Federal Practitioner

Scientists know that tinnitus, or ringing in the ears, affects 10% of adults worldwide. But they’re not exactly sure what causes the condition.

The traditional belief is that tinnitus happens in people who had already lost hearing. But some people who have tinnitus are still able to perform well on standard hearing tests, according to researchers at the Massachusetts Eye and Ear Infirmary. That happens because the tests don’t pick up auditory nerve loss, sometimes called “hidden hearing loss.” 

“Our work reconciles the idea that tinnitus may be triggered by a loss of auditory nerve, including in people with normal hearing,” Stéphane F. Maison, PhD, the lead author of a new study on tinnitus, said in a news release about the study.

Tinnitus is sometimes compared to phantom limb syndrome, in which people feel pain in limbs they no longer have. While the study published in Scientific Reports doesn’t refer to phantom limb syndrome, it does talk about “phantom sound.”

“In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, tinnitus. Until recently though, this idea was disputed as some tinnitus sufferers have normal hearing tests,” the researchers explained in the news release. 

Annoyed by the ringing in your ears? What causes tinnitus, and how can you get the sound to buzz off?

The study included 294 adults — 201 who had never reported having tinnitus, 64 who had reported having temporary tinnitus, and 29 who had reported having constant tinnitus for 6 months or more. 

All 294 had performed normally on a pure tone test, in which subjects raise their hands when they hear beeps to measure the quietest sounds they can detect.

In a different kind of test, electrodes measured responses to clicking sounds in the inner ear, the auditory nerve, and the brain. The second test found reduced response in the auditory nerves and increased activity in the brainstem activity among those who had tinnitus.

Dr Maison, a principal investigator at Eaton-Peabody Laboratories at Mass Eye and Ear/Harvard Medical School, called the study “a first step toward our ultimate goal of silencing tinnitus.”

“Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety and depression, adversely affecting work performance, and reducing significantly their quality of life,” he said in the news release. “We won’t be able to cure tinnitus until we fully understand the mechanisms underlying its genesis.”

A version of this article appeared on WebMD.com.

Scientists know that tinnitus, or ringing in the ears, affects 10% of adults worldwide. But they’re not exactly sure what causes the condition.

The traditional belief is that tinnitus happens in people who had already lost hearing. But some people who have tinnitus are still able to perform well on standard hearing tests, according to researchers at the Massachusetts Eye and Ear Infirmary. That happens because the tests don’t pick up auditory nerve loss, sometimes called “hidden hearing loss.” 

“Our work reconciles the idea that tinnitus may be triggered by a loss of auditory nerve, including in people with normal hearing,” Stéphane F. Maison, PhD, the lead author of a new study on tinnitus, said in a news release about the study.

Tinnitus is sometimes compared to phantom limb syndrome, in which people feel pain in limbs they no longer have. While the study published in Scientific Reports doesn’t refer to phantom limb syndrome, it does talk about “phantom sound.”

“In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, tinnitus. Until recently though, this idea was disputed as some tinnitus sufferers have normal hearing tests,” the researchers explained in the news release. 

Annoyed by the ringing in your ears? What causes tinnitus, and how can you get the sound to buzz off?

The study included 294 adults — 201 who had never reported having tinnitus, 64 who had reported having temporary tinnitus, and 29 who had reported having constant tinnitus for 6 months or more. 

All 294 had performed normally on a pure tone test, in which subjects raise their hands when they hear beeps to measure the quietest sounds they can detect.

In a different kind of test, electrodes measured responses to clicking sounds in the inner ear, the auditory nerve, and the brain. The second test found reduced response in the auditory nerves and increased activity in the brainstem activity among those who had tinnitus.

Dr Maison, a principal investigator at Eaton-Peabody Laboratories at Mass Eye and Ear/Harvard Medical School, called the study “a first step toward our ultimate goal of silencing tinnitus.”

“Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety and depression, adversely affecting work performance, and reducing significantly their quality of life,” he said in the news release. “We won’t be able to cure tinnitus until we fully understand the mechanisms underlying its genesis.”

A version of this article appeared on WebMD.com.

Scientists know that tinnitus, or ringing in the ears, affects 10% of adults worldwide. But they’re not exactly sure what causes the condition.

The traditional belief is that tinnitus happens in people who had already lost hearing. But some people who have tinnitus are still able to perform well on standard hearing tests, according to researchers at the Massachusetts Eye and Ear Infirmary. That happens because the tests don’t pick up auditory nerve loss, sometimes called “hidden hearing loss.” 

“Our work reconciles the idea that tinnitus may be triggered by a loss of auditory nerve, including in people with normal hearing,” Stéphane F. Maison, PhD, the lead author of a new study on tinnitus, said in a news release about the study.

Tinnitus is sometimes compared to phantom limb syndrome, in which people feel pain in limbs they no longer have. While the study published in Scientific Reports doesn’t refer to phantom limb syndrome, it does talk about “phantom sound.”

“In other words, the brain tries to compensate for the loss of hearing by increasing its activity, resulting in the perception of a phantom sound, tinnitus. Until recently though, this idea was disputed as some tinnitus sufferers have normal hearing tests,” the researchers explained in the news release. 

Annoyed by the ringing in your ears? What causes tinnitus, and how can you get the sound to buzz off?

The study included 294 adults — 201 who had never reported having tinnitus, 64 who had reported having temporary tinnitus, and 29 who had reported having constant tinnitus for 6 months or more. 

All 294 had performed normally on a pure tone test, in which subjects raise their hands when they hear beeps to measure the quietest sounds they can detect.

In a different kind of test, electrodes measured responses to clicking sounds in the inner ear, the auditory nerve, and the brain. The second test found reduced response in the auditory nerves and increased activity in the brainstem activity among those who had tinnitus.

Dr Maison, a principal investigator at Eaton-Peabody Laboratories at Mass Eye and Ear/Harvard Medical School, called the study “a first step toward our ultimate goal of silencing tinnitus.”

“Beyond the nuisance of having persistent ringing or other sounds in the ears, tinnitus symptoms are debilitating in many patients, causing sleep deprivation, social isolation, anxiety and depression, adversely affecting work performance, and reducing significantly their quality of life,” he said in the news release. “We won’t be able to cure tinnitus until we fully understand the mechanisms underlying its genesis.”

A version of this article appeared on WebMD.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

Some call the drug “ecstasy” or “molly.” Researchers are calling it a potential tool to help treat loneliness.

As public health experts sound the alarm on a rising loneliness epidemic in the United States and across the globe, early research is finding that MDMA could increase social connectedness and reduce defensiveness in some people — effects that some say could, in combination with therapy, help combat loneliness. 

In the latest study, MDMA “led to a robust increase in feelings of connection” among people socializing in a controlled setting. Participants were dosed with either MDMA or a placebo and asked to chat with a stranger. Afterward, those who took MDMA said their companion was more responsive and attentive, and that they had plenty in common. The drug also “increased participants’ ratings of liking their partners, feeling connected and finding the conversation enjoyable and meaningful.” 

The study was small — just 18 participants — but its results “have implications for MDMA-assisted therapy,” the authors wrote. “This feeling of connectedness could help patients feel safe and trusting, thereby facilitating deeper emotional exploration.” 

MDMA “really does seem to make people want to interact more with other people,” says Harriet de Wit, PhD, a neuropharmacologist at the University of Chicago and one of the study’s authors. The results echo those of earlier research using psychedelics like LSD or psilocybin. 

It’s important to note that any intervention involving MDMA or psychedelics would be a drug-assisted therapy — that is, used in conjunction with the appropriate therapy and in a therapeutic setting. MDMA-assisted therapy has already drawn popular and scientific attention, as it recently cleared clinical trials for treating posttraumatic stress disorder (PTSD) and may be nearing approval by the US Food and Drug Administration (FDA). 

According to Friederike Holze, PhD, psychopharmacologist at the University of Basel, in Switzerland, “there could be a place” for MDMA and psychedelics in treating chronic loneliness, but only under professional supervision. 

There would have to be clear guidelines too, says Joshua Woolley, MD, PhD, a psychiatrist at the University of California, San Francisco. 

MDMA and psychedelics “induce this plastic state, a state where people can change. They feel open, they feel like things are possible,” Dr. Woolley says. Then, with therapy, “you can help them change.”

Loneliness Can Impact Our Health

On top of the mental health ramifications, the physiologic effects of loneliness could have grave consequences over time. In observational studies, loneliness has been linked to higher risks for cancer and heart disease, and shorter lifespan. One third  of Americans over 45 say they are chronically lonely. 

Chronic loneliness changes how we think and behave, research shows. It makes us fear contact with others and see them in a more negative light, as more threatening and less trustworthy. Lonely people prefer to stand farther apart  from strangers and avoid touch. 

This is where MDMA-assisted therapies could potentially help, by easing these defensive tendencies, according to Dr. Woolley.

MDMA, Psychedelics, and Social Behavior

MDMA, or 3,4-methylenedioxymethamphetamine, is a hybrid  between a stimulant and a psychedelic. In Dr. de Wit’s earlier experiments, volunteers given MDMA engaged more in communal activities, chatting, and playing games. They used more positive words during social encounters than those who had received a placebo. And after MDMA, people felt less rejected if they were slighted in Cyberball  — a virtual ball-tossing game commonly used to measure the effects of social exclusion.

MDMA has been shown to reduce people’s response to other’s negative emotions, diminishing activation of the amygdala (the brain’s fear center) while looking at pictures of angry faces. 

This could be helpful. “If you perceive a person’s natural expression as being a little bit angry, if that disappears, then you might be more inclined to interact,” de Wit says. 

However, there may be downsides, too. If a drug makes people more trusting and willing to connect, they could be taken advantage of. This is why, Dr. Woolley says, “psychedelics have been used in cults.” 

MDMA may also make the experience of touch more pleasant. In a series of experiments in 2019, researchers gently stroked volunteers ’ arms with a goat-hair brush, mimicking the comforting gestures one may receive from a loved one. At the same time, the scientists monitored the volunteers’ facial muscles. People on MDMA perceived gentle touch as more pleasant than those on placebo, and their smile muscles activated more.

MDMA and psychedelics boost social behaviors in animals, too — suggesting that their effects on relationships have a biological basis. Rats on MDMA are more likely to lie next to each other, and mice become more resilient to social stress. Even octopuses become more outgoing after a dose of MDMA, choosing to spend more time with other octopuses instead of a new toy. Classic psychedelics show similar effects — LSD, for example, makes mice more social. 

Psychedelics can induce a sense of a “dissolution of the self-other boundary,” Dr. Woolley says. People who take them often say it’s “helped them feel more connected to themselves and other people.” LSD, first synthesized in 1938, may help increase empathy in some people. 

Psilocybin, a compound found in over 200 species of mushrooms and used for centuries in Mesoamerican rituals, also seems to boost empathy, with effects persisting for at least seven days. In Cyberball, the online ball-throwing game, people who took psilocybin felt less socially rejected, an outcome reflected in their brain activation patterns in one study — the areas responsible for social-pain processing appeared to dim after a dose. 

Making It Legal and Putting It to Use

In 2020, Oregon became the first state to establish a regulatory framework for psilocybin for therapeutic use, and  Colorado  followed suit in 2022. Such therapeutic applications of psilocybin could help fight loneliness as well, Dr. Woolley believes, because a “ common symptom of depression is that people feel socially withdrawn and lack motivation, ” he says. As mentioned above, MDMA-assisted therapy is also nearing FDA approval for PTSD. 

What remain unclear are the exact mechanisms at play. 

“MDMA releases oxytocin, and it does that through serotonin receptors,” Dr. de Wit says. Serotonin activates 5-HT1A receptors in the hypothalamus, releasing oxytocin into the bloodstream. In Dr. de Wit’s recent experiments, the more people felt connected after taking MDMA, the more oxytocin was found circulating in their bodies. (Another drug, methamphetamine, also upped the levels of oxytocin but did not increase feelings of connectedness.) 

“It’s likely that both something in the serotonin system independent of oxytocin, and oxytocin itself, contribute,” Dr. de Wit says. Dopamine, a neurotransmitter responsible for motivation, appears to increase as well. 

The empathy-boosting effects of LSD also seem to be at least partly driven by oxytocin, experiments published in 2021 revealed. Studies in mice, meanwhile, suggest that glutamate, a chemical messenger in the brain, may be behind some of LSD’s prosocial effects. 

Scientists are fairly certain which receptors these drugs bind to and which neurotransmitters they affect. “How that gets translated into these higher-order things like empathy and feeling connected to the world, we don’t totally understand,” Dr. Woolley says.

Challenges and the Future

Although MDMA and psychedelics are largely considered safe when taken in a legal, medically controlled setting, there is reason to be cautious.

“They have relatively low impact on the body, like heart rate increase or blood pressure increase. But they might leave some disturbing psychological effects,” says Dr. Holze. Scientists routinely screen experiment volunteers for their risk for psychiatric disorders. 

Although risk for addiction is low with both MDMA and psychedelics, there is always some risk for misuse. MDMA “ can produce feelings of well-being, and then people might use it repeatedly, ” Dr. de Wit says. “ That doesn ’ t seem to be a problem for really a lot of people, but it could easily happen. ”  

Still, possibilities remain for MDMA in the fight against loneliness. 

“[People] feel open, they feel like things are possible, they feel like they’re unstuck,” Dr. Woolley says. “You can harness that in psychotherapy.”

A version of this article appeared on Medscape.com.

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

HAMBURG, Germany — The human microbiome comprises 39 to 44 billion microbes. That is ten times more than the number of cells in our body. Hendrik Poeck, MD, managing senior physician of internal medicine at the University Hospital Regensburg, illustrated this point at the annual meeting of the German Society for Hematology and Medical Oncology. If the gut microbiome falls out of balance, then “intestinal dysbiosis potentially poses a risk for the pathogenesis of local and systemic diseases,” explained Dr. Poeck.

Cancers and their therapies can also be influenced in this way. “Microbial diversity affects whether a tumor grows, whether it leads to inflammation, immune escape mechanisms or genomic instability, or whether therapeutic resistances develop,” said Dr. Poeck.

Microbial diversity could be beneficial for cancer therapy, too. The composition of the microbiome varies significantly from host to host and can mutate. These properties make it a target for precision microbiotics, which involves using the gut microbiome as a biomarker to predict various physical reactions and to develop individualized diets.

Microbiome and Pathogenesis

The body’s microbiome fulfills a barrier function, especially where the body is exposed to an external environment: at the epidermis and the internal mucous membranes, in the gastrointestinal tract, and in the lungs, chest, and urogenital system.

Association studies on humans and experimental manipulations on mouse models of cancer showed that certain microorganisms can have either protective or harmful effects on cancer development, on the progression of a malignant disease, and on the response to therapy.

A Master Regulator?

Disruptions of the microbial system in the gut, as occur during antibiotic therapy, can have significant effects on a patient’s response to immunotherapy. Taking antibiotics shortly before or after starting therapy with immune checkpoint inhibitors (ICIs) significantly affected both overall survival (OS) and progression-free survival (PFS), as reported in a recent review and meta-analysis, for example.

Proton pump inhibitors also affect the gut microbiome and reduce the response to immunotherapy; this effect was demonstrated by an analysis of data from more than 2700 cancer patients that was recently presented at the annual meeting of the European Society for Medical Oncology (ESMO).

The extent to which the gut microbiome influences the efficacy of an ICI or predicts said efficacy was examined in a retrospective analysis published in Science in 2018, which Dr. Poeck presented. Resistance to ICI correlated with the relative frequency of the bacteria Akkermansia muciniphila in the gut of patients with cancer. In mouse models, the researchers restored the efficacy of the PD-1 blockade through a stool transplant.

Predicting Immunotherapy Response

If A muciniphila is present, can the composition of the microbiome act as a predictor for an effective ICI therapy?

Laurence Zitvogel, MD, PhD, and her working group at the National Institute of Health and Medical Research in Villejuif, France, performed a prospective study in 338 patients with non–small cell lung cancer and examined the prognostic significance of the fecal bacteria A muciniphila (Akk). The “Akkerman status” (low Akk vs high Akk) in a patient’s stool correlated with an increased objective response rate and a longer OS, independently of PD-L1 expression, antibiotics, and performance status. The OS for low Akk was 13.4 months, vs 18.8 months for high Akk in first-line treatment.

These results are promising, said Dr. Poeck. But there is no one-size-fits-all solution. No conclusions can be drawn from one bacterium on the efficacy of therapies in humans, since “the entirety of the bacteria is decisive,” said Dr. Poeck. In addition to the gut microbiome, the composition of gut metabolites influences the response to immunotherapies, as shown in a study with ICI.

Therapeutic Interventions

One possible therapeutic intervention to restore the gut microbiome is fecal microbiota transplantation (FMT). In a phase 1 study presented by Dr. Poeck, FMT was effective in the treatment of 20 patients with melanoma with ICI in an advanced and treatment-naive stage. Seven days after the patients received FMT, the first cycle with anti-PD-1 immunotherapy was initiated, with a total administration of three to four cycles. After 12 weeks, most patients were in complete or partial remission, as evidenced on imaging.

However, FMT also carries some risks. Two cases of sepsis with multiresistant Escherichia coli occurred, as well as other serious infections. Since then, there has been an FDA condition for extended screening of the donor stool, said Dr. Poeck. Nevertheless, this intervention is promising. A search of the keywords “FMT in cancer/transplant setting” reveals 46 currently clinical studies on clinicaltrials.gov.

Nutritional Interventions

Dr. Poeck advises caution about over-the-counter products. These products usually contain only a few species, such as Lactobacillus and Bifidobacterium. “Over-the-counter probiotics can even delay the reconstitution of the microbiome after antibiotics,” said Dr. Poeck, according to a study. In some studies, the response rates were significantly lower after probiotic intake or led to controversial results, according to Dr. Poeck.

In contrast, Dr. Poeck said prebiotics (that is, a fiber-rich diet with indigestible carbohydrates) were promising. During digestion, prebiotics are split into short-chain fatty acids by bacterial enzymes and promote the growth of certain microbiota.

In this way, just 20 g of extremely fiber-rich food had a significant effect on PFS in 128 patients with melanoma undergoing anti-PD-1 immunotherapy. With 20 g of fiber-rich food per day, the PFS was stable over 60 months. The most significant benefit was observed in patients with a sufficient fiber intake who were not taking probiotics.

What to Recommend?

In summary, Dr. Poeck said that it is important to “budget” well, particularly with antibiotic administration, and to strive for calculated therapy with as narrow a spectrum as possible. For patients who experience complications such as cytokine release syndrome as a reaction to cell therapy, delaying the use of antibiotics is important. However, it is often difficult to differentiate this syndrome from neutropenic fever. The aim should be to avoid high-risk antibiotics, if clinically justifiable. Patients should avoid taking antibiotics for 30 days before starting immunotherapy.

Regarding nutritional interventions, Dr. Poeck referred to the recent Onkopedia recommendation for nutrition after cancer and the 10 nutritional rules of the German Nutrition Society. According to Dr. Poeck, the important aspects of these recommendations are a fiber-rich diet (> 20 g/d) from various plant products and avoiding artificial sweeteners and flavorings, as well as ultraprocessed (convenience) foods. In addition, meat should be consumed only in moderation, and as little processed meat as possible should be consumed. In addition, regular (aerobic and anaerobic) physical activity is important.

“Looking ahead into the future,” said Dr. Poeck, “we need a uniform and functional understanding and we need a randomized prediction for diagnosis.”


This article was translated from the Medscape German edition.

A version of this article appeared on Medscape.com.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

Early diagnosis improves lung cancer survival. Yet in the general population, only 17% of cases are diagnosed at an early stage. Among veterans, that rises to more than 30%.

Despite the impact lung cancer screening (LCS) has on improving survival, screening rates in the US remain low. In November 2017, the US Department of Veterans Affairs (VA) issued a memorandum providing recommendations for LCS with low-dose computer tomography (CT) scans at VA facilities. The memorandum was updated July 2022. While the Office of the Inspector General (OIG) called the memoranda “guidelines,” it also stipulated to VA facilities that they may “only” perform LCS when they meet all 10 mandatory elements:  

• Standardized, evidence-based criteria for eligibility, frequency, and duration of LCS
• Processes to facilitate the identification of patients who meet VA LCS eligibility criteria
• Patient education materials and shared decision making for patients regarding participation in an LCS program
• Clinical LCS coordinator(s) to coordinate the care and management of patients in the program
• Access to an effective, evidence-based smoking cessation program
• An LCS program oversight board responsible for oversight of the program’s conduct and management
• Access to a multidisciplinary lung nodule management board with clinical expertise in lung nodule management and diagnostic pathways
• Access to a tumor board with expertise in lung cancer treatment
• Optimized radiology CT protocols and standardized procedure names, along with standardized reporting methodology/codes and lung nodule management guidelines
• A patient management tool/registry to rigorously track and manage patients to ensure high levels of adherence to LCS management guidelines

However, in a recent investigation, the OIG found that facility staff involved in LCS reported that VA LCS guideline requirements “presented barriers to broader adoption of LCS” and did not ensure consistent implementation.

One problem, the OIG found, was the limited use of LCS at VA facilities. Just over half of the surveyed VA facilities reported having an established LCS program consistent with VA guidelines for LCS in 2022. There were also barriers to implementing LCS program requirements, such as the absence of an LCS coordinator, the lack of adequate staffing, the absence of a patient registry, and the lack of a multidisciplinary board.

Another problem was the inconsistent implementation of screening. Facilities with LCS programs reported varied use of program elements, including inconsistent use of an LCS coordinator to manage patients in the program.

The OIG also found that regardless of whether facilities had established an adherent LCS program, they varied in how they identified screening-eligible patients. The VA National Center for LCS recommends the use of clinical reminders as the preferred method to identify patients—but it is not required and not all facilities use it. The clinical reminder, the OIG report points out, can capture accurate smoking history information within the electronic health record to support identifying patients meeting LCS criteria.

The facilities also varied in their methods for interpreting low-dose CT scans. Ten sites, for instance, reported not using an established system for the classification of the results. The OIG notes that this could lead to inaccurate interpretation of the low-dose CT scan results and increase the risk for patient harm and health care costs.

The OIG made the following 3 recommendations to the Under Secretary for Health: (1) Review the operational memorandum for lung cancer screening implementation and assess whether LCS rates could be enhanced by allowing a facility to conduct LCS while developing all mandated elements; (2) Review the operational memorandum for LCS implementation and assess whether LCS rates could be enhanced by reevaluating, prioritizing, and clarifying the mandated elements; and (3) Consider mandating eligible patients be offered LCS consistent with other required cancer screenings in the VA.

The Under Secretary for Health concurred with the recommendations and provided an acceptable action plan. The OIG will follow up on the planned actions until they are completed.

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

Family members of veterans exposed to contaminated drinking water at Marine Corps Base Camp Lejeune, Jacksonville, North Carolina, from August 1, 1953, to December 31, 1987, are now eligible for reimbursement of health care costs associated with Parkinson disease (PD) under the Camp Lejeune Family Member Program, the US Department of Veterans Affairs (VA) has announced.

That brings the number of illnesses or conditions those family members can be reimbursed for to 16: esophageal, lung, breast, bladder, and kidney cancer, leukemia, multiple myeloma, renal toxicity, miscarriage, hepatic steatosis, female infertility, myelodysplastic syndromes, scleroderma, neurobehavioral effects, non-Hodgkin lymphoma, and Parkinson disease.

A recent JAMA study of 340,489 service members found that the risk of PD is 70% higher for veterans stationed at Camp Lejeune (n = 279) compared with veterans stationed at Camp Pendleton, California (n = 151).

The researchers say water supplies at Camp Lejeune were contaminated with several volatile organic compounds. They suggest that the risk of PD may be related to trichloroethylene exposure (TCE), a volatile organic compound widely used as a cleaning agent, in the manufacturing of some refrigerants, and found in paints and other products. In January, the US Environmental Protection Agency issued a revised risk determination saying that TCE presents an unreasonable risk to the health of workers, occupational nonusers (workers nearby but not in direct contact with this chemical), consumers, and bystanders.

Levels at Camp Lejeune were highest for TCE, with monthly median values greater than 70-fold the permissible amount.

Camp Lejeune veterans also had a significantly increased risk of prodromal PD diagnoses, including tremor, anxiety, and erectile dysfunction, and higher cumulative prodromal risk scores. No excess risk was found for other forms of neurodegenerative parkinsonism.

The PACT Act allows veterans and their families to file lawsuits for harm caused by exposure to contaminated water at Camp Lejeune. “Veterans and their families deserve no-cost health care for the conditions they developed due to the contaminated water at Camp Lejeune,” said VA’s Under Secretary for Health, Dr. Shereef Elnahal, MD. “We’re proud to add Parkinson disease to the list of conditions that are covered for veteran family members, and we implore anyone who may be living with this disease—or any of the other conditions covered by VA’s Camp Lejeune Family Member Program—to apply for assistance today.”

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

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

The average physician makes $352,000, and some earn well into the $500,000s. So, doctors don’t have to worry about money, right?

You know the answer to that.

One thing all physicians have in common about money, says James M. Dahle, MD, FACEP, founder of The White Coat Investor, is that they don’t receive any training in business, personal finance, or investing throughout their schooling or careers unless they seek it out. This leaves many unprepared to make the best investing and money-saving decisions, while others get too frustrated about their lack of knowledge to even dip their toe into the investing pool.

Exhibit A: Four out of 10 physicians have a net worth below $1 million, according to the Medscape Physician Wealth & Debt Report 2023. Elizabeth Chiang, MD, PhD, an oculoplastic surgeon and a physician money coach at Grow Your Wealthy Mindset, notes that many of those doctors are over age 65, “which means they essentially can’t retire.”

And that’s just one pain point.

Physicians have money concerns specific to their profession and background. Luckily, some fellow doctors also serve as financial and wealth advisors just for other doctors. We sought out a few to get their advice--and fixes--for common physician blind spots.

Blind Spot #1

The early lean years skew doctors’ money outlook. “We have an extended training period, which commonly consists of taking on a large amount of debt, followed by 3 to 8 years of being paid a modest salary, and then finally a large boost in income,” explains Dr. Chiang. This can lay a shaky foundation for the earning years to come, and as a result, a lot of doctors just don’t think about money in healthy ways. Once their incomes increase, physicians may be surprised, for example, that making a multiple six-figure salary means paying six figures in taxes.

The Fix

Treat financial health like physical health. That means money cannot be a taboo subject. “The misguided mindset is that we didn’t become physicians to make money, we did it to help people,” explains Jordan Frey, MD, creator of the blog, The Prudent Plastic Surgeon.

Dr. Frey acknowledges that the desire to help is certainly true. But the result is a false idea that “to think about our personal finances makes us a worse doctor.”

Blind Spot #2

Because doctors know a lot about one thing (medicine), they might assume they know a lot about everything (such as investing). “Totally different fields with a different language and different way to think about it,” Dahle explains. This overconfidence could lead to some negligent or risky financial decisions.

The Fix

Educate yourself. There are several books on personal finance and investing written by physicians for physicians. Dr. Chiang recommends The Physician Philosopher’s Guide to Personal Finance, by James Turner, MD; Financial Freedom Rx, by Chirag Shah, MD, and Jayanth Sridhar, MD; and The Physician’s Guide to Finance, by Nicholas Christian and Amanda Christian, MD. There are also podcasts, blogs, and courses to help educate doctors on finance, such as the Fire Your Financial Advisor course by The White Coat Investor.

Blind Spot #3

Undersaving. Retirement saving is one thing, but 24% of doctors say they don’t even put money away in a taxable savings account, according to the Wealth & Debt Report.

Cobin Soelberg, MD, JD, a board-certified anesthesiologist and founder and principal advisor with Greeley Wealth Management, is the treasurer of his anesthesiology group. “I get to see every month how much people are saving, and even on an anesthesiologist salary, where everyone’s making about $400,000 a year, a lot of people are not saving anything, which is crazy.”

Undersaving can be both a time issue and a mindset one.

Time: Doctors often start investing in their retirement accounts later than the average professional, says Dr. Chiang. “A lot of physicians will max out their 401k or 403b,” she explains. “But if you’re putting in $20,000 a year and only starting when you’re in your early 30s, that’s not enough to get you to retirement.”

Mindset: Doctors also see people of all ages who are sick, dying, and injured. “They all know someone who worked hard and saved and then dropped dead at 55,” explains Dr. Dahle. This, he says, can lead to a bit of a “you only live once” attitude that prioritizes spending over saving.

The Fix

Shoot for 20%. If you can’t save 20% of your gross now, strive to get to that point. Think of it as telling a patient they have to change their behavior or trouble will come - not if, but when. “Develop a written investing plan and then stick with it through thick and thin,” says Dr. Dahle. “Once you have a reasonable plan, all you have to do is fund it adequately by saving 20% of your gross income, and a doctor will easily retire as a multimillionaire.”

Blind Spot #4

Bad investment strategies. Thirty-six percent of doctors experience their largest financial losses from lousy investments, according to the Wealth & Debt Report. Meanwhile, 17% of PCPs and 12% of specialists say they haven’t made any investments at all. That’s a terrible mix of doing the wrong thing and doing a worse thing.

The Fix

Don’t overthink investing, but don’t underthink it either. “As high-income earners, doctors just don’t need to take this high level of risk to reach their financial goals,” Dr. Frey says. A good investment plan doesn’t require you to time the stock market or predict individual stock winners. Consider what Vanguard founder Jack Bogle once said about investing: “Be bored by the process but elated by the outcome.”

Dr. Frey suggests going super-simple: index funds. Ignore investing strategies with actively managed mutual funds or individual stocks, as well as risky alternative investments such as cryptocurrency and angel investments. Everyone assumes doctors have money to burn, and they will push sketchy investment ideas at them. Avoid.

Blind Spot #5

Not taking debt seriously enough. The average medical student debt is $250,000 and can exceed $500,000, says Dr. Soelberg. Many doctors spend the first 10 to 20 years of their careers paying this off. Today’s graduates are paying more than 7% on their loans.

And it’s not just student debt: 39% of physicians carry five or more credit cards, and 34% have mortgages larger than $300,000 (with half of those are more than than $500K), per the Wealth & Debt Report.

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