as ‘how can those same leaders also be in a union,’” she said. She feels that they currently don’t have leadership representing them that can help with such things as restructuring their support teams or getting them help with certain tasks. “That’s another way unions can help.” 
 

Social Justice Plays a Role

For Dr. VenOsdel, being part of a union has helped him return to what he calls the “art” of medicine.

“Philosophically, the union gave me an option for change in what felt like a hopeless situation,” he said. “It wasn’t just that I was tossing the keys to someone else and saying, ‘I can’t fix this.’ Instead, we’re taking the reins back and fixing things ourselves.”

Bussey argues that as the uneven balance between administrators and providers in many healthcare organizations grows, the time to consider forming a union is now.

“We’re in a $4 trillion medical industrial revolution,” he said. “Administrators and bureaucrats are multiplying 30-fold times vs providers, and most of that $4 trillion supports things that don’t contribute to the doctor-patient relationship.”

Furthermore, union proponents say that where a one-on-one relationship between doctor and patient once existed, that has now been “triangulated” to include administrators.

“We’ve lost power in every way,” Dr. Bussey said. “We have the degrees, the liability, and the knowledge — we should have more power to make our workplaces safer and better.”

Ultimately, for some unionized doctors, the very holding of a union card is rooted in supporting social justice issues.

“When doctors realize how powerful a tool a union can be for social justice and change, this will alter perceptions of unions within our profession,” Dr. VenOsdel said. “Our union helps give us a voice to stand up for other staff who aren’t unionized and, most importantly, to stand up for the patients who need us.”
 

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

With huge shifts over the past decade in the way doctors are employed — half of all doctors now work for a health system or large medical group — the idea of unionizing is not only being explored but gaining traction within the profession. In fact, 8% of the physician workforce (or 70,000 physicians) belong to a union, according to statistics gathered in 2022.

Exact numbers are hard to come by, and, interestingly, although the American Medical Association (AMA) “ supports the right of physicians to engage in collective bargaining,” the organization doesn’t track union membership among physicians, according to an AMA spokesperson. 
 

Forming a Union

One challenge is that forming a union is not only time-consuming but also difficult, owing to several barriers. For starters, the laws dictating unionization differ by state, and the rules governing unionization vary if a hospital is public or private. If there’s enough momentum from doctors leading unionization efforts, approval from hospital leaders is required before an official election can be requested from the National Labor Relations Board.

That said, for doctors who are in a union — the two most popular are the Union of American Physicians and Dentists and the Doctors Council branch of the Service Employees International Union (SEIU)—the benefits are immense, especially because union members can focus on what matters, such as providing the best patient care possible.

For a profession that historically has not been unionized, this year alone, nine medical residency programs at hospitals such as Stanford Health, Montefiore Medical Center, and the University of Pennsylvania, formed unions, reported WBUR in Boston.
 

Belonging Matters 

“When you build a relationship with your patients, it’s special, and that connection isn’t replaceable,” said Nicholas VenOsdel, MD, a pediatrician at Allina Health Primary Care in Hastings, Minnesota, and a union member of the Doctors Council. “However, a lot of us have felt like that hasn’t been respected as the climate of healthcare has changed so fast.”

In fact, autonomy over how much time doctors spend with patients is driving a lot of interest in unionization.

“We don’t necessarily have that autonomy now,” said Amber Higgins, MD, an emergency physician and an obstetrician at ChristianaCare, a hospital network in Newark, Delaware, and a member of the Doctors Council. “There are so many other demands, whether it’s billing, patient documentation, or other demands from the employer, and all of that takes time away from patient care.”

Another primary driver of physician unionization is the physician burnout epidemic. Physicians collectively complain that they spend more time on electronic health record documentation and bureaucratic administration. Yet if unions can improve these working conditions, the benefit to physicians and their patients would be a welcome change.

Union members are bullish and believe that having a cohesive voice will make a difference.

“We need to use our collective voices to get back to focusing on patient care instead of staring at a computer screen for 80% of the day,” Dr. Higgins told this news organization. “So much of medicine involves getting to the correct diagnosis, listening to patients, observing them, and building a relationship with them. We need time to build that.”

With corporate consolidation and a profit-driven mandate by healthcare systems, doctors are increasingly frustrated and feel that their voices haven’t been heard enough when it comes to issues like workplace safety, working hours, and benefits, said Stuart Bussey, MD, JD, a family practice physician and president of the Union of American Physicians and Dentists in Sacramento, California. 

However, he adds that urging doctors to join together to fight for a better working environment hasn’t been easy.

“Doctors are individualists, and they don’t know how to work in packs like hospital administrators do,” said Dr. Bussey. “They’re hard to organize, but I want them to understand that unless they join hands, sign petitions, and speak as one voice, they’re going to lose out on an amazing opportunity.”
 

Overcoming Misperceptions About Unions

One barrier to doctors getting involved is the sentiment that unions might do the opposite of what’s intended — that is, they might further reduce a doctor’s autonomy and work flexibility. Or there may be a perception that the drive to join a union is predicated on making more money. 

Though he’s now in a union, Dr. VenOsdel, who has been in a hospital-based practice for 7 years, admits that he initially felt very differently about unions than he does today.

“Even though I have family members in healthcare unions, I had a neutral to even slightly negative view of unions,” said Dr. VenOsdel. “It took me working directly with the Minnesota Nurses Association and the Doctors Council to learn the other side of the story.”

Armed with more information, he began lobbying for stricter rules about how his state’s large healthcare systems were closing hospitals and ending much-needed community services.

“I remember standing at the Capitol in Minnesota and telling one of the members that I once felt negatively about unions,” he added. “I realized then that I only knew what employers were telling me via such things as emails about strikes — that information was all being shared from the employers’ perspective.”

The other misperception is that unions only exist to argue against management, including against colleagues who are also part of the management structure, said Dr. Higgins.

“Some doctors perceive being in a union as ‘how can those same leaders also be in a union,’” she said. She feels that they currently don’t have leadership representing them that can help with such things as restructuring their support teams or getting them help with certain tasks. “That’s another way unions can help.” 
 

Social Justice Plays a Role

For Dr. VenOsdel, being part of a union has helped him return to what he calls the “art” of medicine.

“Philosophically, the union gave me an option for change in what felt like a hopeless situation,” he said. “It wasn’t just that I was tossing the keys to someone else and saying, ‘I can’t fix this.’ Instead, we’re taking the reins back and fixing things ourselves.”

Bussey argues that as the uneven balance between administrators and providers in many healthcare organizations grows, the time to consider forming a union is now.

“We’re in a $4 trillion medical industrial revolution,” he said. “Administrators and bureaucrats are multiplying 30-fold times vs providers, and most of that $4 trillion supports things that don’t contribute to the doctor-patient relationship.”

Furthermore, union proponents say that where a one-on-one relationship between doctor and patient once existed, that has now been “triangulated” to include administrators.

“We’ve lost power in every way,” Dr. Bussey said. “We have the degrees, the liability, and the knowledge — we should have more power to make our workplaces safer and better.”

Ultimately, for some unionized doctors, the very holding of a union card is rooted in supporting social justice issues.

“When doctors realize how powerful a tool a union can be for social justice and change, this will alter perceptions of unions within our profession,” Dr. VenOsdel said. “Our union helps give us a voice to stand up for other staff who aren’t unionized and, most importantly, to stand up for the patients who need us.”
 

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

With huge shifts over the past decade in the way doctors are employed — half of all doctors now work for a health system or large medical group — the idea of unionizing is not only being explored but gaining traction within the profession. In fact, 8% of the physician workforce (or 70,000 physicians) belong to a union, according to statistics gathered in 2022.

Exact numbers are hard to come by, and, interestingly, although the American Medical Association (AMA) “ supports the right of physicians to engage in collective bargaining,” the organization doesn’t track union membership among physicians, according to an AMA spokesperson. 
 

Forming a Union

One challenge is that forming a union is not only time-consuming but also difficult, owing to several barriers. For starters, the laws dictating unionization differ by state, and the rules governing unionization vary if a hospital is public or private. If there’s enough momentum from doctors leading unionization efforts, approval from hospital leaders is required before an official election can be requested from the National Labor Relations Board.

That said, for doctors who are in a union — the two most popular are the Union of American Physicians and Dentists and the Doctors Council branch of the Service Employees International Union (SEIU)—the benefits are immense, especially because union members can focus on what matters, such as providing the best patient care possible.

For a profession that historically has not been unionized, this year alone, nine medical residency programs at hospitals such as Stanford Health, Montefiore Medical Center, and the University of Pennsylvania, formed unions, reported WBUR in Boston.
 

Belonging Matters 

“When you build a relationship with your patients, it’s special, and that connection isn’t replaceable,” said Nicholas VenOsdel, MD, a pediatrician at Allina Health Primary Care in Hastings, Minnesota, and a union member of the Doctors Council. “However, a lot of us have felt like that hasn’t been respected as the climate of healthcare has changed so fast.”

In fact, autonomy over how much time doctors spend with patients is driving a lot of interest in unionization.

“We don’t necessarily have that autonomy now,” said Amber Higgins, MD, an emergency physician and an obstetrician at ChristianaCare, a hospital network in Newark, Delaware, and a member of the Doctors Council. “There are so many other demands, whether it’s billing, patient documentation, or other demands from the employer, and all of that takes time away from patient care.”

Another primary driver of physician unionization is the physician burnout epidemic. Physicians collectively complain that they spend more time on electronic health record documentation and bureaucratic administration. Yet if unions can improve these working conditions, the benefit to physicians and their patients would be a welcome change.

Union members are bullish and believe that having a cohesive voice will make a difference.

“We need to use our collective voices to get back to focusing on patient care instead of staring at a computer screen for 80% of the day,” Dr. Higgins told this news organization. “So much of medicine involves getting to the correct diagnosis, listening to patients, observing them, and building a relationship with them. We need time to build that.”

With corporate consolidation and a profit-driven mandate by healthcare systems, doctors are increasingly frustrated and feel that their voices haven’t been heard enough when it comes to issues like workplace safety, working hours, and benefits, said Stuart Bussey, MD, JD, a family practice physician and president of the Union of American Physicians and Dentists in Sacramento, California. 

However, he adds that urging doctors to join together to fight for a better working environment hasn’t been easy.

“Doctors are individualists, and they don’t know how to work in packs like hospital administrators do,” said Dr. Bussey. “They’re hard to organize, but I want them to understand that unless they join hands, sign petitions, and speak as one voice, they’re going to lose out on an amazing opportunity.”
 

Overcoming Misperceptions About Unions

One barrier to doctors getting involved is the sentiment that unions might do the opposite of what’s intended — that is, they might further reduce a doctor’s autonomy and work flexibility. Or there may be a perception that the drive to join a union is predicated on making more money. 

Though he’s now in a union, Dr. VenOsdel, who has been in a hospital-based practice for 7 years, admits that he initially felt very differently about unions than he does today.

“Even though I have family members in healthcare unions, I had a neutral to even slightly negative view of unions,” said Dr. VenOsdel. “It took me working directly with the Minnesota Nurses Association and the Doctors Council to learn the other side of the story.”

Armed with more information, he began lobbying for stricter rules about how his state’s large healthcare systems were closing hospitals and ending much-needed community services.

“I remember standing at the Capitol in Minnesota and telling one of the members that I once felt negatively about unions,” he added. “I realized then that I only knew what employers were telling me via such things as emails about strikes — that information was all being shared from the employers’ perspective.”

The other misperception is that unions only exist to argue against management, including against colleagues who are also part of the management structure, said Dr. Higgins.

“Some doctors perceive being in a union as ‘how can those same leaders also be in a union,’” she said. She feels that they currently don’t have leadership representing them that can help with such things as restructuring their support teams or getting them help with certain tasks. “That’s another way unions can help.” 
 

Social Justice Plays a Role

For Dr. VenOsdel, being part of a union has helped him return to what he calls the “art” of medicine.

“Philosophically, the union gave me an option for change in what felt like a hopeless situation,” he said. “It wasn’t just that I was tossing the keys to someone else and saying, ‘I can’t fix this.’ Instead, we’re taking the reins back and fixing things ourselves.”

Bussey argues that as the uneven balance between administrators and providers in many healthcare organizations grows, the time to consider forming a union is now.

“We’re in a $4 trillion medical industrial revolution,” he said. “Administrators and bureaucrats are multiplying 30-fold times vs providers, and most of that $4 trillion supports things that don’t contribute to the doctor-patient relationship.”

Furthermore, union proponents say that where a one-on-one relationship between doctor and patient once existed, that has now been “triangulated” to include administrators.

“We’ve lost power in every way,” Dr. Bussey said. “We have the degrees, the liability, and the knowledge — we should have more power to make our workplaces safer and better.”

Ultimately, for some unionized doctors, the very holding of a union card is rooted in supporting social justice issues.

“When doctors realize how powerful a tool a union can be for social justice and change, this will alter perceptions of unions within our profession,” Dr. VenOsdel said. “Our union helps give us a voice to stand up for other staff who aren’t unionized and, most importantly, to stand up for the patients who need us.”
 

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

First-line treatment with ivonescimab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared with pembrolizumab (Keytruda), in patients with programmed death ligand 1 (PD-L1)–positive advanced non–small cell lung cancer (NSCLC), according to recent findings from the HARMONi-2 trial. 

“This is the first randomized, phase 3 study to demonstrate a clinically significant improvement in efficacy with a novel drug compared to pembrolizumab in advanced NSCLC,” said study investigator Caicun Zhou, MD, PhD, with Shanghai Pulmonary Hospital in China, 

The results highlight ivonescimab’s potential to become a “new standard of care” in advanced PD-L1–positive advanced NSCLC, said Dr. Zhou, who presented the analysis at the annual International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in San Diego. Dr. Zhou is president-elect of the IASLC. 

Ivonescimab (AK112) is a novel, potentially first-in-class investigational bispecific antibody that targets PD-1 and vascular endothelial growth factor (VEGF) developed by Akeso Biopharma, which funded the HARMONi-2 trial. 

Conducted at 55 centers in China, HARMONi-2 enrolled 398 patients with untreated locally advanced or metastatic NSCLC, Eastern Cooperative Oncology Group Performance Status of 0 or 1, PD-L1 positive (with at least 1% of tumor cells expressing PD-L1), and no EGFR mutations or ALK rearrangements.

Patients were randomly allocated (1:1) to receive ivonescimab (20 mg/kg) or pembrolizumab (200 mg) every 3 weeks. The two groups were well balanced, and randomization was stratified by histology (squamous vs nonsquamous), clinical stage (IIIB/IIIC vs IV) and PD-L1 expression (PD-L1 of 1%-49% vs 50% or greater). 

Dr. Zhou reported that patients who received ivonescimab were progression free for nearly twice as long as those on pembrolizumab — a median of 11.1 vs 5.8 months, indicating a 49% lower risk for progression or death (stratified hazard ratio [HR], 0.51; P < .0001). 

The meaningful improvement in PFS with ivonescimab, compared with pembrolizumab, was “broadly consistent” in all prespecified subgroups, Dr. Zhou noted. That included patients with squamous NSCLC (HR, 0.48) and nonsquamous NSCLC (HR, 0.54), those with PD-L1 expression of 1%-49% (HR, 0.54) and 50% or higher (HR, 0.46), as well as those with liver metastases (HR, 0.47) and brain metastases (HR, 0.55). 

The PFS benefit seen with ivonescimab in HARMONi-2 is “striking,” and the results “highlight the potential benefits of combined VEGF and PD-1 blockade together,” said John Heymach, MD, with the University of Texas MD Anderson Cancer Center in Houston, who served as discussant for the study. 

Ivonescimab also led to a higher objective response rate (50% vs 38.5%) and disease control rate (89.9% vs 70.5%). 

Grade 3 or higher treatment-related adverse events occurred in more patients receiving ivonescimab — 29.4% vs 15.6% on pembrolizumab. The difference largely stemmed from higher rates of proteinuria, hypertension, and lab abnormalities.

The rates of serious treatment-related adverse events were similar between the groups —20.8% in the ivonescimab group and 16.1% in the pembrolizumab group. Rates of grade 3 or higher immune-related adverse events were also similar, occurring in 7% of patients treated with ivonescimab and 8% of those receiving pembrolizumab. 

In patients with squamous cell carcinoma, in particular, ivonescimab demonstrated a “very manageable” safety profile, Dr. Zhou noted. In this group, grade 3 or higher treatment-related adverse events occurred in 22.2% of patients (vs 18.7% receiving pembrolizumab).

Ivonescimab was associated with comparable but “numerically better” time to deterioration of global health status, based on the EORTC Core Quality of Life questionnaire, Dr. Zhou said. 

Although the “really impressive and clinically meaningful” PFS benefits extended across different subgroups, “we await the overall survival results and additional studies done outside of China to confirm the benefit seen,” Dr. Heymach noted.

He also cautioned that, for patients with low to intermediate PD-L1 expression (1%-49%), pembrolizumab monotherapy “would not be the relevant comparator in the US and the rest of the world, and different study designs are going to be required for those populations.”

Based on the results of HARMONi-2, Akeso’s partner, Summit Therapeutics, plans to initiate HARMONi-7 in early 2025. 

HARMONi-7 is currently planned as a multiregional, phase 3 clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (50% or more). 

Dr. Zhou has received consulting fees from Qilu Pharmaceutical, Hengrui, and TopAlliance Biosciences and honoraria from Eli Lilly China, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, Luye Pharma, TopAlliance Biosciences, Amoy Diagnostics, and AnHeart Therapeutics. Dr. Heymach is a consultant for AbbVie, AnHeart Therapeutics, ArriVent Biopharma, AstraZeneca, BioCurity Pharmaceuticals, BioNTech, Blueprint Medicines, Boehringer Ingelheim, BMS, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, Spectrum Pharmaceuticals, and Takeda.

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

First-line treatment with ivonescimab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared with pembrolizumab (Keytruda), in patients with programmed death ligand 1 (PD-L1)–positive advanced non–small cell lung cancer (NSCLC), according to recent findings from the HARMONi-2 trial. 

“This is the first randomized, phase 3 study to demonstrate a clinically significant improvement in efficacy with a novel drug compared to pembrolizumab in advanced NSCLC,” said study investigator Caicun Zhou, MD, PhD, with Shanghai Pulmonary Hospital in China, 

The results highlight ivonescimab’s potential to become a “new standard of care” in advanced PD-L1–positive advanced NSCLC, said Dr. Zhou, who presented the analysis at the annual International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in San Diego. Dr. Zhou is president-elect of the IASLC. 

Ivonescimab (AK112) is a novel, potentially first-in-class investigational bispecific antibody that targets PD-1 and vascular endothelial growth factor (VEGF) developed by Akeso Biopharma, which funded the HARMONi-2 trial. 

Conducted at 55 centers in China, HARMONi-2 enrolled 398 patients with untreated locally advanced or metastatic NSCLC, Eastern Cooperative Oncology Group Performance Status of 0 or 1, PD-L1 positive (with at least 1% of tumor cells expressing PD-L1), and no EGFR mutations or ALK rearrangements.

Patients were randomly allocated (1:1) to receive ivonescimab (20 mg/kg) or pembrolizumab (200 mg) every 3 weeks. The two groups were well balanced, and randomization was stratified by histology (squamous vs nonsquamous), clinical stage (IIIB/IIIC vs IV) and PD-L1 expression (PD-L1 of 1%-49% vs 50% or greater). 

Dr. Zhou reported that patients who received ivonescimab were progression free for nearly twice as long as those on pembrolizumab — a median of 11.1 vs 5.8 months, indicating a 49% lower risk for progression or death (stratified hazard ratio [HR], 0.51; P < .0001). 

The meaningful improvement in PFS with ivonescimab, compared with pembrolizumab, was “broadly consistent” in all prespecified subgroups, Dr. Zhou noted. That included patients with squamous NSCLC (HR, 0.48) and nonsquamous NSCLC (HR, 0.54), those with PD-L1 expression of 1%-49% (HR, 0.54) and 50% or higher (HR, 0.46), as well as those with liver metastases (HR, 0.47) and brain metastases (HR, 0.55). 

The PFS benefit seen with ivonescimab in HARMONi-2 is “striking,” and the results “highlight the potential benefits of combined VEGF and PD-1 blockade together,” said John Heymach, MD, with the University of Texas MD Anderson Cancer Center in Houston, who served as discussant for the study. 

Ivonescimab also led to a higher objective response rate (50% vs 38.5%) and disease control rate (89.9% vs 70.5%). 

Grade 3 or higher treatment-related adverse events occurred in more patients receiving ivonescimab — 29.4% vs 15.6% on pembrolizumab. The difference largely stemmed from higher rates of proteinuria, hypertension, and lab abnormalities.

The rates of serious treatment-related adverse events were similar between the groups —20.8% in the ivonescimab group and 16.1% in the pembrolizumab group. Rates of grade 3 or higher immune-related adverse events were also similar, occurring in 7% of patients treated with ivonescimab and 8% of those receiving pembrolizumab. 

In patients with squamous cell carcinoma, in particular, ivonescimab demonstrated a “very manageable” safety profile, Dr. Zhou noted. In this group, grade 3 or higher treatment-related adverse events occurred in 22.2% of patients (vs 18.7% receiving pembrolizumab).

Ivonescimab was associated with comparable but “numerically better” time to deterioration of global health status, based on the EORTC Core Quality of Life questionnaire, Dr. Zhou said. 

Although the “really impressive and clinically meaningful” PFS benefits extended across different subgroups, “we await the overall survival results and additional studies done outside of China to confirm the benefit seen,” Dr. Heymach noted.

He also cautioned that, for patients with low to intermediate PD-L1 expression (1%-49%), pembrolizumab monotherapy “would not be the relevant comparator in the US and the rest of the world, and different study designs are going to be required for those populations.”

Based on the results of HARMONi-2, Akeso’s partner, Summit Therapeutics, plans to initiate HARMONi-7 in early 2025. 

HARMONi-7 is currently planned as a multiregional, phase 3 clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (50% or more). 

Dr. Zhou has received consulting fees from Qilu Pharmaceutical, Hengrui, and TopAlliance Biosciences and honoraria from Eli Lilly China, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, Luye Pharma, TopAlliance Biosciences, Amoy Diagnostics, and AnHeart Therapeutics. Dr. Heymach is a consultant for AbbVie, AnHeart Therapeutics, ArriVent Biopharma, AstraZeneca, BioCurity Pharmaceuticals, BioNTech, Blueprint Medicines, Boehringer Ingelheim, BMS, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, Spectrum Pharmaceuticals, and Takeda.

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

First-line treatment with ivonescimab led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS), compared with pembrolizumab (Keytruda), in patients with programmed death ligand 1 (PD-L1)–positive advanced non–small cell lung cancer (NSCLC), according to recent findings from the HARMONi-2 trial. 

“This is the first randomized, phase 3 study to demonstrate a clinically significant improvement in efficacy with a novel drug compared to pembrolizumab in advanced NSCLC,” said study investigator Caicun Zhou, MD, PhD, with Shanghai Pulmonary Hospital in China, 

The results highlight ivonescimab’s potential to become a “new standard of care” in advanced PD-L1–positive advanced NSCLC, said Dr. Zhou, who presented the analysis at the annual International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in San Diego. Dr. Zhou is president-elect of the IASLC. 

Ivonescimab (AK112) is a novel, potentially first-in-class investigational bispecific antibody that targets PD-1 and vascular endothelial growth factor (VEGF) developed by Akeso Biopharma, which funded the HARMONi-2 trial. 

Conducted at 55 centers in China, HARMONi-2 enrolled 398 patients with untreated locally advanced or metastatic NSCLC, Eastern Cooperative Oncology Group Performance Status of 0 or 1, PD-L1 positive (with at least 1% of tumor cells expressing PD-L1), and no EGFR mutations or ALK rearrangements.

Patients were randomly allocated (1:1) to receive ivonescimab (20 mg/kg) or pembrolizumab (200 mg) every 3 weeks. The two groups were well balanced, and randomization was stratified by histology (squamous vs nonsquamous), clinical stage (IIIB/IIIC vs IV) and PD-L1 expression (PD-L1 of 1%-49% vs 50% or greater). 

Dr. Zhou reported that patients who received ivonescimab were progression free for nearly twice as long as those on pembrolizumab — a median of 11.1 vs 5.8 months, indicating a 49% lower risk for progression or death (stratified hazard ratio [HR], 0.51; P < .0001). 

The meaningful improvement in PFS with ivonescimab, compared with pembrolizumab, was “broadly consistent” in all prespecified subgroups, Dr. Zhou noted. That included patients with squamous NSCLC (HR, 0.48) and nonsquamous NSCLC (HR, 0.54), those with PD-L1 expression of 1%-49% (HR, 0.54) and 50% or higher (HR, 0.46), as well as those with liver metastases (HR, 0.47) and brain metastases (HR, 0.55). 

The PFS benefit seen with ivonescimab in HARMONi-2 is “striking,” and the results “highlight the potential benefits of combined VEGF and PD-1 blockade together,” said John Heymach, MD, with the University of Texas MD Anderson Cancer Center in Houston, who served as discussant for the study. 

Ivonescimab also led to a higher objective response rate (50% vs 38.5%) and disease control rate (89.9% vs 70.5%). 

Grade 3 or higher treatment-related adverse events occurred in more patients receiving ivonescimab — 29.4% vs 15.6% on pembrolizumab. The difference largely stemmed from higher rates of proteinuria, hypertension, and lab abnormalities.

The rates of serious treatment-related adverse events were similar between the groups —20.8% in the ivonescimab group and 16.1% in the pembrolizumab group. Rates of grade 3 or higher immune-related adverse events were also similar, occurring in 7% of patients treated with ivonescimab and 8% of those receiving pembrolizumab. 

In patients with squamous cell carcinoma, in particular, ivonescimab demonstrated a “very manageable” safety profile, Dr. Zhou noted. In this group, grade 3 or higher treatment-related adverse events occurred in 22.2% of patients (vs 18.7% receiving pembrolizumab).

Ivonescimab was associated with comparable but “numerically better” time to deterioration of global health status, based on the EORTC Core Quality of Life questionnaire, Dr. Zhou said. 

Although the “really impressive and clinically meaningful” PFS benefits extended across different subgroups, “we await the overall survival results and additional studies done outside of China to confirm the benefit seen,” Dr. Heymach noted.

He also cautioned that, for patients with low to intermediate PD-L1 expression (1%-49%), pembrolizumab monotherapy “would not be the relevant comparator in the US and the rest of the world, and different study designs are going to be required for those populations.”

Based on the results of HARMONi-2, Akeso’s partner, Summit Therapeutics, plans to initiate HARMONi-7 in early 2025. 

HARMONi-7 is currently planned as a multiregional, phase 3 clinical trial that will compare ivonescimab monotherapy to pembrolizumab monotherapy in patients with metastatic NSCLC whose tumors have high PD-L1 expression (50% or more). 

Dr. Zhou has received consulting fees from Qilu Pharmaceutical, Hengrui, and TopAlliance Biosciences and honoraria from Eli Lilly China, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, C-Stone, Luye Pharma, TopAlliance Biosciences, Amoy Diagnostics, and AnHeart Therapeutics. Dr. Heymach is a consultant for AbbVie, AnHeart Therapeutics, ArriVent Biopharma, AstraZeneca, BioCurity Pharmaceuticals, BioNTech, Blueprint Medicines, Boehringer Ingelheim, BMS, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen Pharmaceuticals, Mirati Therapeutics, Novartis Pharmaceuticals, Regeneron Pharmaceuticals, Sanofi, Spectrum Pharmaceuticals, and Takeda.

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

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

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

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

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

This transcript has been edited for clarity. 

New updated COVID vaccines are now available, but who can get them, who should get them, and when? Two updated mRNA COVID vaccines, one by Moderna and the other by Pfizer, have been authorized or approved by the US Food and Drug Administration (FDA) for those aged 6 months or older.

Both vaccines target Omicron’s KP.2 strain of the JN.1 lineage. An updated protein-based version by Novavax, also directed at JN.1, has been authorized, but only for those aged 12 years or older. 

The Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices recommends a dose of the 2024-2025 updated COVID vaccine for everyone aged 6 months or older. This includes people who have never been vaccinated against COVID, those who have been vaccinated, as well as people with previous COVID infection. 

The big question is when, and FDA and CDC have set some parameters. For mRNA updated vaccines, patients should wait at least 2 months after their last dose of any COVID vaccine before getting a dose of the updated vaccine.

If the patient has recently had COVID, the wait time is even longer: Patients can wait 3 months after a COVID infection to be vaccinated, but they don’t have to. FDA’s instructions for the Novavax version are not as straightforward. People can get an updated Novavax dose at least 2 months after their last mRNA COVID vaccine dose, or at least 2 months after completing a Novavax two-dose primary series. Those two Novavax doses should be given at least 3 weeks apart. 

Patients can personalize their vaccine plan. They will have the greatest protection in the first few weeks to months after a vaccine, after which antibodies tend to wane. It is a good idea to time vaccination so that protection peaks at big events like weddings and major meetings.

If patients decide to wait, they run the risk of getting a COVID infection. Also keep in mind which variants are circulating and the amount of local activity. Right now, there is a lot of COVID going around, and most of it is related to JN.1, the target of this year’s updated vaccine. If patients decide to wait, they should avoid crowded indoor settings or wear a high-quality mask for some protection. 

Here’s the bottom line: Most people (more than 95%) have some degree of COVID protection from previous infection, vaccination, or both. But if they haven’t recently had COVID infection and didn’t get a dose of last year’s vaccine, they are sitting ducks for getting sick without updated protection. The best way to stay well is to get a dose of the updated vaccine as soon as possible. This is especially true for those in high-risk groups or who are near someone who is high risk. 

Two thirds of COVID hospitalizations are in those aged 65 or older. Hospitalization rates are highest for those aged 75 or older and among infants under 6 months of age. These babies are too young to be vaccinated, but maternal vaccination during pregnancy and breastfeeding can help protect them. 

We’re still seeing racial and ethnic disparities in COVID-related hospitalizations, which are highest among American Indians, Alaska Natives, and Black populations. People with immunocompromising conditions, those with chronic medical conditions, and people living in long-term care facilities are also at greater risk. Unlike last year, additional mRNA doses are not recommended for those aged 65 or older at this time, but that could change.

Since 2020, we’ve come a long way in our fight against COVID, but the battle is still on. In 2023, nearly a million people were hospitalized from COVID. More than 75,000 died. COVID vaccines help protect us from severe disease, hospitalization, and death. 

Let’s face it — we all have booster fatigue, but COVID is now endemic. It’s here to stay, and it’s much safer to update antibody protection with vaccination than with infection. Another benefit of getting vaccinated is that it decreases the chance of getting long COVID. The uptake of last year’s COVID vaccine was abysmal; only about 23% of adults and 14% of children received it.

But this is a new year and a new vaccine. Please make sure your patients understand that the virus has changed a lot. Antibodies we built from previous infection and previous vaccination don’t work as well against these new variants. Antibody levels wane over time, so even if they missed the last few vaccine doses without getting sick, they really should consider getting a dose of this new vaccine. The 2024-2025 updated COVID vaccine is the best way to catch up, update their immunity, and keep them protected. 

Furthermore, we are now entering respiratory virus season, which means we need to think about, recommend, and administer three shots if indicated: COVID, flu, and RSV. Now is the time. Patients can get all three at the same time, in the same visit, if they choose to do so. 

Your recommendation as a physician is powerful. Adults and children who receive a healthcare provider recommendation are more likely to get vaccinated.

Dr. Fryhofer is an adjunct clinical associate professor of medicine, Emory University School of Medicine, Atlanta, Georgia. She reported conflicts of interest with the American Medical Association, the Medical Association of Atlanta, the American College of Physicians, and Medscape.

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