Federal Practitioner

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. This is Sex Matters, and I’m here today with my friend and colleague, Dr. Matt Ziegelmann, who is the sexual medicine expert at the Mayo Clinic and who does all things men’s health, including penile curvature, testosterone, and sexual function.

Let’s start with penile curvature. Many men come in very distressed. They felt a lump in their penis and go straight to their primary care physician. What do we do in that situation?

Matthew J. Ziegelmann, MD: Penile curvature (often due to Peyronie’s disease) is actually incredibly common; as many as 10% of men have this condition. We need to normalize it and let men know that this is something we see often, and we have treatments for it. One of the biggest concerns these men have is cancer, but I have yet to see this as an indicator of cancer.

Penile curvature has a significant impact on affected men — their relationships, psychological well-being, sexual functioning, and overall health. We can provide treatment if they are interested. A small subset of men are born with natural penile curvature, which is different from Peyronie’s disease. Natural curvature can still affect their mental health, and we have treatment options.

Rubin: What happens when a patient is referred to urology? We want to tell our patients what to expect. What’s in our toolbox to help patients with penile curvature?

Dr. Ziegelmann: Many patient resources are available. For example, the Sexual Medicine Society of North America (SMSNA) has a patient-facing website on sexual health with lots of information about Peyronie’s disease and other aspects of sexual health.

Patients who are bothered by their penile curvature can be referred to us to find out about treatment options, or even just to get reassurance. It might be as simple as a conversation and a physical exam — that’s all we need to make the diagnosis. We can provide reassurance and get an idea of how bothered they are by this condition without doing anything invasive.

If they are considering definitive treatment, we would need to do more invasive testing. Sometimes we have the patient bring in photos of their erection to help establish the change they see in the shape of their penis.

Dr. Rubin: What about the patient who asks, “Doc, did I do this to myself? Did I break my penis? What do I do?”

Dr. Ziegelmann: That’s a common question — “How the heck did this happen?” No, you didn’t do this to yourself. We still have much to understand about why this happens to some men. Our approach is to acknowledge what we do and don’t know, and partner with the patient to discuss treatment.

Dr. Rubin: It’s very important to support your patient’s mental health, because this can be really devastating. So, what are the treatment options from conservative to invasive? What do you recommend for patients?

Dr. Ziegelmann: It can be as simple as observation if the patient is just seeking reassurance that it’s not cancer. This is a benign condition, but for men who are more bothered by their curvature, we’ll talk about options. We have oral medications that help improved the rigidity of the penis. Many men are also suffering from inadequate functioning. We can use devices called traction or vacuum to stretch the area of the penis that’s curved. We can use injections of medications, including FDA-approved agents that are injected into the penis in the outpatient setting. For men who are either later in the treatment protocol or want to resolve the problem right away, we can offer surgical intervention. We have a host of options, and a very individualized approach and a shared decision-making model. It’s not a one-size-fits-all problem.

Dr. Rubin: The real takeaway is that there is a lot of hope for this condition. Many doctors care deeply about these issues and are ready to partner with specialists to figure out the right treatment strategy. The SMSNA is a great place to find a provider like Dr Ziegelmann or myself, or any of our incredible colleagues throughout North America and the world. Thank you for joining us today. 

Dr. Rubin is Assistant Clinical Professor, Department of Urology, Georgetown University, Washington, DC; Private practice, North Bethesda, Maryland. She disclosed ties with Sprout, Maternal Medical, Absorption Pharmaceuticals, GSK, and Endo.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) is warning against the use of smartwatches and rings that are claimed to measure a person’s glucose levels without piercing the skin.

The warning doesn’t apply to authorized smartwatch applications that display glucose values from an FDA-approved continuous glucose monitor with a sensor implanted under the skin.

Rather, the warning pertains to watches or rings sold through online marketplaces or directly from sellers who claim that the devices measure blood sugar noninvasively without requiring the wearer to prick their finger or pierce their skin. These products are manufactured by dozens of companies and sold under many different brand names. The FDA’s warning applies to all of them.

These devices have not been evaluated by the FDA for safety and effectiveness, and their use by people with diabetes could result in inaccurate blood glucose measurements, with potentially serious consequences if relied upon for medication dosing.

“The FDA has not authorized, cleared, or approved any smartwatch or smart ring that is intended to measure or estimate blood glucose values on its own,” the agency said in a statement issued on February 21, 2024.

They added, “The agency is working to ensure that manufacturers, distributors, and sellers do not illegally market unauthorized smartwatches or smart rings that claim to measure blood glucose levels.”

People who experience any problems with inaccurate blood glucose measurement or experience any adverse events from using an unauthorized smartwatch or smart ring are urged to report it to the FDA through its MedWatch program.

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Women may gain greater health benefits from regular physical activity at equivalent or lower doses of activity, compared with men, according to data from more than 400,000 US adults. 

Over two decades, with any regular physical activity, all-cause mortality risk was reduced by 24% in women vs 15% in men, and cardiovascular mortality risk was reduced by 36% and 14%, respectively, compared with inactivity, researchers found. 

Participating in strength training exercises (vs not) was associated with a reduced risk for all-cause death of 19% in women and 11% men and reductions in cardiovascular death of 30% and 11%, respectively.

“Women have historically and statistically lagged behind men in engaging in meaningful exercise,” co–lead author Martha Gulati, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement. “The beauty of this study is learning that women can get more out of each minute of moderate to vigorous activity than men do. It’s an incentivizing notion that we hope women will take to heart.”

The study was published online February 19 in the Journal of the American College of Cardiology. 
 

Sex-Specific Exercise Advice? 

The findings are based on leisure-time physical activity data collected over roughly 20 years via the National Health Interview Survey for 412,413 US adults aged 27-61 years. During roughly 4.9 million person-years of follow-up, there were 39,935 all-cause deaths and 11,670 cardiovascular deaths.

Both men and women achieved a peak survival benefit at 300 minutes of weekly moderate to vigorous aerobic physical activity. But the mortality reduction was substantially greater in women than in men for the same amount of regular exercise (24% vs 18%). 

Similarly, for any given dose of physical activity leading up to 300 minutes per week, women derived proportionately greater survival benefits than did men, the authors reported. 

“Importantly, the greater magnitude of physical activity-related survival benefit in women than men was consistently found across varied measures and types of physical activity including frequency, duration per session, and intensity of aerobic physical activity, as well as frequency of muscle strengthening activities,” they wrote. 

They say multiple factors, including variations in anatomy and physiology, may account for the differences in outcomes between men and women. For example, compared with men, women may use more respiratory, metabolic, and strength demands to conduct the same movement and in turn, reap greater health benefits.

The study also showed only 33% of women and 43% of men regularly engaged in aerobic physical activity, whereas only 20% of women and 28% of men completed a weekly strength training session.

“We hope this study will help everyone, especially women, understand they are poised to gain tremendous benefits from exercise,” senior author Susan Cheng, MD, with the Smidt Heart Institute at Cedars-Sinai, Los Angeles, said in a statement.

In an accompanying editorial, Wael A. Jaber, MD, and Erika Hutt, MD, from Cleveland Clinic Ohio, wrote that this analysis “brings us one step farther in gaining insights into the role and influence of physiological responses to exercise with a sex-specific lens.” 

The study is “well designed and adds important information to the body of literature that can potentially close the gender gap and optimize sex-specific physical activity recommendations by policy makers and societal guidelines,” they wrote. 

“This study emphasizes that there is no singular approach for exercise. A person’s physical activity needs and goals may change based on their age, health status, and schedule — but the value of any type of exercise is irrefutable,” Eric J. Shiroma, ScD, with the National Heart, Lung, and Blood Institute, said in a statement. 

The study was supported in part by grants from the National Institutes of Health. The authors and editorial writers have declared no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

Screening mammograms miss close to one in eight breast cancers. But early research suggests artificial intelligence (AI) could close this detection gap and markedly improve early diagnosis of the disease. Still, questions remain regarding how to best incorporate AI into screenings and whether it’s too soon to deploy the technology.

Already, some radiology clinics are offering AI analysis of mammograms through an add-on cost method.

Mammography patients who visit RadNet facilities, for example, have the option of an additional AI screening of their images. RadNet, the largest national owner and operator of fixed-site diagnostic imaging centers in the United States with more than 370 locations, first launched its AI program in the Northeast. The company has now rolled out its product across all regions in the country.

Because the AI is not reimbursed by insurers, patients must pay a $40 out-of-pocket fee if they want the AI analysis.

“RadNet practices have identified more than 400 women whose cancer was found earlier than it would have been had the AI not been present,” said Greg Sorensen MD, chief science officer for RadNet.
 

How RadNet’s AI Program Works

Patients coming to RadNet facilities for screening mammography undergo 3D high-resolution mammography that includes the use of 70-micron resolution detector technology, said Dr. Sorensen. The mammogram is reviewed by a qualified radiologist with assistance from two Food and Drug Administration–cleared AI programs, Saige-Q and Saige-Density. The radiologist then makes an interpretation.

Saige-Q is an AI tool that helps identify more suspicious mammograms by providing a quick signal to radiologists if the AI considers a given mammogram to be in a suspicious category, according to Dr. Sorensen. Saige-Density provides a density rating for each mammogram using one of the four standard categories:

• A. Almost entirely fatty
• B. Scattered areas of fibroglandular density
• C. Heterogeneously dense
• D. Extremely dense

Starting in September 2024, the FDA will require all mammogram reports to indicate density.

For patients who choose the $40 add-on service, called Enhanced Breast Cancer Detection, two other FDA-registered AI programs are also applied: Saige-Dx and Saige-Assure. These AI programs go a step further by placing marks on areas within the images that they find suspicious. Mammograms flagged as “high-suspicion” by the AI are then reviewed by a second human radiologist. The first and second radiologists confer to agree on a final diagnosis, Dr. Sorensen explained.

“Our research shows that approximately 20% more cancers are found when the safeguard review process is in place,” Dr. Sorensen said. “We also have seen [30%] decreases in recall rates” — the percentage of screening cases in which further tests are recommended by the radiologist.

Bethesda radiologist Janet Storella, MD, has used the AI program for about 3 years and said the technology has improved her screening performance.

The AI is linked to her practice’s imaging software, and radiologists have the option of turning the AI on at any time during their reading of screening mammograms, Dr. Storella explained. Some radiologists review the mammogram first and then initiate the AI, while others like Dr. Storella turn it on at the start, she said. Once initiated, the AI draws bounding boxes — or outlines — around areas that it deems suspicious.

The AI helps focus Dr. Storella’s attention on suspicious areas and grades the level of suspicion into one of four categories: high, intermediate, low, and minimal, she said.

“I find it especially useful in patients who have dense breast tissue,” said Dr. Storella, medical director of women’s imaging at Community Radiology Associates, a RadNet practice. “In these situations, the tissue on the mammogram is a field of white, and cancers are also white, so you’re looking for that little white golf ball on a sea of snow. The AI really helps hone that down to specific areas.”

About 35% of RadNet’s screening mammography patients have enrolled in the Enhanced Breast Cancer Detection program, according to RadNet data. In a recent study of nine general radiologists and nine breast imaging specialists, all radiologists improved their interpretation performance of DBT screening mammograms when reading with RadNet’s AI versus without it. (An average AUC [area under the receiver operating characteristic curve] of 0.93 versus 0.87, demonstrating a difference in AUC of 0.06 (95% CI, 0.04-0.08; P < .001)
 

Is Mammography Ready for AI?

RadNet is among a growing number of commercial companies offering AI solutions for mammography. MammoScreen and Hologic, for example, are two other companies that provide AI programs to assist radiologists in reading screening mammograms.

“We are at the start of the AI integration into breast imaging at this point,” said Laura Heacock, MD, a breast imaging radiologist and associate professor of radiology at NYU Langone Health. “There are multiple commercial AI models now available to radiologists to use in their practice [ and] there will likely be more. We’re in the transition stage where people are still deciding: Which is the best model to go with? How do I put it in my system? How do I ensure it works they way it was intended? Every practice and medical system will have a different answer to that question.”

At NYU Langone Health, researchers have been developing and studying optimal AI models for breast imaging for several years, Dr. Heacock said. Researchers thus far, have developed AI models for 2D digital mammography, 3D mammograms, breast ultrasound, and breast MRI. Similar to commercial AI systems, the AI is embedded into the picture archiving and communication (PACS) system used by radiologists to review images. Radiologists press a button to launch the AI, which draws a box around suspicious areas of the image and scores the suspicion.

“I take a look of where it is on the mammogram and decide whether that fits my level of suspicion,” Dr. Heacock said. The AI may not understand things about the mammogram like we do. For example, surgical scars look very suspicious to an AI model. But if I’m looking at a mammogram where [the patient] has had a stable scar that hasn’t changed in 10 years, I’m not concerned that the AI found it suspicious. My clinical judgment is the ultimate decider. This is just an additional piece of information that’s helpful to me.”

Research by New York University (NYU) has shown that when used by an expert radiologist the AI models have improved breast cancer detection in all four modalities, she said.

However, the AI has not yet launched at NYU Langone. More research is needed before deploying the technology, according to Dr. Heacock.

“At NYU, we are still testing the benefits to patients,” she said. “We know it improves cancer detection, but we want to make sure there are no drawbacks. We are still exploring the best ways to put it into effect at our institution.”

Dr. Heacock pointed to recent studies on AI in screening mammography that show promise.

An analysis of more than 80,000 women, for example, published in The Lancet Oncology in August, found that AI-supported screen reading led to a similar cancer detection rate as compared with a two-person reader system. This screening resulted in 244 screen-detected cancers, 861 recalls, and a total of 46,345 screen readings, according to the study. Standard screening resulted in 203 screen-detected cancers, 817 recalls, and a total of 83,231 screen readings.

The AI system also reduced the screen-reading workload for radiologists by 44%, the study found.

Meanwhile, a September 2023 study, published in The Lancet Digital Health, found that replacing one radiologist with AI resulted in more cancer detection without a large increase in false-positive cases. The AI led to a 4% higher, noninferior cancer detection rate, compared with radiologist double reading, the study found.

Dr. Heacock emphasized that both studies were conducted in Europe where the standard is for two radiologists to evaluate mammograms.

“That makes the results exciting, but not directly applicable to US practice just yet,” she said.
 

What Do the Experts Recommend?

Stamatia V. Destounis, MD, FACR, chair of the American College of Radiology (ACR) Breast Imaging Commission, said the college welcomes ongoing research into the efficacy of AI technologies and that AI may prove to be beneficial as an improved workflow tool.

The ACR has not released any guidance about the use of AI for radiologists and have no recommendation about best practices, Dr. Destounis said.

“The decisions regarding which technologies that various health systems and radiology sites choose to use are made by those facilities,” she said.

Dr. Destounis said more research is needed to demonstrate whether or not AI technologies help radiologists produce better results in identifying disease, injury, and illnesses among the general population or in specific groups — whether based on age, physical characteristics, race, ethnicity or risk status for breast cancer.

“Also, a way to measure each AI product is needed so that we can be certain they are relatively equivalent in their efficacy and accuracy — initially and over a prolonged period of time,” she said.

No consensus or concrete recommendation exists about the use of AI in mammography screening, adds Peter P. Yu, MD, FACP, FASCO, physician-in-chief at the Hartford HealthCare Cancer Institute and a member of the newly-created American Society of Clinical Oncology AI task force.

One of the many discussions concerning AI is to what degree patients should be aware that AI is being used in their healthcare and whether they should be required to give consent to its use, Dr. Yu said.

If AI is used to assist radiologists with mammographic interpretation, radiologists should discuss with patients how it’s being used and explain the ultimate reading is in the hands of their physician radiologist, he said.

“In the unlikely situation where there wasn’t a human in the loop and AI was in effect making a medical decision, the patient needs to be aware,” he said. “I’m not aware that any such situation exists today. AI is more likely to be subtly embedded in the software that operates technology, much like it is embedded in manufacturing and transportation.”
 

Who Will Pay for AI?

When it comes to payment, Dr. Yu said shifting the cost of AI to patients creates serious risk.

“It has enormous potential to increase health inequities,” he said. “If we believe health care is a fundamental human right, AI should inure to the benefit of all, not just those who can afford it. Healthcare should not be a luxury item; if it works, it works for all.”

In general, the issue of payment for AI is still pretty “thorny,” Dr. Heacock noted. Currently, there’s no way for physicians to request direct reimbursement for AI reads of mammograms.

While Dr. Heacock says she is sympathetic to the companies that spend significant time and effort on their AI technology, she doesn’t think charging patients is the right solution.

“We know that many women already have difficulty in paying for mammography-related services and this is just one more charge to confuse them or that they can’t pay,” she said.

Dr. Sorensen expects that, similar to 3D mammography, payers will eventually cover RadNet’s AI technology and that patients will no longer need to pay out of pocket. One Blue Cross carrier will start covering the AI in April 2024, he said.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

Exercising for upwards of 30 minutes most days may help relieve pain in patients who’ve been diagnosed with cancer, according to a study of exercise and pain outcomes from more than 60,000 people, including 10,000 with a history of cancer. 

Study participants who’d been diagnosed with cancer and surpassed 150 minutes of moderate activity a week were 16% less likely to report pain than those who did not exercise or who exercised less. Exercise was particularly helpful for those with moderate to severe pain. In general, the more people exercised, the less pain they felt — and that was true for those with and without a history of cancer.

“This adds to a large evidence base regarding other benefits of exercise after cancer,” said lead study author Christopher Swain, PhD, a researcher at the University of Melbourne, Australia, who studies how physical activity can protect against cancer. “It would be great for physicians to encourage physical activity” for anyone who’s ever been diagnosed with cancer. 

The findings also add to mounting evidence — including observational and experimental studies — that physical activity may help ease people’s pain. One large cross-sectional study of Norwegian adults found that the prevalence of chronic pain was 10%-38% lower among people who exercised. Randomized trials suggest exercise could be an effective pain management tool for a range of conditions, including neck and low-back pain, osteoarthritis, myofascial pain, and fibromyalgia. 

Still, the analgesic effects of exercise are less established for cancer-related pain, the authors wrote in the recent study published in Cancer — even though cancer pain remains a common and critical issue. 

Cancer-related pain is unique, stemming from multiple potential causes, said Shakil Ahmed, MB, an anesthesiologist at Weill Cornell Medicine who specializes in treating cancer pain. (Dr. Ahmed was not involved in the study.) Patients “might be having pain from the tumor itself,” — such as a tumor pressing on nerves — “or as a result of treatment, including surgery, radiation, chemotherapy, or complications from long-term medications,” Dr. Ahmed said. Indeed, some 40% of patients have chronic pain post cancer diagnosis, and it›s often undertreated and underdiagnosed.
 

How Does Exercise Reduce Pain?

Researchers aren’t exactly sure how exercise modulates pain, but they have some theories.

A 2021 meta-analysis found that exercise training can raise a person›s pain threshold, particularly at the pain site, suggesting adaptations in central inhibition, a process in the central nervous system that suppresses the perception of pain. This echoes a 2017 review that suggests exercise may help relieve pain by activating central inhibitory pathways. 

“There’s definitely evidence that there is improvement in the pain-reduction chemicals and augmentation of the pain inhibitory process in the central nervous system,” said Dr. Ahmed. That is, exercise may induce chemical changes that alter how much pain the brain’s sensory neurons can detect. 

Regular exercise can also reduce inflammation and improve blood flow, noted William McCarthy, PhD, a public health researcher with UCLA Health — both effects that may help to reduce pain.

Psychological factors may be another part of it. “There’s a lot of psychological stress as a result of a cancer diagnosis, which can lower the pain threshold,” said Dr. Ahmed. Exercise may help boost mood and reduce stress, increasing pain tolerance.

“People who are physically active also tend to be more socially active,” Dr. McCarthy added. “Engaging in social networks that provide social support can often palliate a sense of constant battling with fatigue, pain, and other negative effects of cancer.” Social activity, in turn, may promote physical activity: Studies show that when sedentary people socialize with active people, they become more active themselves — often by joining in walks or sports.

 

Help Patients Reap the Pain-Relieving Benefits of Exercise 

For beginners, the key to establishing a long-term exercise routine is to start low and slow, said Dr. Ahmed. That is, start with low-intensity activities like walking (walking was the most common activity reported in the study) or using light weights. Then, build slowly from there. 

Keep in mind that some pain or stiffness is normal at first, as one’s muscles and joints get used to the new activity. But be sure to investigate any new pain, Dr. Ahmed said. “Especially for patients who have had cancer, you want to see if the patient has any recurrence of disease,” Dr. Ahmed said. “That has to be kept in mind when you recommend any kind of exercise. “ 

It’s worth acknowledging that pain can be a significant barrier to exercise. If appropriate, you may consider referring out to exercise or physical therapy professionals in your network. Emphasizing the benefits of exercise — like the pain relief — may help motivate patients as well. 

For Dr. Swain, encouraging exercise is less about prescribing specific quantities and more about helping patients find activities “that give them enjoyment, that they feel comfortable doing, and that they can sustain over time.”

“The field needs to consider the different ways of supporting physical activity after a cancer diagnosis and treatment,” Dr. Swain said. “We have a lot of great research that shows the benefit of physical activity but not as strong an understanding of how to encourage and support it.”

A version of this article appeared on Medscape.com.

TOPLINE:

Gargling with mouthwash two to three times a day can reduce periodontopathic bacteria and possibly improve glycemic control in people with type 2 diabetes (T2D), especially younger adults.

METHODOLOGY:

• A total of 173 patients with T2D who had at least six total periodontopathic bacteria in their mouths and  ≥ 6.5% were instructed to gargle with water three times a day for 6 months, followed by gargling with chlorhexidine gluconate mouthwash three times a day for the next 6 months.
• Saliva specimens were collected every 1-2 months at clinic visits totaling 6-12 samples per study period and bacterial DNA examined for three red complex species, namely, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia.

TAKEAWAY:

• Twelve individuals who gargled once a day or less showed no significant reductions in red complex species after mouthwash or water gargling.
• By contrast, significant decreases in red complex bacteria were seen after 6 months of mouthwash gargling (P < .001) in the 80 who gargled twice a day and the 81 who did so three times a day compared with no changes after water gargling.
• Among the 161 individuals who gargled at least twice a day, the decrease in red species with mouthwash vs water gargling was highly significant (P < .0001).
• After adjustment for A1c seasonal variation, neither water gargling nor mouthwash gargling led to significant overall reduction in A1c levels.
• However, A1c levels were significantly lower in the 83 individuals aged ≤ 68 years than among the 78 aged ≥ 69 years after gargling with mouthwash (P < .05), with no change in either group after water gargling.
• Similarly, A1c levels were significantly reduced (P < .05) after mouthwash in the 69 with baseline A1c ≥ 7.5% compared with the 92 whose baseline A1c levels were ≤ 7.4%, with no changes in either after water.

IN PRACTICE:

“A bidirectional relationship between periodontitis and T2D has been reported. Patients with T2D are more susceptible to severe periodontitis than subjects without diabetes, and inflammatory periodontitis aggravates hyperglycemia, leading to inadequate glycemic control.” “Recently, it has been reported that patients with T2D treated for periodontitis have reduced periodontopathic bacteria and improved glycemic control. Patients with T2D complicated by periodontitis have more red complex species, and poor glycemic control is thought to be associated with increased levels of red complex species in the oral cavity.” “Further studies should be planned, taking into account various patient factors to determine the effect of mouthwash gargling on the amount of red complex species and A1c levels in patients with T2D.”

SOURCE:

This study was conducted by Saaya Matayoshi, of the Joint Research Laboratory of Science for Oral and Systemic Connection, Osaka University Graduate School of Dentistry, Osaka, Japan, and colleagues and published in Scientific Reports.

LIMITATIONS:

Only polymerase chain reaction used to detect periodontopathic bacteria so not quantified. No assessment of periodontal pocket depth. Saliva sampling conditions not standardized. Study conducted during COVID-19 pandemic; all patients wore masks. Heterogeneity in patient responses to the mouthwash.

DISCLOSURES:

This work was supported by the Fund for Scientific Promotion of Weltec Corp, Osaka, Japan. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Gargling with mouthwash two to three times a day can reduce periodontopathic bacteria and possibly improve glycemic control in people with type 2 diabetes (T2D), especially younger adults.

METHODOLOGY:

• A total of 173 patients with T2D who had at least six total periodontopathic bacteria in their mouths and  ≥ 6.5% were instructed to gargle with water three times a day for 6 months, followed by gargling with chlorhexidine gluconate mouthwash three times a day for the next 6 months.
• Saliva specimens were collected every 1-2 months at clinic visits totaling 6-12 samples per study period and bacterial DNA examined for three red complex species, namely, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia.

TAKEAWAY:

• Twelve individuals who gargled once a day or less showed no significant reductions in red complex species after mouthwash or water gargling.
• By contrast, significant decreases in red complex bacteria were seen after 6 months of mouthwash gargling (P < .001) in the 80 who gargled twice a day and the 81 who did so three times a day compared with no changes after water gargling.
• Among the 161 individuals who gargled at least twice a day, the decrease in red species with mouthwash vs water gargling was highly significant (P < .0001).
• After adjustment for A1c seasonal variation, neither water gargling nor mouthwash gargling led to significant overall reduction in A1c levels.
• However, A1c levels were significantly lower in the 83 individuals aged ≤ 68 years than among the 78 aged ≥ 69 years after gargling with mouthwash (P < .05), with no change in either group after water gargling.
• Similarly, A1c levels were significantly reduced (P < .05) after mouthwash in the 69 with baseline A1c ≥ 7.5% compared with the 92 whose baseline A1c levels were ≤ 7.4%, with no changes in either after water.

IN PRACTICE:

“A bidirectional relationship between periodontitis and T2D has been reported. Patients with T2D are more susceptible to severe periodontitis than subjects without diabetes, and inflammatory periodontitis aggravates hyperglycemia, leading to inadequate glycemic control.” “Recently, it has been reported that patients with T2D treated for periodontitis have reduced periodontopathic bacteria and improved glycemic control. Patients with T2D complicated by periodontitis have more red complex species, and poor glycemic control is thought to be associated with increased levels of red complex species in the oral cavity.” “Further studies should be planned, taking into account various patient factors to determine the effect of mouthwash gargling on the amount of red complex species and A1c levels in patients with T2D.”

SOURCE:

This study was conducted by Saaya Matayoshi, of the Joint Research Laboratory of Science for Oral and Systemic Connection, Osaka University Graduate School of Dentistry, Osaka, Japan, and colleagues and published in Scientific Reports.

LIMITATIONS:

Only polymerase chain reaction used to detect periodontopathic bacteria so not quantified. No assessment of periodontal pocket depth. Saliva sampling conditions not standardized. Study conducted during COVID-19 pandemic; all patients wore masks. Heterogeneity in patient responses to the mouthwash.

DISCLOSURES:

This work was supported by the Fund for Scientific Promotion of Weltec Corp, Osaka, Japan. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Gargling with mouthwash two to three times a day can reduce periodontopathic bacteria and possibly improve glycemic control in people with type 2 diabetes (T2D), especially younger adults.

METHODOLOGY:

• A total of 173 patients with T2D who had at least six total periodontopathic bacteria in their mouths and  ≥ 6.5% were instructed to gargle with water three times a day for 6 months, followed by gargling with chlorhexidine gluconate mouthwash three times a day for the next 6 months.
• Saliva specimens were collected every 1-2 months at clinic visits totaling 6-12 samples per study period and bacterial DNA examined for three red complex species, namely, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia.

TAKEAWAY:

• Twelve individuals who gargled once a day or less showed no significant reductions in red complex species after mouthwash or water gargling.
• By contrast, significant decreases in red complex bacteria were seen after 6 months of mouthwash gargling (P < .001) in the 80 who gargled twice a day and the 81 who did so three times a day compared with no changes after water gargling.
• Among the 161 individuals who gargled at least twice a day, the decrease in red species with mouthwash vs water gargling was highly significant (P < .0001).
• After adjustment for A1c seasonal variation, neither water gargling nor mouthwash gargling led to significant overall reduction in A1c levels.
• However, A1c levels were significantly lower in the 83 individuals aged ≤ 68 years than among the 78 aged ≥ 69 years after gargling with mouthwash (P < .05), with no change in either group after water gargling.
• Similarly, A1c levels were significantly reduced (P < .05) after mouthwash in the 69 with baseline A1c ≥ 7.5% compared with the 92 whose baseline A1c levels were ≤ 7.4%, with no changes in either after water.

IN PRACTICE:

“A bidirectional relationship between periodontitis and T2D has been reported. Patients with T2D are more susceptible to severe periodontitis than subjects without diabetes, and inflammatory periodontitis aggravates hyperglycemia, leading to inadequate glycemic control.” “Recently, it has been reported that patients with T2D treated for periodontitis have reduced periodontopathic bacteria and improved glycemic control. Patients with T2D complicated by periodontitis have more red complex species, and poor glycemic control is thought to be associated with increased levels of red complex species in the oral cavity.” “Further studies should be planned, taking into account various patient factors to determine the effect of mouthwash gargling on the amount of red complex species and A1c levels in patients with T2D.”

SOURCE:

This study was conducted by Saaya Matayoshi, of the Joint Research Laboratory of Science for Oral and Systemic Connection, Osaka University Graduate School of Dentistry, Osaka, Japan, and colleagues and published in Scientific Reports.

LIMITATIONS:

Only polymerase chain reaction used to detect periodontopathic bacteria so not quantified. No assessment of periodontal pocket depth. Saliva sampling conditions not standardized. Study conducted during COVID-19 pandemic; all patients wore masks. Heterogeneity in patient responses to the mouthwash.

DISCLOSURES:

This work was supported by the Fund for Scientific Promotion of Weltec Corp, Osaka, Japan. The authors declared no competing interests.

A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Poor communication between physician and patient can cause a lot of harm, according to Joseph N. Cappella, PhD, Gerald R. Miller Professor Emeritus of Communication at the University of Pennsylvania in Philadelphia, and Richard N. Street Jr, PhD, professor of communication and media science at Texas A&M University in Houston, Texas. When a physician and patient talk past each other, it may impair the patient’s compliance with preventive measures, screening, and treatment; undermine the physician-patient relationship; exacerbate fears and concerns; and possibly lead patients to rely on misleading, incomplete, or simply incorrect information, turning away from evidence-based medicine.

Drs. Cappella and Street made these points in an essay recently published in JAMA. The essay marks the beginning of the JAMA series Communicating Medicine.

“Helping clinicians deliver accurate information more effectively can lead to better-informed patients,” wrote Anne R. Cappola, MD, professor of endocrinology, diabetes, and metabolism at the University of Pennsylvania, and Kirsten Bibbins-Domingo, MD, PhD, professor of medicine at the University of California, San Francisco, in an accompanying editorial. Drs. Cappola and Bibbins-Domingo also are editors of JAMA.

To establish a common understanding between physician and patient, Drs. Cappella and Street identified the following four responsibilities of the physician:

• Discover what the patient understands and why
• Provide accurate information in an understandable manner
• Promote the credibility of the information
• Verify whether the patient has understood.

“Research has shown that although medical facts need to be the basis for the clinician’s core message, those facts are more effectively communicated in a patient-clinician relationship characterized by trust and cooperation and when the information is presented in a manner that fosters patient understanding,” wrote Drs. Cappella and Street. This approach includes using interpreters for patients who do not fluently speak the physician’s language and supplementing explanations with simple written information, images, and videos.

Patients generally believe their physician’s information, and most patients view their physicians as a trustworthy source. Trust is based on the belief that the physician has the patient’s best interests at heart.

However, patients may be distrustful of their physician’s information if it contradicts their own belief system or personal experiences or because they inherently distrust the medical profession.

In addition, patients are less willing to accept explanations and recommendations if they feel misunderstood, judged, discriminated against, or rushed by the physician. The basis for effective communication is a relationship with patients that is built on trust and respect. Empirically supported strategies for expressing respect and building trust include the following:

• Affirming the patient’s values
• Anticipating and addressing false or misleading information
• Using simple, jargon-free language
• Embedding facts into a story, rather than presenting the scientific evidence dryly.

“Conveying factual material using these techniques makes facts more engaging and memorable,” wrote Drs. Cappella and Street. It is crucial to inquire about and consider the patient’s perspective, health beliefs, assumptions, concerns, needs, and stories in the conversation.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.