Mixed Topics

Release of our May issue coincides with our annual pilgrimage to Digestive Disease Week^® (DDW), this year held in our nation’s capital of Washington, D.C.

As we peruse the preliminary program in planning our meeting coverage, I am always amazed at the breadth and depth of programming offered as part of a relatively brief, 4-day meeting — this is a testament to the hard work of the AGA Council and DDW organizing committees, who have the gargantuan task of ensuring an engaging, seamless meeting each year.

University of Michigan

This year’s conference features over 400 original scientific sessions and 4,300 oral abstract and poster presentations, in addition to the always well-attended AGA Postgraduate Course. This year’s AGA Presidential Plenary, which will feature a series of thought-provoking panel discussions on the future of GI healthcare and innovations in how we treat, disseminate, and teach, also is not to be missed. Beyond DDW, I hope you will join me in taking advantage of some of D.C.’s amazing cultural offerings, including the Smithsonian museums, National Gallery, Kennedy Center for the Performing Arts, and many others.

In this month’s issue of GIHN, we highlight an important AGA expert consensus commentary published in Clinical Gastroenterology and Hepatology examining the role of blood-based tests (“liquid biopsy”) in colorectal cancer screening. This guidance, which recognizes the promise of such tests but also urges caution in their adoption, is particularly important considering recently published data from the ECLIPSE study (also covered in this issue) evaluating the performance of Guardant’s ctDNA liquid biopsy compared to a screening colonoscopy. Also relevant to CRC screening, we highlight data on the performance of the “next gen” Cologuard test compared with FIT, which was recently published in NEJM. In our May Member Spotlight, we feature gastroenterologist Adjoa Anyane-Yeboa, MD, MPH, who shares her passion for addressing barriers to CRC screening for Black patients. Finally, GIHN Associate Editor Dr. Avi Ketwaroo introduces our quarterly Perspectives column highlighting emerging applications of AI in GI endoscopy and hepatology. We hope you enjoy all the exciting content featured in this issue and look forward to seeing you in Washington, D.C. (or virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Release of our May issue coincides with our annual pilgrimage to Digestive Disease Week^® (DDW), this year held in our nation’s capital of Washington, D.C.

As we peruse the preliminary program in planning our meeting coverage, I am always amazed at the breadth and depth of programming offered as part of a relatively brief, 4-day meeting — this is a testament to the hard work of the AGA Council and DDW organizing committees, who have the gargantuan task of ensuring an engaging, seamless meeting each year.

University of Michigan

This year’s conference features over 400 original scientific sessions and 4,300 oral abstract and poster presentations, in addition to the always well-attended AGA Postgraduate Course. This year’s AGA Presidential Plenary, which will feature a series of thought-provoking panel discussions on the future of GI healthcare and innovations in how we treat, disseminate, and teach, also is not to be missed. Beyond DDW, I hope you will join me in taking advantage of some of D.C.’s amazing cultural offerings, including the Smithsonian museums, National Gallery, Kennedy Center for the Performing Arts, and many others.

In this month’s issue of GIHN, we highlight an important AGA expert consensus commentary published in Clinical Gastroenterology and Hepatology examining the role of blood-based tests (“liquid biopsy”) in colorectal cancer screening. This guidance, which recognizes the promise of such tests but also urges caution in their adoption, is particularly important considering recently published data from the ECLIPSE study (also covered in this issue) evaluating the performance of Guardant’s ctDNA liquid biopsy compared to a screening colonoscopy. Also relevant to CRC screening, we highlight data on the performance of the “next gen” Cologuard test compared with FIT, which was recently published in NEJM. In our May Member Spotlight, we feature gastroenterologist Adjoa Anyane-Yeboa, MD, MPH, who shares her passion for addressing barriers to CRC screening for Black patients. Finally, GIHN Associate Editor Dr. Avi Ketwaroo introduces our quarterly Perspectives column highlighting emerging applications of AI in GI endoscopy and hepatology. We hope you enjoy all the exciting content featured in this issue and look forward to seeing you in Washington, D.C. (or virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Release of our May issue coincides with our annual pilgrimage to Digestive Disease Week^® (DDW), this year held in our nation’s capital of Washington, D.C.

As we peruse the preliminary program in planning our meeting coverage, I am always amazed at the breadth and depth of programming offered as part of a relatively brief, 4-day meeting — this is a testament to the hard work of the AGA Council and DDW organizing committees, who have the gargantuan task of ensuring an engaging, seamless meeting each year.

University of Michigan

This year’s conference features over 400 original scientific sessions and 4,300 oral abstract and poster presentations, in addition to the always well-attended AGA Postgraduate Course. This year’s AGA Presidential Plenary, which will feature a series of thought-provoking panel discussions on the future of GI healthcare and innovations in how we treat, disseminate, and teach, also is not to be missed. Beyond DDW, I hope you will join me in taking advantage of some of D.C.’s amazing cultural offerings, including the Smithsonian museums, National Gallery, Kennedy Center for the Performing Arts, and many others.

In this month’s issue of GIHN, we highlight an important AGA expert consensus commentary published in Clinical Gastroenterology and Hepatology examining the role of blood-based tests (“liquid biopsy”) in colorectal cancer screening. This guidance, which recognizes the promise of such tests but also urges caution in their adoption, is particularly important considering recently published data from the ECLIPSE study (also covered in this issue) evaluating the performance of Guardant’s ctDNA liquid biopsy compared to a screening colonoscopy. Also relevant to CRC screening, we highlight data on the performance of the “next gen” Cologuard test compared with FIT, which was recently published in NEJM. In our May Member Spotlight, we feature gastroenterologist Adjoa Anyane-Yeboa, MD, MPH, who shares her passion for addressing barriers to CRC screening for Black patients. Finally, GIHN Associate Editor Dr. Avi Ketwaroo introduces our quarterly Perspectives column highlighting emerging applications of AI in GI endoscopy and hepatology. We hope you enjoy all the exciting content featured in this issue and look forward to seeing you in Washington, D.C. (or virtually) for DDW.
 

Megan A. Adams, MD, JD, MSc

Editor-in-Chief

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

The time interval between onset of interstitial lung disease (ILD) and diagnosis of anti–melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (DM) “has not been well described,” the authors say.

METHODOLOGY:

• MDA5 antibody-positive DM is a rare DM subtype associated with ILD, which is categorized into rapidly progressive ILD (RPILD) and chronic ILD, with the former having a particularly high mortality rate.
• In this retrospective cohort study using electronic medical records, researchers evaluated 774 patients with DM between 2008 and 2023 to learn more about the time interval between ILD and the time of an MDA5 antibody-positive DM diagnosis, which has not been well described.
• The primary outcome was ILD diagnosis and time in days between documented ILD and MDA5 antibody-positive DM diagnoses.

TAKEAWAY:

• Overall, 14 patients with DM (1.8%) were diagnosed with MDA5 antibody-positive DM in dermatology, rheumatology, or pulmonology departments (nine women and five men; age, 24-77 years; 79% were White and 7% were Black).
• ILD was diagnosed in 9 of the 14 patients (64%); 6 of the 14 (43%) met the criteria for RPILD. Two cases were diagnosed concurrently and two prior to MDA5 antibody-positive DM diagnosis.
• The median time between ILD and MDA5 antibody-positive DM diagnoses was 163 days.
• Gottron papules/sign and midfacial erythema were the most common dermatologic findings, and no association was seen between cutaneous signs and type of ILD.

IN PRACTICE:

“Establishing an accurate timeline between MDA5 antibody-positive DM and ILD can promote urgency among dermatologists to evaluate extracutaneous manifestations in their management of patients with DM for more accurate risk stratification and appropriate treatment,” the authors wrote.

SOURCE:

This study, led by Rachel R. Lin, from the University of Miami, Miami, Florida, was published online as a research letter in JAMA Dermatology.

LIMITATIONS:

Study limitations were the study’s retrospective design and small sample size.

DISCLOSURES:

No information on study funding was provided. One author reported personal fees from argenX outside this submitted work. Other authors did not disclose any competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Signals for keratoacanthoma and cutaneous squamous cell carcinoma (cSCC) with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors were detected in an analysis of adverse events (AEs) reported to the US Food and Drug Administration (FDA).

METHODOLOGY:

• The risk for dermatologic immune-related side effects may be increased with immunologic-modifying drugs.
• To determine if there are significant signals between keratoacanthomas and cSCCs and PD-1/PD-L1 inhibitors, researchers analyzed AEs associated with these agents reported to the FDA’s Adverse Event Reporting System (FAERS) between January 2004 and May 2023.
• Pharmacovigilance signals were identified, and a significant signal was defined as the lower 95% CI of a reporting odds ratio (ROR) greater than one or the lower 95% CI of an information component (IC) greater than 0.

TAKEAWAY:

• Of the 158,000 reports of PD-1/PD-L1 inhibitor use, 43 were in patients who developed a keratoacanthoma (mean age, 77 years; 39% women) and 83 were in patients who developed cSCC (mean age, 71 years; 41% women). Patients aged 60-79 years were most likely to develop keratoacanthomas and cSCC on these treatments.
• A PD-1/PD-L1 inhibitor was listed as the suspect drug in all 43 keratoacanthoma reports and in 70 of 83 cSCC reports (the remaining 13 listed them as the concomitant drug).
• Significant signals were reported for both keratoacanthoma (ROR, 9.7; IC, 1.9) and cSCC (ROR, 3.0; IC, 0.9) with PD-1/PD-L1 inhibitor use.
• Of the reports where this information was available, all 10 cases of PD-1/PD-L1 inhibitor–linked keratoacanthoma and 10 of 17 cases (59%) of PD-1/PD-L1 inhibitor–linked cSCC, resolution was noted following discontinuation or dose reduction of the inhibitor.

IN PRACTICE:

“Given the large number of patients receiving immunotherapy, FAERS recording only 43 patients developing keratoacanthoma and 83 patients developing cSCC highlights that these conditions are relatively rare adverse events,” the authors wrote but added that more studies are needed to confirm these results.

SOURCE:

The study, led by Pushkar Aggarwal, MD, MBA, of the Department of Dermatology, University of Cincinnati, Cincinnati, Ohio, was published online in JAMA Dermatology.

LIMITATIONS:

The data obtained from FAERS did not contain information on all AEs from drugs. In addition, a causal association could not be determined.

DISCLOSURES:

The funding source was not reported. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Signals for keratoacanthoma and cutaneous squamous cell carcinoma (cSCC) with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors were detected in an analysis of adverse events (AEs) reported to the US Food and Drug Administration (FDA).

METHODOLOGY:

• The risk for dermatologic immune-related side effects may be increased with immunologic-modifying drugs.
• To determine if there are significant signals between keratoacanthomas and cSCCs and PD-1/PD-L1 inhibitors, researchers analyzed AEs associated with these agents reported to the FDA’s Adverse Event Reporting System (FAERS) between January 2004 and May 2023.
• Pharmacovigilance signals were identified, and a significant signal was defined as the lower 95% CI of a reporting odds ratio (ROR) greater than one or the lower 95% CI of an information component (IC) greater than 0.

TAKEAWAY:

• Of the 158,000 reports of PD-1/PD-L1 inhibitor use, 43 were in patients who developed a keratoacanthoma (mean age, 77 years; 39% women) and 83 were in patients who developed cSCC (mean age, 71 years; 41% women). Patients aged 60-79 years were most likely to develop keratoacanthomas and cSCC on these treatments.
• A PD-1/PD-L1 inhibitor was listed as the suspect drug in all 43 keratoacanthoma reports and in 70 of 83 cSCC reports (the remaining 13 listed them as the concomitant drug).
• Significant signals were reported for both keratoacanthoma (ROR, 9.7; IC, 1.9) and cSCC (ROR, 3.0; IC, 0.9) with PD-1/PD-L1 inhibitor use.
• Of the reports where this information was available, all 10 cases of PD-1/PD-L1 inhibitor–linked keratoacanthoma and 10 of 17 cases (59%) of PD-1/PD-L1 inhibitor–linked cSCC, resolution was noted following discontinuation or dose reduction of the inhibitor.

IN PRACTICE:

“Given the large number of patients receiving immunotherapy, FAERS recording only 43 patients developing keratoacanthoma and 83 patients developing cSCC highlights that these conditions are relatively rare adverse events,” the authors wrote but added that more studies are needed to confirm these results.

SOURCE:

The study, led by Pushkar Aggarwal, MD, MBA, of the Department of Dermatology, University of Cincinnati, Cincinnati, Ohio, was published online in JAMA Dermatology.

LIMITATIONS:

The data obtained from FAERS did not contain information on all AEs from drugs. In addition, a causal association could not be determined.

DISCLOSURES:

The funding source was not reported. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Signals for keratoacanthoma and cutaneous squamous cell carcinoma (cSCC) with programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors were detected in an analysis of adverse events (AEs) reported to the US Food and Drug Administration (FDA).

METHODOLOGY:

• The risk for dermatologic immune-related side effects may be increased with immunologic-modifying drugs.
• To determine if there are significant signals between keratoacanthomas and cSCCs and PD-1/PD-L1 inhibitors, researchers analyzed AEs associated with these agents reported to the FDA’s Adverse Event Reporting System (FAERS) between January 2004 and May 2023.
• Pharmacovigilance signals were identified, and a significant signal was defined as the lower 95% CI of a reporting odds ratio (ROR) greater than one or the lower 95% CI of an information component (IC) greater than 0.

TAKEAWAY:

• Of the 158,000 reports of PD-1/PD-L1 inhibitor use, 43 were in patients who developed a keratoacanthoma (mean age, 77 years; 39% women) and 83 were in patients who developed cSCC (mean age, 71 years; 41% women). Patients aged 60-79 years were most likely to develop keratoacanthomas and cSCC on these treatments.
• A PD-1/PD-L1 inhibitor was listed as the suspect drug in all 43 keratoacanthoma reports and in 70 of 83 cSCC reports (the remaining 13 listed them as the concomitant drug).
• Significant signals were reported for both keratoacanthoma (ROR, 9.7; IC, 1.9) and cSCC (ROR, 3.0; IC, 0.9) with PD-1/PD-L1 inhibitor use.
• Of the reports where this information was available, all 10 cases of PD-1/PD-L1 inhibitor–linked keratoacanthoma and 10 of 17 cases (59%) of PD-1/PD-L1 inhibitor–linked cSCC, resolution was noted following discontinuation or dose reduction of the inhibitor.

IN PRACTICE:

“Given the large number of patients receiving immunotherapy, FAERS recording only 43 patients developing keratoacanthoma and 83 patients developing cSCC highlights that these conditions are relatively rare adverse events,” the authors wrote but added that more studies are needed to confirm these results.

SOURCE:

The study, led by Pushkar Aggarwal, MD, MBA, of the Department of Dermatology, University of Cincinnati, Cincinnati, Ohio, was published online in JAMA Dermatology.

LIMITATIONS:

The data obtained from FAERS did not contain information on all AEs from drugs. In addition, a causal association could not be determined.

DISCLOSURES:

The funding source was not reported. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

BY DEEPA VARMA

TOPLINE:

In patients with polycystic ovary syndrome (PCOS), laser and light therapies, alone or in combination with pharmacological agents, improve hirsutism and psychological well-being in women, according to the results of a systematic review.

METHODOLOGY:

• Hirsutism, which affects 70%-80% of women with PCOS, is frequently marginalized as a cosmetic issue by healthcare providers, despite its significant psychological repercussions, including diminished self-esteem, reduced quality of life, and heightened depression.
• The 2023 international evidence-based PCOS guideline considers managing hirsutism a priority in women with PCOS.
• Researchers reviewed six studies (four randomized controlled trials and two cohort studies), which included 423 patients with PCOS who underwent laser or light-based hair reduction therapies, published through 2022.
• The studies evaluated the alexandrite laser, diode laser, and intense pulsed light (IPL) therapy, with and without pharmacological treatments. The main outcomes were hirsutism severity, psychological outcome, and adverse events.

TAKEAWAY:

• Alexandrite laser (wavelength, 755 nm) showed effective hair reduction and improved patient satisfaction (one study); high-fluence treatment yielded better outcomes than low-fluence treatment (one study). Alexandrite laser 755 nm also showed longer hair-free intervals and greater hair reduction than IPL therapy at 650-1000 nm (one study).
• Combined IPL (600 nm) and metformin therapy improved hirsutism and hair count reduction compared with IPL alone, but with more side effects (one study).
• Diode laser treatments (810 nm) with combined oral contraceptives improved hirsutism and related quality of life measures compared with diode laser alone or with metformin (one study).
• Comparing two diode lasers (wavelengths, 810 nm), low-fluence, high repetition laser showed superior hair width reduction and lower pain scores than high fluence, low-repetition laser (one study).

IN PRACTICE:

Laser and light treatments alone or combined with other treatments have demonstrated “encouraging results in reducing hirsutism severity, enhancing psychological well-being, and improving overall quality of life for affected individuals,” the authors wrote, noting that additional high-quality trials evaluating these treatments, which include more patients with different skin tones, are needed.

SOURCE:

The first author of the review is Katrina Tan, MD, Monash Health, Department of Dermatology, Melbourne, Victoria, Australia, and it was published online in JAMA Dermatology.

LIMITATIONS:

Limitations include low certainty of evidence because of the observational nature of some of the studies, the small number of studies, and underrepresentation of darker skin types, limiting generalizability.

DISCLOSURES:

The review is part of an update to the PCOS guideline, which was funded by the Australian National Health and Medical Research Council through various organizations. Several authors reported receiving grants and personal fees outside this work. Dr. Tan was a member of the 2023 PCOS guideline evidence team. Other authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

The addition of an angiotensin-converting enzyme (ACE) inhibitor did not decrease risk for chemotherapy-related cardiac damage in patients being treated for breast cancer and non-Hodgkin lymphoma (NHL), a new randomized trial showed.

The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.

But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”

The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.

Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.

While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.

The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.

Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.

The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.

During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
 

Myocardial Injury Outcome

The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.

cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.

Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.

A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).

There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
 

Large Discrepancy

The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.

The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”

Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.

There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).

Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”

Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.

“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”

He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”

He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
 

Tough Population

Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.

“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”

Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”

And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”

The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.

Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.

“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”

Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”

The study was funded by the National Institute for Health and Care Research.

A version of this article appeared on Medscape.com.

The addition of an angiotensin-converting enzyme (ACE) inhibitor did not decrease risk for chemotherapy-related cardiac damage in patients being treated for breast cancer and non-Hodgkin lymphoma (NHL), a new randomized trial showed.

The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.

But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”

The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.

Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.

While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.

The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.

Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.

The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.

During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
 

Myocardial Injury Outcome

The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.

cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.

Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.

A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).

There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
 

Large Discrepancy

The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.

The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”

Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.

There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).

Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”

Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.

“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”

He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”

He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
 

Tough Population

Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.

“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”

Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”

And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”

The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.

Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.

“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”

Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”

The study was funded by the National Institute for Health and Care Research.

A version of this article appeared on Medscape.com.

The addition of an angiotensin-converting enzyme (ACE) inhibitor did not decrease risk for chemotherapy-related cardiac damage in patients being treated for breast cancer and non-Hodgkin lymphoma (NHL), a new randomized trial showed.

The results suggested adding an ACE inhibitor doesn’t affect cardiac injury or cardiac function outcomes “and should not be used as a preventative strategy” in these patients, David Austin, MD, consultant cardiologist, Academic Cardiovascular Unit, The James Cook University Hospital, Middlesbrough, England, and chief investigator for the PROACT study, told this news organization.

But while these negative results are disappointing, he said, “we now have a definitive result in a robustly conducted trial that will take the field forward.”

The findings were presented on April 8, 2024, at the American College of Cardiology (ACC) Scientific Session 2024.

Anthracyclines, which are extracted from Streptomyces bacterium, are chemotherapy drugs widely used to treat several types of cancer. Doxorubicin is among the most clinically important anthracyclines.

While extremely effective, anthracyclines can cause irreversible damage to cardiac cells and ultimately impair cardiac function and even cause heart failure, which may only be evident years after exposure. “Cardiac injury is very common in patients treated with high dose anthracyclines,” noted Dr. Austin.

The open-label PROACT study included 111 adult patients, mean age 58 years and predominantly White and women, being treated for breast cancer (62%) or NHL (38%) at National Health Service hospitals in England with high-dose anthracycline-based chemotherapy.

Patients were randomized to standard care (six cycles of high-dose doxorubicin-equivalent anthracycline-based chemotherapy) plus the ACE inhibitor enalapril maleate or standard care alone. The mean chemotherapy dose was 328 mg/m2; any dose greater than 300 is considered high.

The starting dose of enalapril was 2.5 mg twice a day, which was titrated up to a maximum of 10 mg twice a day. The ACE inhibitor was started at least 2 days before chemotherapy began and finished 3 weeks after the last anthracycline dose.

During the study, enalapril was titrated to 20 mg in more than 75% of patients, with the mean dose being 17.7 mg.
 

Myocardial Injury Outcome

The primary outcome was myocardial injury measured by the presence (≥ 14 ng/L) of high sensitivity cardiac troponin T (cTnT) during anthracycline treatment and 1 month after the last dose of anthracycline.

cTnT is highly expressed in cardiomyocytes and has become a preferred biomarker for detecting acute myocardial infarction and other causes of myocardial injury.

Blood sampling for cTnT and cardiac troponin I (cTnI) was performed at baseline, within 72 hours prior to chemotherapy and at trial completion. All patients had negative troponin results at baseline, indicating no heart damage.

A majority of patients experienced elevations in troponin (78% in the enalapril group and 83% in the standard of care group), but there was no statistically significant difference between groups (adjusted odds ratio [OR], 0.65; 95% CI, 0.23-1.78; P = .405).

There was also no significant difference between groups in terms of cTnI, a secondary endpoint. However, the proportion of patients testing positive for cTnI (47% in the enalapril group and 45% in controls) was substantially lower than that for cTnT.
 

Large Discrepancy

The “large discrepancy in the rate of injury” with cTnT “has implications for the clinical interpretation of cardiac biomarkers in routine practice, and we should proceed with caution,” Dr. Austin told this news organization.

The finding has implications because guidelines don’t currently differentiate based on the type of troponin, Dr. Austin said in a press release. “I was surprised by the difference, and I think this raises the question of what troponin we should be using.”

Secondary outcomes focused on cardiac function, measured using echocardiography and included left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF). These were measured at baseline, 4 weeks after the last anthracycline dose and 1 year after the final chemotherapy.

There was no between-group difference in LVGLS cardiac function (21% for enalapril vs 22% for standard of care; adjusted OR, 0.95; 95% CI, 0.33-2.74; P = .921). This was also true for LVEF (4% for enalapril vs 0% for standard of care group; adjusted OR, 4.89; 95% CI, 0.40-674.62; P = .236).

Asked what the research team plans to do next, Dr. Austin said “the immediate first step” is to continue following PROACT patients. “We know heart failure events and cardiac dysfunction can occur later down the line.”

Due to the challenge of enrolling patients into trials like PROACT, “we should come together as a sort of a broader cardiovascular/oncology academic community to try to understand how we can better recruit patients into these studies,” said Dr. Austin.

“We need to solve that problem before we then go on to maybe examine other potential preventative therapies.”

He doesn’t think an alternative ACE inhibitor would prove beneficial. “We need to look elsewhere for effective therapies in this area.”

He noted these new findings are “broadly consistent” with other trials that investigated angiotensin receptor blockers.
 

Tough Population

Commenting on the study during a media briefing, Anita Deswal, chair, medicine, Department of Cardiology, Division of Internal Medicine, The University of Texas, commended the researchers for managing to enroll patients with cancer as this is “a tough” population to get to agree to being in a clinical trial.

“These patients are often overwhelmed financially, physically, and emotionally with the cancer diagnosis, as well as the cancer therapy and, therefore, to enroll them in something to prevent, maybe, some potential cardiac toxicity down the line, is really hard.”

Past trials investigating neuro-hormonal blockers to prevent cardiotoxicity have been criticized for enrolling patients at “too low risk,” said Dr. Deswal. “But investigators here went that step beyond and enrolled patients who were going to receive higher doses of anthracyclines, so kudos to that.”

And she noted investigators managed to get patients on almost the maximum dose of enalapril. “So, the drug was poised to have an effect — if it was there.”

The negative results may have something to do with endpoints. “Maybe we haven’t quite figured out what are the cutoffs for high sensitivity troponin I that identify patients truly at risk” of developing heart failure in the future.

Commenting on the study for this news organization, Anu Lala, MD, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai, New York City, said the results may come as a surprise to some.

“ACE inhibitors are considered cardioprotective and for this reason are often used prophylactically in patients receiving chemotherapy.”

Dr. Lala agrees troponin may not be the right endpoint. “Another question is whether clinical outcomes should be followed in addition to symptoms or onset of any heart failure symptoms, which may hold greater prognostic significance.”

The study was funded by the National Institute for Health and Care Research.

A version of this article appeared on Medscape.com.

DENVER — A new test to detect pathogens related to meningitis, encephalitis, and other neurologic infections is more sensitive than are conventional diagnostics and could vastly improve diagnostic capabilities in the clinic, results of a real-world analysis show.

Metagenomic next-generation sequencing (mNGS) of RNA and DNA from cerebrospinal fluid (CSF) simultaneously tests for a wide range of infectious agents and identifies individual pathogens, including viruses, bacteria, fungi, and parasites. About half of patients with a suspected central nervous system (CNS) infection may go undiagnosed due to a lack of tools that detect rare pathogens. Although mNGS is currently available only in specialized laboratories, expanding access to the diagnostic could address this problem, investigators noted. 

“Our results justify incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients who present with potential central nervous system infections,” study investigator Charles Chiu, MD, PhD, professor in the Department of Laboratory Medicine as well as Medicine and Department of Medicine – Infectious Diseases and director of the Clinical Microbiology Laboratory, University of California San Fransisco (UCSF), said at a press conference.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

‘Real-World’ Performance

Accurate diagnosis of CNS infections on the basis of CSF, imaging, patient history, and presentation is challenging, the researchers noted. “Roughly 50% of patients who present with a presumed central nervous system infection actually end up without a diagnosis,” Dr. Chiu said.

This is due to the lack of diagnostic tests for rare pathogens and because noninfectious conditions like cancer, autoantibody syndrome, or vasculitis can mimic an infection, he added.

CSF is “very limiting,” Dr. Chiu noted. “We are unable, practically, from a volume perspective, as well as a cost and turnaround time perspective, to be able to send off every possible test for every possible organism.” 

The inability to rapidly pinpoint the cause of an infectious disease like meningitis or encephalitis can cause delays in appropriate treatment.

To assess the “real-world” performance of mNGS, researchers collected 4828 samples from mainly hospitalized patients across the United States and elsewhere from 2016 to 2023. 

Overall, the test detected at least one pathogen in 16.6% of cases. More than 70% were DNA or RNA viruses, followed by bacteria, fungi, and parasites. 
 

High Sensitivity

The technology was also able to detect novel or emerging neurotropic pathogens, including a yellow fever virus responsible for a transfusion-transmitted encephalitis outbreak and Fusarium solani, which caused a fungal meningitis outbreak.

Investigators also conducted a chart review on a subset of 1052 patients at UCSF to compare the performance of CSF nMGS testing with commonly used in-hospital diagnostic tests.

“We showed that as a single test, spinal fluid mNGS has an overall sensitivity of 63%, specificity of 99%, and accuracy of 90%,” said Dr. Chiu.

The sensitivity of mNGS was significantly higher compared with direct-detection testing from CSF (46%); direct-detection testing performed on samples other than CSF, such as blood (15%); and indirect serologic testing looking for antibodies (29%) (P < .001 for all). 

This suggests that mNGS could potentially “detect the hundreds of different pathogens that cause clinically indistinguishable infections,” Dr. Chui said.

mNGS testing is currently confined to large specialized or reference laboratories. For greater access to the test, routine clinical labs or hospital labs would have to implement it, said Dr. Chiu.

“If you can bring the technology to the point of care, directly to the hospital lab that’s running the test, we can produce results that would have a more rapid impact on patients,” he said.
 

Guiding Therapy

Ultimately, he added, the purpose of a diagnostic test is to “generate actionable information that could potentially guide therapy.”

Researchers are now evaluating medical charts of the same subcohort of patients to determine whether the test made a clinical difference.

“We want to know if it had a positive or negative or no clinical impact on the management and treatment of patients,” said Dr. Chiu. “Producing data like this will help us define the role of this test in the future as part of the diagnostic paradigm.”

The researchers are also working on a cost/benefit analysis, and Dr. Chiu said that US Food and Drug Administration approval of the test is needed “to establish a blueprint for reimbursement.”

Commenting on the findings, Jessica Robinson-Papp, MD, professor and vice chair of clinical research, Department of Neurology, Icahn School of Medicine, New York, said that the technology could be useful, especially in developing countries with higher rates of CNS infections. 

“What’s really exciting about it is you can take a very small CSF sample, like 1 mL, and in an unbiased way just screen for all different kinds of pathogens including both DNA and RNA viruses, parasites, bacteria, and fungi, and sort of come up with whether there’s a pathogen there or whether there is no pathogen there,” she said.

However, there’s a chance that this sensitive technique will pick up contaminants, she added. “For example, if there’s a little environmental bacterium either on the skin or in the water used for processing, it can get reads on that.”

The study received support from Delve Bio and the Chan-Zuckerberg Biohub.

Dr. Chiu has received personal compensation for serving on a Scientific Advisory or Data Safety Monitoring Board for Biomeme and has stock in Delve Bio, Poppy Health, Mammoth Biosciences, and BiomeSense and has received intellectual property interests from a discovery or technology relating to healthcare. Dr. Robinson-Papp has no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

DENVER — A new test to detect pathogens related to meningitis, encephalitis, and other neurologic infections is more sensitive than are conventional diagnostics and could vastly improve diagnostic capabilities in the clinic, results of a real-world analysis show.

Metagenomic next-generation sequencing (mNGS) of RNA and DNA from cerebrospinal fluid (CSF) simultaneously tests for a wide range of infectious agents and identifies individual pathogens, including viruses, bacteria, fungi, and parasites. About half of patients with a suspected central nervous system (CNS) infection may go undiagnosed due to a lack of tools that detect rare pathogens. Although mNGS is currently available only in specialized laboratories, expanding access to the diagnostic could address this problem, investigators noted. 

“Our results justify incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients who present with potential central nervous system infections,” study investigator Charles Chiu, MD, PhD, professor in the Department of Laboratory Medicine as well as Medicine and Department of Medicine – Infectious Diseases and director of the Clinical Microbiology Laboratory, University of California San Fransisco (UCSF), said at a press conference.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

‘Real-World’ Performance

Accurate diagnosis of CNS infections on the basis of CSF, imaging, patient history, and presentation is challenging, the researchers noted. “Roughly 50% of patients who present with a presumed central nervous system infection actually end up without a diagnosis,” Dr. Chiu said.

This is due to the lack of diagnostic tests for rare pathogens and because noninfectious conditions like cancer, autoantibody syndrome, or vasculitis can mimic an infection, he added.

CSF is “very limiting,” Dr. Chiu noted. “We are unable, practically, from a volume perspective, as well as a cost and turnaround time perspective, to be able to send off every possible test for every possible organism.” 

The inability to rapidly pinpoint the cause of an infectious disease like meningitis or encephalitis can cause delays in appropriate treatment.

To assess the “real-world” performance of mNGS, researchers collected 4828 samples from mainly hospitalized patients across the United States and elsewhere from 2016 to 2023. 

Overall, the test detected at least one pathogen in 16.6% of cases. More than 70% were DNA or RNA viruses, followed by bacteria, fungi, and parasites. 
 

High Sensitivity

The technology was also able to detect novel or emerging neurotropic pathogens, including a yellow fever virus responsible for a transfusion-transmitted encephalitis outbreak and Fusarium solani, which caused a fungal meningitis outbreak.

Investigators also conducted a chart review on a subset of 1052 patients at UCSF to compare the performance of CSF nMGS testing with commonly used in-hospital diagnostic tests.

“We showed that as a single test, spinal fluid mNGS has an overall sensitivity of 63%, specificity of 99%, and accuracy of 90%,” said Dr. Chiu.

The sensitivity of mNGS was significantly higher compared with direct-detection testing from CSF (46%); direct-detection testing performed on samples other than CSF, such as blood (15%); and indirect serologic testing looking for antibodies (29%) (P < .001 for all). 

This suggests that mNGS could potentially “detect the hundreds of different pathogens that cause clinically indistinguishable infections,” Dr. Chui said.

mNGS testing is currently confined to large specialized or reference laboratories. For greater access to the test, routine clinical labs or hospital labs would have to implement it, said Dr. Chiu.

“If you can bring the technology to the point of care, directly to the hospital lab that’s running the test, we can produce results that would have a more rapid impact on patients,” he said.
 

Guiding Therapy

Ultimately, he added, the purpose of a diagnostic test is to “generate actionable information that could potentially guide therapy.”

Researchers are now evaluating medical charts of the same subcohort of patients to determine whether the test made a clinical difference.

“We want to know if it had a positive or negative or no clinical impact on the management and treatment of patients,” said Dr. Chiu. “Producing data like this will help us define the role of this test in the future as part of the diagnostic paradigm.”

The researchers are also working on a cost/benefit analysis, and Dr. Chiu said that US Food and Drug Administration approval of the test is needed “to establish a blueprint for reimbursement.”

Commenting on the findings, Jessica Robinson-Papp, MD, professor and vice chair of clinical research, Department of Neurology, Icahn School of Medicine, New York, said that the technology could be useful, especially in developing countries with higher rates of CNS infections. 

“What’s really exciting about it is you can take a very small CSF sample, like 1 mL, and in an unbiased way just screen for all different kinds of pathogens including both DNA and RNA viruses, parasites, bacteria, and fungi, and sort of come up with whether there’s a pathogen there or whether there is no pathogen there,” she said.

However, there’s a chance that this sensitive technique will pick up contaminants, she added. “For example, if there’s a little environmental bacterium either on the skin or in the water used for processing, it can get reads on that.”

The study received support from Delve Bio and the Chan-Zuckerberg Biohub.

Dr. Chiu has received personal compensation for serving on a Scientific Advisory or Data Safety Monitoring Board for Biomeme and has stock in Delve Bio, Poppy Health, Mammoth Biosciences, and BiomeSense and has received intellectual property interests from a discovery or technology relating to healthcare. Dr. Robinson-Papp has no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

DENVER — A new test to detect pathogens related to meningitis, encephalitis, and other neurologic infections is more sensitive than are conventional diagnostics and could vastly improve diagnostic capabilities in the clinic, results of a real-world analysis show.

Metagenomic next-generation sequencing (mNGS) of RNA and DNA from cerebrospinal fluid (CSF) simultaneously tests for a wide range of infectious agents and identifies individual pathogens, including viruses, bacteria, fungi, and parasites. About half of patients with a suspected central nervous system (CNS) infection may go undiagnosed due to a lack of tools that detect rare pathogens. Although mNGS is currently available only in specialized laboratories, expanding access to the diagnostic could address this problem, investigators noted. 

“Our results justify incorporation of CSF mNGS testing as part of the routine diagnostic workup in hospitalized patients who present with potential central nervous system infections,” study investigator Charles Chiu, MD, PhD, professor in the Department of Laboratory Medicine as well as Medicine and Department of Medicine – Infectious Diseases and director of the Clinical Microbiology Laboratory, University of California San Fransisco (UCSF), said at a press conference.

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

‘Real-World’ Performance

Accurate diagnosis of CNS infections on the basis of CSF, imaging, patient history, and presentation is challenging, the researchers noted. “Roughly 50% of patients who present with a presumed central nervous system infection actually end up without a diagnosis,” Dr. Chiu said.

This is due to the lack of diagnostic tests for rare pathogens and because noninfectious conditions like cancer, autoantibody syndrome, or vasculitis can mimic an infection, he added.

CSF is “very limiting,” Dr. Chiu noted. “We are unable, practically, from a volume perspective, as well as a cost and turnaround time perspective, to be able to send off every possible test for every possible organism.” 

The inability to rapidly pinpoint the cause of an infectious disease like meningitis or encephalitis can cause delays in appropriate treatment.

To assess the “real-world” performance of mNGS, researchers collected 4828 samples from mainly hospitalized patients across the United States and elsewhere from 2016 to 2023. 

Overall, the test detected at least one pathogen in 16.6% of cases. More than 70% were DNA or RNA viruses, followed by bacteria, fungi, and parasites. 
 

High Sensitivity

The technology was also able to detect novel or emerging neurotropic pathogens, including a yellow fever virus responsible for a transfusion-transmitted encephalitis outbreak and Fusarium solani, which caused a fungal meningitis outbreak.

Investigators also conducted a chart review on a subset of 1052 patients at UCSF to compare the performance of CSF nMGS testing with commonly used in-hospital diagnostic tests.

“We showed that as a single test, spinal fluid mNGS has an overall sensitivity of 63%, specificity of 99%, and accuracy of 90%,” said Dr. Chiu.

The sensitivity of mNGS was significantly higher compared with direct-detection testing from CSF (46%); direct-detection testing performed on samples other than CSF, such as blood (15%); and indirect serologic testing looking for antibodies (29%) (P < .001 for all). 

This suggests that mNGS could potentially “detect the hundreds of different pathogens that cause clinically indistinguishable infections,” Dr. Chui said.

mNGS testing is currently confined to large specialized or reference laboratories. For greater access to the test, routine clinical labs or hospital labs would have to implement it, said Dr. Chiu.

“If you can bring the technology to the point of care, directly to the hospital lab that’s running the test, we can produce results that would have a more rapid impact on patients,” he said.
 

Guiding Therapy

Ultimately, he added, the purpose of a diagnostic test is to “generate actionable information that could potentially guide therapy.”

Researchers are now evaluating medical charts of the same subcohort of patients to determine whether the test made a clinical difference.

“We want to know if it had a positive or negative or no clinical impact on the management and treatment of patients,” said Dr. Chiu. “Producing data like this will help us define the role of this test in the future as part of the diagnostic paradigm.”

The researchers are also working on a cost/benefit analysis, and Dr. Chiu said that US Food and Drug Administration approval of the test is needed “to establish a blueprint for reimbursement.”

Commenting on the findings, Jessica Robinson-Papp, MD, professor and vice chair of clinical research, Department of Neurology, Icahn School of Medicine, New York, said that the technology could be useful, especially in developing countries with higher rates of CNS infections. 

“What’s really exciting about it is you can take a very small CSF sample, like 1 mL, and in an unbiased way just screen for all different kinds of pathogens including both DNA and RNA viruses, parasites, bacteria, and fungi, and sort of come up with whether there’s a pathogen there or whether there is no pathogen there,” she said.

However, there’s a chance that this sensitive technique will pick up contaminants, she added. “For example, if there’s a little environmental bacterium either on the skin or in the water used for processing, it can get reads on that.”

The study received support from Delve Bio and the Chan-Zuckerberg Biohub.

Dr. Chiu has received personal compensation for serving on a Scientific Advisory or Data Safety Monitoring Board for Biomeme and has stock in Delve Bio, Poppy Health, Mammoth Biosciences, and BiomeSense and has received intellectual property interests from a discovery or technology relating to healthcare. Dr. Robinson-Papp has no relevant conflicts of interest. 

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

An analysis of molecular-targeted cancer drug therapies recently approved in the United States found that fewer than one-third demonstrated substantial clinical benefits at the time of approval.

METHODOLOGY:

• The strength and quality of evidence supporting genome-targeted cancer drug approvals vary. A big reason is the growing number of cancer drug approvals based on surrogate endpoints, such as disease-free and progression-free survival, instead of clinical endpoints, such as overall survival or quality of life. The US Food and Drug Administration (FDA) has also approved genome-targeted cancer drugs based on phase 1 or single-arm trials.
• Given these less rigorous considerations for approval, “the validity and value of the targets and surrogate measures underlying FDA genome-targeted cancer drug approvals are uncertain,” the researchers explained.
• In the current analysis, researchers assessed the validity of the molecular targets as well as the clinical benefits of genome-targeted cancer drugs approved in the United States from 2015 to 2022 based on results from pivotal trials.
• The researchers evaluated the strength of evidence supporting molecular targetability using the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of Molecular Targets (ESCAT) and the clinical benefit using the ESMO–Magnitude of Clinical Benefit Scale (ESMO-MCBS).
• The authors defined a substantial clinical benefit as an A or B grade for curative intent and a 4 or 5 for noncurative intent. High-benefit genomic-based cancer treatments were defined as those associated with a substantial clinical benefit (ESMO-MCBS) and that qualified as ESCAT category level I-A (a clinical benefit based on prospective randomized data) or I-B (prospective nonrandomized data).

TAKEAWAY:

• The analyses focused on 50 molecular-targeted cancer drugs covering 84 indications. Of which, 45 indications (54%) were approved based on phase 1 or 2 pivotal trials, 45 (54%) were supported by single-arm pivotal trials and the remaining 39 (46%) by randomized trial, and 48 (57%) were approved based on subgroup analyses.
• Among the 84 indications, more than half (55%) of the pivotal trials supporting approval used overall response rate as a primary endpoint, 31% used progression-free survival, and 6% used disease-free survival. Only seven indications (8%) were supported by pivotal trials demonstrating an improvement in overall survival.
• Among the 84 trials, 24 (29%) met the ESMO-MCBS threshold for substantial clinical benefit.
• Overall, when combining all ratings, only 24 of the 84 indications (29%) were considered high-benefit genomic-based cancer treatments.

IN PRACTICE:

“We applied the ESMO-MCBS and ESCAT value frameworks to identify therapies and molecular targets providing high clinical value that should be widely available to patients” and “found that drug indications supported by these characteristics represent a minority of cancer drug approvals in recent years,” the authors said. Using these value frameworks could help payers, governments, and individual patients “prioritize the availability of high-value molecular-targeted therapies.”

SOURCE:

The study, with first author Ariadna Tibau, MD, PhD, Brigham and Women’s Hospital and Harvard Medical School, Boston, was published online in JAMA Oncology.

LIMITATIONS:

The study evaluated only trials that supported regulatory approval and did not include outcomes of postapproval clinical studies, which could lead to changes in ESMO-MCBS grades and ESCAT levels of evidence over time.

DISCLOSURES:

The study was funded by the Kaiser Permanente Institute for Health Policy, Arnold Ventures, and the Commonwealth Fund. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.