The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.

ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.¹ These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.

The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.

Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.

Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.

ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.¹ These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.

The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.

Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.

Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The gradual development of a rash in an area of frequent direct contact between metal and skin is pathognomonic for allergic contact dermatitis (ACD). Contact dermatitis often results from exposure to metals. Stainless steel is a group of ferrous alloys composed of a variety of elements including nickel, which is added to increase corrosion resistance. Unfortunately, nickel is a metal commonly known to induce a delayed hypersensitivity response. In the upper left corner of the image shown here, one can see the metal plate of the watch band.

ACD is a T-cell mediated, delayed, type IV hypersensitivity response to foreign materials.¹ These reactions typically occur around 48 to 72 hours following contact with the metal but can take weeks to appear, depending on the amount of T-cell activation. Symptoms may appear more rapidly on repeat exposures. Lesions manifest as erythematous, scaly plaques, which may include vesicles and bullae in severe cases.

The mainstay of treatment for allergic contact dermatitis is avoidance of the allergen once it has been identified. Nickel is commonly found in metal parts on clothing and in jewelry. One method of protection from nickel in these cases is to cover the metal that touches the skin with a clear nail polish or another clear barrier (commercial options are available). Duct tape or fabric can also be used to cover the metal.

Topical corticosteroids are the first-line therapy to treat lesions. Topical calcineurin inhibitors are an alternative. Systemic corticosteroids may be indicated if there is extensive body surface area involvement. Phototherapy or systemic immunosuppression may be considered in severe refractory cases.

Our patient was counseled on the nature of the disease process and educated on strategies to avoid future exposures. Treatment was initiated with topical triamcinolone 0.1% ointment with follow-up as needed.

‌

Image courtesy of Daniel Stulberg, MD. Text courtesy of Spenser Squire, MD, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

Many older adults with epilepsy are misdiagnosed even though the highest incidence of the disease is in people over 75, a neurologist told an audience at the annual meeting of the American Epilepsy Society. She urged colleagues to focus on possible interactions with other neurological conditions, consider various complicating factors, and embrace a team strategy.

“There are lots of nuances,” said Rebecca O’Dwyer, MD, an adult epilepsy specialist with Rush Epilepsy Center in Chicago. “It takes a lot of time and requires a multidisciplinary approach. Taking care of older individuals with epilepsy truly is a team sport.”

According to a 2014 report highlighted by Dr. O’Dwyer, “nearly 25% of new-onset seizures occur after age 65. The incidence of epilepsy in this age group is almost twice the rate in children, and in people over age 80, it is triple the rate in children.”

Research suggests it can take up to 2 years to correctly diagnose epilepsy in older people, Dr. O’Dwyer said, and nearly two-thirds of cases may be misdiagnosed. “Some of it is just limited awareness. There’s this perception in the public that epilepsy is something that occurs in younger adults or young children, and that when you come to a certain age, you cannot have epilepsy. Also, there are differences in the clinical manifestations of their seizures, and many comorbid possibilities could also present in similar fashion to epilepsy. Some of our usual tools that we use to come to the diagnosis such as EEG are also known to be less sensitive in this age group.”

According to the 2014 report, research finds that the elderly are much more likely than young adults to have postictal sleepiness or unresponsiveness and seizures manifesting as brief moments of subtle confusion. They’re much less likely to have epileptic aura and generalized tonic seizures.

“An epileptic seizure in an older adult tends to be less dramatic with fewer motor manifestations, and they often tend to be monophasic. They may be so subtle that they’re missed by family members and other medical providers,” Dr. O’Dwyer said. “I had a patient whose seizure consisted of her tapping her left shoulder. She had been doing this for at least 6 months, and she came to my clinic after her daughter realized that she was a little confused afterward. She’d already seen a behavioral neurologist and been given the diagnosis of dementia. We were fortunate enough to catch one of these episodes while we were doing an EEG, and we diagnosed her with focal epilepsy. With one antiseizure medication, we stopped the seizures, and her memory came back.”

Make sure to take detailed histories and keep an eye out for descriptions of behaviors that are episodic but perhaps not typical of seizures, she said.

Epilepsy can be misdiagnosed as a variety of conditions, she said, such as syncope, Alzheimer’s disease, stroke, Parkinson’s disease, and atrial fibrillation. “When you do diagnose somebody older with new-onset epilepsy, you should work them up for a stroke. Because we know that within the first 4 weeks after their first seizure the likelihood that they could have a stroke is three times higher.”

It’s also possible that neurological conditions can be followed by new-onset epilepsy, she said, making dementia even worse. Low-dose antiepileptic drugs can be helpful in these patients.

But seniors are especially vulnerable to side effects of antiepileptic drugs such as sedation, dizziness, and cardiac-conduction abnormalities. “You must adhere to the mantra of going low and going slow because they are exquisitely susceptible,” Dr. O’Dwyer said.

She recommends lamotrigine, which is well tolerated with helpful mood-stabilizing effects, and levetiracetam, which attenuates cognitive decline in dementia but may cause side effects such as irritable mood. Zonisamide is showing promise in patients with parkinsonian syndromes, she said, and it may be helpful to maximize drugs that patients are already taking such as gabapentin or pregabalin.

Finally, Dr. O’Dwyer urged colleagues to work in teams that include caregivers, primary care doctors, social workers, and pharmacists. “Sometimes in all this,” she said, “my job is the easiest.”

Dr. O’Dwyer discloses research support from the Shapiro Foundation.

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

The Food and Drug Administration on Dec. 22, 2021, granted emergency use authorization (EUA) for a new antiviral pill to treat people with symptomatic COVID-19.

Pfizer’s ritonavir, name brand Paxlovid, can now be taken by patients ages 12 and up who weigh at least 88 pounds.

The antiviral is only for people who test positive for the coronavirus and who are at high risk for severe COVID-19, including hospitalization or death. It is available by prescription only and should be taken as soon as possible after diagnosis and within 5 days of the start of symptoms.

Paxlovid is taken as three tablets together orally twice a day for 5 days, for a total of 30 tablets.

Possible side effects include a reduced sense of taste, diarrhea, high blood pressure, and muscle aches.

The authorization arrives as U.S. cases of the Omicron variant are surging, some monoclonal antibody treatments are becoming less effective, and Americans struggle to maintain some sense of tradition and normalcy around the holidays.

Paxlovid joins remdesivir as an available antiviral to treat COVID-19. Remdesivir is fully approved by the FDA but is given only intravenously in a hospital.  

The COVID-19 antiviral pills come with some obvious advantages, including greater convenience for consumers – such as home use – and the potential to expand treatment for people in low- and middle-income countries.

‘An exciting step forward’

The EUA for Pfizer’s new drug has been highly anticipated, and news of its impending authorization circulated on social media on Tuesday. Eric Topol, MD, called the development an “exciting step forward.” Dr. Topol is editor in chief of Medscape, the parent company of MDedge.

He and many others also expected the FDA to grant emergency use authorization for an antiviral from Merck. But there was no immediate word Wednesday if that was still going to happen.

An accelerated authorization?

The FDA’s authorization for Pfizer’s antiviral comes about 5 weeks after the company submitted an application to the agency. In its submission, the company said a study showed the pill reduced by 89% the rate of hospitalization and death for people with mild to moderate COVID-19 illness.

In April 2021, Pfizer announced its antiviral pill for COVID-19 could be available by year’s end. In September, an official at the National Institutes of Allergy and Infectious Diseases seconded the prediction.

Merck filed its EUA application with the FDA in October. The company included results of its phase 3 study showing the treatment was linked to a 50% reduction in COVID-19 hospitalizations.

Interestingly, in September, Merck announced the findings of laboratory studies suggesting that molnupiravir would work against variants of the coronavirus because the agent does not target the virus’s spike protein. At the time, Delta was the dominant variant in the United States.

Faith-based purchasing

The U.S. government has already recognized the potential of these oral therapies, at least in terms of preorders.

Last month, it announced intentions to purchase $1 billion worth of Merck’s molnupiravir, adding to the $1.2 billion worth of the pills the U.S. ordered in June 2021. Also in November, the government announced it would purchase 10 million courses of the Pfizer pill at an estimated cost of $5.3 billion.

The government preorders of the antiviral pills for COVID-19 are separate from the orders for COVID-19 vaccines. Most recently, the Biden administration announced it will make 500 million tests for coronavirus infection available to Americans for free in early 2022.

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

Margin marking before endoscopic mucosal resection (EMR) of large colorectal polyps cut the risk of recurrence by 80% when compared with traditional EMR, new data suggest.

A team of researchers, led by Dennis Yang, MD, with the Center for Interventional Endoscopy at AdventHealth, Orlando, compared polyp recurrence after patients received EMR with margin marking versus recurrence after conventional EMR in a historical control group. They conclude that the simple margin-marking strategy may offer an alternative to margin ablation.

The findings of the study were published online Nov. 29 in Gastrointestinal Endoscopy.

A single-center, historical control study

A total of 210 patients (average age, 66 years; 56.2% women) with 210 polyps (average size, 30 mm; interquartile range: 25-40 mm) had either EMR with margin marking (EMR-MM; n = 74) or conventional EMR (n = 136). The groups had similar patient and lesion characteristics.

For EMR-MM, cautery marks were drawn along the lateral margins of the polyp with the snare tip. EMR followed with resection of the healthy mucosa with the marks.

Physicians can confirm complete resection, including a healthy margin, when no cautery marks are visible after EMR, the authors write.

A follow-up colonoscopy was performed 3 to 6 months later, the results of which were compared against historical controls.

After 6 months, EMR-MM led to a lower recurrence rate compared with the historical control group with traditional EMR (8% vs. 29%, respectively; P < .001).

“This strategy allowed a more reliable wide-field EMR, which may account for why our preliminary results demonstrated an 80% reduction in the likelihood of recurrence even after controlling for other factors, including polyp size and histopathology,” the authors write.

Recurrence risk has been one of the main limitations of EMR compared with surgery, with rates from 10%-35%, the authors note, though it has fewer adverse reactions and offers better quality of life than surgery.

Dr. Yang told this news organization that multiple studies have looked at possible factors for recurrence, which is thought to primarily occur at the lateral resection margins of the polyp.

“That’s based on recent data that has shown that burning the resection margins after you actually take the lesion out reduces recurrence,” he said. “What that indirectly implies is that whenever we resect something, we may think we’ve got the entire lesion at the lateral margins, but we don’t.”

As Dr. Yang described, it was this implication that led to the premise of the study.

“If we were to somehow put visible marks outside the margins of the lesion, the marks would serve as visible cues to tell us how much more tissue we needed to resect and thereby help us get a more reliable way of ensuring clean resection margins.”

Dr. Yang and colleagues also found that EMR-MM was not linked with an increase in adverse events. On multivariable analysis, EMR-MM was the main predictor of recurrence (odds ratio, 0.20; 95% CI, 0.13-0.64; P = .003) aside from polyp size (OR, 2.81; 95% CI, 1.35-6.01; P = .008).

Expert: standard of care likely still better

Gastroenterologist Douglas Rex, MD, Distinguished Professor Emeritus of Medicine at Indiana University School of Medicine, Indianapolis, who was not involved in the study, told this news organization that he is not convinced that it is necessary or wise to use the margin-marking technique described in the paper over the current standard of care.

Dr. Rex explained that presently, physicians inject large lesions submucosally with fluid colored for contrast to delineate the margin of the polyp. This raises the question: if you can see the lesion well with that method, do you need to place the marks before you start around the border on the normal mucosa, as they did for the margin-marking group in this study?

Dr. Rex also noted that the researchers’ 29% control group recurrence rate is relatively high.

“Most of the evidence – if you look at the big meta-analyses – suggests that the recurrence rate with traditional methods is around 15%,” he said.

He added that even the recurrence rate in the current study’s active treatment arm is much higher than the 2%-5% rate seen in recent thermal ablation trials by Klein and colleagues and Sidhu and colleagues, both published in Gastroenterology.

“The methods described in those two papers should be considered the current standard of care,” Dr. Rex said. “Neither one of those involves this [margin-marking] method.”

Dr. Yang agrees that the Klein and Sidhu trials represent the standard of care, but he says it’s important to note that the 2% recurrence may not represent the actual practice of endoscopists of all skill levels.

“These are highly controlled studies coming from very experienced endoscopists,” he said.

“Our data are not trying to supplant what the high-quality studies on thermal ablation have shown. The point is to show that this is a concept that could potentially help,” he said.

“What I’m proposing is a potential alternative that could be better than that. Obviously, we won’t know until a comparative type of trial is performed.”

On that point, Dr. Yang and Dr. Rex agree.

Dr. Rex said that a randomized control trial would clarify some points and be useful to compare margin marking directly with the current standard of care, “which is to remove the whole thing and then burn up the margin.”

“Based on what we have seen so far, I would predict the current standard of care would have a very good chance of winning in terms of efficacy, because it’s hard to get lower than 2% [recurrence],” he said. “And it might well win with regard to safety, because burning the margin is at least theoretically safer than what they’re doing here.”

Dr. Rex said margin marking may be beneficial with the form of EMR that does not involve submucosal injection: underwater EMR. In underwater EMR, there’s no submucosal injection, and some people will mark the margin in those instances, he said.

“I do think it’s reasonable to do margin marking for underwater EMR,” Dr. Rex said.

Dr. Yang is a consultant for Boston Scientific, Olympus, Lumendi, and Steris. A coauthor is a consultant for Olympus, Boston Scientific, Cook Medical, Merit, Microtech, Steris, Lumendi, and Fujifilm. Another coauthor receives research grants from Steris and Cosmo/Aries Pharmaceuticals. Dr. Rex disclosed no relevant financial relationships.

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

Margin marking before endoscopic mucosal resection (EMR) of large colorectal polyps cut the risk of recurrence by 80% when compared with traditional EMR, new data suggest.

A team of researchers, led by Dennis Yang, MD, with the Center for Interventional Endoscopy at AdventHealth, Orlando, compared polyp recurrence after patients received EMR with margin marking versus recurrence after conventional EMR in a historical control group. They conclude that the simple margin-marking strategy may offer an alternative to margin ablation.

The findings of the study were published online Nov. 29 in Gastrointestinal Endoscopy.

A single-center, historical control study

A total of 210 patients (average age, 66 years; 56.2% women) with 210 polyps (average size, 30 mm; interquartile range: 25-40 mm) had either EMR with margin marking (EMR-MM; n = 74) or conventional EMR (n = 136). The groups had similar patient and lesion characteristics.

For EMR-MM, cautery marks were drawn along the lateral margins of the polyp with the snare tip. EMR followed with resection of the healthy mucosa with the marks.

Physicians can confirm complete resection, including a healthy margin, when no cautery marks are visible after EMR, the authors write.

A follow-up colonoscopy was performed 3 to 6 months later, the results of which were compared against historical controls.

After 6 months, EMR-MM led to a lower recurrence rate compared with the historical control group with traditional EMR (8% vs. 29%, respectively; P < .001).

“This strategy allowed a more reliable wide-field EMR, which may account for why our preliminary results demonstrated an 80% reduction in the likelihood of recurrence even after controlling for other factors, including polyp size and histopathology,” the authors write.

Recurrence risk has been one of the main limitations of EMR compared with surgery, with rates from 10%-35%, the authors note, though it has fewer adverse reactions and offers better quality of life than surgery.

Dr. Yang told this news organization that multiple studies have looked at possible factors for recurrence, which is thought to primarily occur at the lateral resection margins of the polyp.

“That’s based on recent data that has shown that burning the resection margins after you actually take the lesion out reduces recurrence,” he said. “What that indirectly implies is that whenever we resect something, we may think we’ve got the entire lesion at the lateral margins, but we don’t.”

As Dr. Yang described, it was this implication that led to the premise of the study.

“If we were to somehow put visible marks outside the margins of the lesion, the marks would serve as visible cues to tell us how much more tissue we needed to resect and thereby help us get a more reliable way of ensuring clean resection margins.”

Dr. Yang and colleagues also found that EMR-MM was not linked with an increase in adverse events. On multivariable analysis, EMR-MM was the main predictor of recurrence (odds ratio, 0.20; 95% CI, 0.13-0.64; P = .003) aside from polyp size (OR, 2.81; 95% CI, 1.35-6.01; P = .008).

Expert: standard of care likely still better

Gastroenterologist Douglas Rex, MD, Distinguished Professor Emeritus of Medicine at Indiana University School of Medicine, Indianapolis, who was not involved in the study, told this news organization that he is not convinced that it is necessary or wise to use the margin-marking technique described in the paper over the current standard of care.

Dr. Rex explained that presently, physicians inject large lesions submucosally with fluid colored for contrast to delineate the margin of the polyp. This raises the question: if you can see the lesion well with that method, do you need to place the marks before you start around the border on the normal mucosa, as they did for the margin-marking group in this study?

Dr. Rex also noted that the researchers’ 29% control group recurrence rate is relatively high.

“Most of the evidence – if you look at the big meta-analyses – suggests that the recurrence rate with traditional methods is around 15%,” he said.

He added that even the recurrence rate in the current study’s active treatment arm is much higher than the 2%-5% rate seen in recent thermal ablation trials by Klein and colleagues and Sidhu and colleagues, both published in Gastroenterology.

“The methods described in those two papers should be considered the current standard of care,” Dr. Rex said. “Neither one of those involves this [margin-marking] method.”

Dr. Yang agrees that the Klein and Sidhu trials represent the standard of care, but he says it’s important to note that the 2% recurrence may not represent the actual practice of endoscopists of all skill levels.

“These are highly controlled studies coming from very experienced endoscopists,” he said.

“Our data are not trying to supplant what the high-quality studies on thermal ablation have shown. The point is to show that this is a concept that could potentially help,” he said.

“What I’m proposing is a potential alternative that could be better than that. Obviously, we won’t know until a comparative type of trial is performed.”

On that point, Dr. Yang and Dr. Rex agree.

Dr. Rex said that a randomized control trial would clarify some points and be useful to compare margin marking directly with the current standard of care, “which is to remove the whole thing and then burn up the margin.”

“Based on what we have seen so far, I would predict the current standard of care would have a very good chance of winning in terms of efficacy, because it’s hard to get lower than 2% [recurrence],” he said. “And it might well win with regard to safety, because burning the margin is at least theoretically safer than what they’re doing here.”

Dr. Rex said margin marking may be beneficial with the form of EMR that does not involve submucosal injection: underwater EMR. In underwater EMR, there’s no submucosal injection, and some people will mark the margin in those instances, he said.

“I do think it’s reasonable to do margin marking for underwater EMR,” Dr. Rex said.

Dr. Yang is a consultant for Boston Scientific, Olympus, Lumendi, and Steris. A coauthor is a consultant for Olympus, Boston Scientific, Cook Medical, Merit, Microtech, Steris, Lumendi, and Fujifilm. Another coauthor receives research grants from Steris and Cosmo/Aries Pharmaceuticals. Dr. Rex disclosed no relevant financial relationships.

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

Margin marking before endoscopic mucosal resection (EMR) of large colorectal polyps cut the risk of recurrence by 80% when compared with traditional EMR, new data suggest.

A team of researchers, led by Dennis Yang, MD, with the Center for Interventional Endoscopy at AdventHealth, Orlando, compared polyp recurrence after patients received EMR with margin marking versus recurrence after conventional EMR in a historical control group. They conclude that the simple margin-marking strategy may offer an alternative to margin ablation.

The findings of the study were published online Nov. 29 in Gastrointestinal Endoscopy.

A single-center, historical control study

A total of 210 patients (average age, 66 years; 56.2% women) with 210 polyps (average size, 30 mm; interquartile range: 25-40 mm) had either EMR with margin marking (EMR-MM; n = 74) or conventional EMR (n = 136). The groups had similar patient and lesion characteristics.

For EMR-MM, cautery marks were drawn along the lateral margins of the polyp with the snare tip. EMR followed with resection of the healthy mucosa with the marks.

Physicians can confirm complete resection, including a healthy margin, when no cautery marks are visible after EMR, the authors write.

A follow-up colonoscopy was performed 3 to 6 months later, the results of which were compared against historical controls.

After 6 months, EMR-MM led to a lower recurrence rate compared with the historical control group with traditional EMR (8% vs. 29%, respectively; P < .001).

“This strategy allowed a more reliable wide-field EMR, which may account for why our preliminary results demonstrated an 80% reduction in the likelihood of recurrence even after controlling for other factors, including polyp size and histopathology,” the authors write.

Recurrence risk has been one of the main limitations of EMR compared with surgery, with rates from 10%-35%, the authors note, though it has fewer adverse reactions and offers better quality of life than surgery.

Dr. Yang told this news organization that multiple studies have looked at possible factors for recurrence, which is thought to primarily occur at the lateral resection margins of the polyp.

“That’s based on recent data that has shown that burning the resection margins after you actually take the lesion out reduces recurrence,” he said. “What that indirectly implies is that whenever we resect something, we may think we’ve got the entire lesion at the lateral margins, but we don’t.”

As Dr. Yang described, it was this implication that led to the premise of the study.

“If we were to somehow put visible marks outside the margins of the lesion, the marks would serve as visible cues to tell us how much more tissue we needed to resect and thereby help us get a more reliable way of ensuring clean resection margins.”

Dr. Yang and colleagues also found that EMR-MM was not linked with an increase in adverse events. On multivariable analysis, EMR-MM was the main predictor of recurrence (odds ratio, 0.20; 95% CI, 0.13-0.64; P = .003) aside from polyp size (OR, 2.81; 95% CI, 1.35-6.01; P = .008).

Expert: standard of care likely still better

Gastroenterologist Douglas Rex, MD, Distinguished Professor Emeritus of Medicine at Indiana University School of Medicine, Indianapolis, who was not involved in the study, told this news organization that he is not convinced that it is necessary or wise to use the margin-marking technique described in the paper over the current standard of care.

Dr. Rex explained that presently, physicians inject large lesions submucosally with fluid colored for contrast to delineate the margin of the polyp. This raises the question: if you can see the lesion well with that method, do you need to place the marks before you start around the border on the normal mucosa, as they did for the margin-marking group in this study?

Dr. Rex also noted that the researchers’ 29% control group recurrence rate is relatively high.

“Most of the evidence – if you look at the big meta-analyses – suggests that the recurrence rate with traditional methods is around 15%,” he said.

He added that even the recurrence rate in the current study’s active treatment arm is much higher than the 2%-5% rate seen in recent thermal ablation trials by Klein and colleagues and Sidhu and colleagues, both published in Gastroenterology.

“The methods described in those two papers should be considered the current standard of care,” Dr. Rex said. “Neither one of those involves this [margin-marking] method.”

Dr. Yang agrees that the Klein and Sidhu trials represent the standard of care, but he says it’s important to note that the 2% recurrence may not represent the actual practice of endoscopists of all skill levels.

“These are highly controlled studies coming from very experienced endoscopists,” he said.

“Our data are not trying to supplant what the high-quality studies on thermal ablation have shown. The point is to show that this is a concept that could potentially help,” he said.

“What I’m proposing is a potential alternative that could be better than that. Obviously, we won’t know until a comparative type of trial is performed.”

On that point, Dr. Yang and Dr. Rex agree.

Dr. Rex said that a randomized control trial would clarify some points and be useful to compare margin marking directly with the current standard of care, “which is to remove the whole thing and then burn up the margin.”

“Based on what we have seen so far, I would predict the current standard of care would have a very good chance of winning in terms of efficacy, because it’s hard to get lower than 2% [recurrence],” he said. “And it might well win with regard to safety, because burning the margin is at least theoretically safer than what they’re doing here.”

Dr. Rex said margin marking may be beneficial with the form of EMR that does not involve submucosal injection: underwater EMR. In underwater EMR, there’s no submucosal injection, and some people will mark the margin in those instances, he said.

“I do think it’s reasonable to do margin marking for underwater EMR,” Dr. Rex said.

Dr. Yang is a consultant for Boston Scientific, Olympus, Lumendi, and Steris. A coauthor is a consultant for Olympus, Boston Scientific, Cook Medical, Merit, Microtech, Steris, Lumendi, and Fujifilm. Another coauthor receives research grants from Steris and Cosmo/Aries Pharmaceuticals. Dr. Rex disclosed no relevant financial relationships.

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

GI, liver, and pancreatic diseases cost the U.S. health care system about $120B per year and account for approximately 250,000 annual deaths, according to a “conservative” estimate from a recent analysis.

These figures emphasize the need for more research funding in the area, along with additional clinical and public health initiatives, reported lead author Anne F. Peery, MD, of the University of North Carolina School of Medicine, Chapel Hill, and colleagues.

“Reports detailing the burden of GI diseases are necessary for clinical research, decision making, and priority setting,” the investigators wrote in Gastroenterology. “Our aim was to describe health care use, expenditures, and research funding across GI, liver, and pancreatic diseases in the United States.”

Dr. Peery and colleagues analyzed data from 14 sources, including the National Institutes of Health; the Centers for Disease Control and Prevention; the National Ambulatory Medical Care Survey; and others. GI-specific outcomes included mortality, readmissions, hospitalizations, office-based visits, and emergency department visits. The investigators also characterized trends in cancers, organ transplants, and GI endoscopy, as well as GI-specific health care costs and NIH research funding. Annual findings were presented for various periods.

Total GI health care spending was $119.6 billion in 2018, down from $135.9 billion in 2015. The top five most costly conditions were biliary tract diseases ($16.9 billion), esophageal disorders ($12.1 billion), abdominal pain ($9.5 billion), abdominal hernias ($9.0 billion), and diverticular disease ($9.0 billion). The investigators noted that medication costs were particularly high for two categories: inflammatory bowel diseases and esophageal disorders, which had prescription drug costs relative to total expenditures of 71% and 53%, respectively.

“This conservative estimate [of $119.6 billion] did not include most GI cancers and likely underestimated the costs associated with some GI conditions,” the investigators noted. “For example, the Medical Expenditure Panel Survey estimate associated with GI bleeding was $300 million. In comparison, the aggregate cost of GI bleeding was more realistically $3.7 billion, as estimated using inpatient data from the National Inpatient Sample.”

In 2016, the most common GI-related diagnosis in the U.S. was abdominal pain (15.7 million annual visits), followed by nausea and vomiting (5.0 million visits), gastroesophageal reflux disorder and reflux esophagitis (4.7 million visits), constipation (3.1 million visits), and abdominal wall/inguinal hernia (2.8 million visits).

The top three most common GI-related hospital admissions in 2018 were GI bleeding (1.3 million admissions), followed by cholelithiasis and cholecystitis (741,060 admissions), then pancreatitis (685,880 admissions). GI bleeding was also the leading cause of 30-day readmission in 2018 (84,533 readmissions).

“We found substantial numbers of GI conditions and symptoms listed in secondary positions on the discharge record,” the investigators wrote. “For example, liver disease accounted for 280,645 discharges with a primary diagnosis; however, there were 13-fold as many discharges (3.6 million in 2018) with liver disease as a secondary diagnosis. Including all diagnoses captures a burden of GI disease not previously reported.”

In 2018 and 2019, GI diseases and cancers caused 255,407 annual deaths. The most common noncancer deaths were caused by alcohol-associated liver disease (24,110 deaths), hepatic fibrosis/cirrhosis (20,184 deaths), and GI bleeding (9,548 deaths). Among GI-cancer related deaths, colorectal cancer (CRC) caused the most mortalities (52,163 deaths), followed by pancreatic cancer (44,914 deaths), and hepatic/biliary cancer (44,914 deaths). The investigators noted that CRC was disproportionately common among non-Hispanic Black individuals, whereas gastric cancer was relatively high among Hispanic individuals.

“GI cancers account for a large number of diagnoses and deaths annually, with persistent disparities in incidence and mortality rates by race/ethnicity,” the investigators wrote. “Racial, ethnic, and regional disparities in access to most GI endoscopy procedures exist, which suggests an unmet need for GI procedures across the United States.”

A total of 22.2 million endoscopies were performed in 2019, most commonly colonoscopy (13.8 million procedures), followed by upper endoscopy (7.5 million procedures), and flexible sigmoidoscopy (379,883 procedures).

In 2020, the NIH spent $3.1 billion, or approximately 7.5% of its budget, on GI disease research. Digestive diseases captured the bulk of this spending, with $2.3 billion. In the same year, the NIH spent 10.5% of its cancer research budget on GI cancers, with the greatest proportion ($325 million) awarded to CRC research.

“Carefully examining the data in this report can help generate areas for future investigation, prioritize research funding, identify areas of unmet need or disparities, and provide an important overview of the impact of digestive and liver conditions,” the investigators concluded. “We hope that others will use this report as motivation to take a deeper dive into individual diseases. There is much to learn from carefully studying existing data sources.”

The study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. The investigators disclosed no conflicts of interest.

GI, liver, and pancreatic diseases cost the U.S. health care system about $120B per year and account for approximately 250,000 annual deaths, according to a “conservative” estimate from a recent analysis.

These figures emphasize the need for more research funding in the area, along with additional clinical and public health initiatives, reported lead author Anne F. Peery, MD, of the University of North Carolina School of Medicine, Chapel Hill, and colleagues.

“Reports detailing the burden of GI diseases are necessary for clinical research, decision making, and priority setting,” the investigators wrote in Gastroenterology. “Our aim was to describe health care use, expenditures, and research funding across GI, liver, and pancreatic diseases in the United States.”

Dr. Peery and colleagues analyzed data from 14 sources, including the National Institutes of Health; the Centers for Disease Control and Prevention; the National Ambulatory Medical Care Survey; and others. GI-specific outcomes included mortality, readmissions, hospitalizations, office-based visits, and emergency department visits. The investigators also characterized trends in cancers, organ transplants, and GI endoscopy, as well as GI-specific health care costs and NIH research funding. Annual findings were presented for various periods.

Total GI health care spending was $119.6 billion in 2018, down from $135.9 billion in 2015. The top five most costly conditions were biliary tract diseases ($16.9 billion), esophageal disorders ($12.1 billion), abdominal pain ($9.5 billion), abdominal hernias ($9.0 billion), and diverticular disease ($9.0 billion). The investigators noted that medication costs were particularly high for two categories: inflammatory bowel diseases and esophageal disorders, which had prescription drug costs relative to total expenditures of 71% and 53%, respectively.

“This conservative estimate [of $119.6 billion] did not include most GI cancers and likely underestimated the costs associated with some GI conditions,” the investigators noted. “For example, the Medical Expenditure Panel Survey estimate associated with GI bleeding was $300 million. In comparison, the aggregate cost of GI bleeding was more realistically $3.7 billion, as estimated using inpatient data from the National Inpatient Sample.”

In 2016, the most common GI-related diagnosis in the U.S. was abdominal pain (15.7 million annual visits), followed by nausea and vomiting (5.0 million visits), gastroesophageal reflux disorder and reflux esophagitis (4.7 million visits), constipation (3.1 million visits), and abdominal wall/inguinal hernia (2.8 million visits).

The top three most common GI-related hospital admissions in 2018 were GI bleeding (1.3 million admissions), followed by cholelithiasis and cholecystitis (741,060 admissions), then pancreatitis (685,880 admissions). GI bleeding was also the leading cause of 30-day readmission in 2018 (84,533 readmissions).

“We found substantial numbers of GI conditions and symptoms listed in secondary positions on the discharge record,” the investigators wrote. “For example, liver disease accounted for 280,645 discharges with a primary diagnosis; however, there were 13-fold as many discharges (3.6 million in 2018) with liver disease as a secondary diagnosis. Including all diagnoses captures a burden of GI disease not previously reported.”

In 2018 and 2019, GI diseases and cancers caused 255,407 annual deaths. The most common noncancer deaths were caused by alcohol-associated liver disease (24,110 deaths), hepatic fibrosis/cirrhosis (20,184 deaths), and GI bleeding (9,548 deaths). Among GI-cancer related deaths, colorectal cancer (CRC) caused the most mortalities (52,163 deaths), followed by pancreatic cancer (44,914 deaths), and hepatic/biliary cancer (44,914 deaths). The investigators noted that CRC was disproportionately common among non-Hispanic Black individuals, whereas gastric cancer was relatively high among Hispanic individuals.

“GI cancers account for a large number of diagnoses and deaths annually, with persistent disparities in incidence and mortality rates by race/ethnicity,” the investigators wrote. “Racial, ethnic, and regional disparities in access to most GI endoscopy procedures exist, which suggests an unmet need for GI procedures across the United States.”

A total of 22.2 million endoscopies were performed in 2019, most commonly colonoscopy (13.8 million procedures), followed by upper endoscopy (7.5 million procedures), and flexible sigmoidoscopy (379,883 procedures).

In 2020, the NIH spent $3.1 billion, or approximately 7.5% of its budget, on GI disease research. Digestive diseases captured the bulk of this spending, with $2.3 billion. In the same year, the NIH spent 10.5% of its cancer research budget on GI cancers, with the greatest proportion ($325 million) awarded to CRC research.

“Carefully examining the data in this report can help generate areas for future investigation, prioritize research funding, identify areas of unmet need or disparities, and provide an important overview of the impact of digestive and liver conditions,” the investigators concluded. “We hope that others will use this report as motivation to take a deeper dive into individual diseases. There is much to learn from carefully studying existing data sources.”

The study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. The investigators disclosed no conflicts of interest.

GI, liver, and pancreatic diseases cost the U.S. health care system about $120B per year and account for approximately 250,000 annual deaths, according to a “conservative” estimate from a recent analysis.

These figures emphasize the need for more research funding in the area, along with additional clinical and public health initiatives, reported lead author Anne F. Peery, MD, of the University of North Carolina School of Medicine, Chapel Hill, and colleagues.

“Reports detailing the burden of GI diseases are necessary for clinical research, decision making, and priority setting,” the investigators wrote in Gastroenterology. “Our aim was to describe health care use, expenditures, and research funding across GI, liver, and pancreatic diseases in the United States.”

Dr. Peery and colleagues analyzed data from 14 sources, including the National Institutes of Health; the Centers for Disease Control and Prevention; the National Ambulatory Medical Care Survey; and others. GI-specific outcomes included mortality, readmissions, hospitalizations, office-based visits, and emergency department visits. The investigators also characterized trends in cancers, organ transplants, and GI endoscopy, as well as GI-specific health care costs and NIH research funding. Annual findings were presented for various periods.

Total GI health care spending was $119.6 billion in 2018, down from $135.9 billion in 2015. The top five most costly conditions were biliary tract diseases ($16.9 billion), esophageal disorders ($12.1 billion), abdominal pain ($9.5 billion), abdominal hernias ($9.0 billion), and diverticular disease ($9.0 billion). The investigators noted that medication costs were particularly high for two categories: inflammatory bowel diseases and esophageal disorders, which had prescription drug costs relative to total expenditures of 71% and 53%, respectively.

“This conservative estimate [of $119.6 billion] did not include most GI cancers and likely underestimated the costs associated with some GI conditions,” the investigators noted. “For example, the Medical Expenditure Panel Survey estimate associated with GI bleeding was $300 million. In comparison, the aggregate cost of GI bleeding was more realistically $3.7 billion, as estimated using inpatient data from the National Inpatient Sample.”

In 2016, the most common GI-related diagnosis in the U.S. was abdominal pain (15.7 million annual visits), followed by nausea and vomiting (5.0 million visits), gastroesophageal reflux disorder and reflux esophagitis (4.7 million visits), constipation (3.1 million visits), and abdominal wall/inguinal hernia (2.8 million visits).

The top three most common GI-related hospital admissions in 2018 were GI bleeding (1.3 million admissions), followed by cholelithiasis and cholecystitis (741,060 admissions), then pancreatitis (685,880 admissions). GI bleeding was also the leading cause of 30-day readmission in 2018 (84,533 readmissions).

“We found substantial numbers of GI conditions and symptoms listed in secondary positions on the discharge record,” the investigators wrote. “For example, liver disease accounted for 280,645 discharges with a primary diagnosis; however, there were 13-fold as many discharges (3.6 million in 2018) with liver disease as a secondary diagnosis. Including all diagnoses captures a burden of GI disease not previously reported.”

In 2018 and 2019, GI diseases and cancers caused 255,407 annual deaths. The most common noncancer deaths were caused by alcohol-associated liver disease (24,110 deaths), hepatic fibrosis/cirrhosis (20,184 deaths), and GI bleeding (9,548 deaths). Among GI-cancer related deaths, colorectal cancer (CRC) caused the most mortalities (52,163 deaths), followed by pancreatic cancer (44,914 deaths), and hepatic/biliary cancer (44,914 deaths). The investigators noted that CRC was disproportionately common among non-Hispanic Black individuals, whereas gastric cancer was relatively high among Hispanic individuals.

“GI cancers account for a large number of diagnoses and deaths annually, with persistent disparities in incidence and mortality rates by race/ethnicity,” the investigators wrote. “Racial, ethnic, and regional disparities in access to most GI endoscopy procedures exist, which suggests an unmet need for GI procedures across the United States.”

A total of 22.2 million endoscopies were performed in 2019, most commonly colonoscopy (13.8 million procedures), followed by upper endoscopy (7.5 million procedures), and flexible sigmoidoscopy (379,883 procedures).

In 2020, the NIH spent $3.1 billion, or approximately 7.5% of its budget, on GI disease research. Digestive diseases captured the bulk of this spending, with $2.3 billion. In the same year, the NIH spent 10.5% of its cancer research budget on GI cancers, with the greatest proportion ($325 million) awarded to CRC research.

“Carefully examining the data in this report can help generate areas for future investigation, prioritize research funding, identify areas of unmet need or disparities, and provide an important overview of the impact of digestive and liver conditions,” the investigators concluded. “We hope that others will use this report as motivation to take a deeper dive into individual diseases. There is much to learn from carefully studying existing data sources.”

The study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. The investigators disclosed no conflicts of interest.

Click here to read the supplement

Newborn screening for spinal muscular atrophy (SMA) is essential to achieve optimal outcomes for patients with SMA by facilitating early identification and treatment before the onset of irreversible motor neuron loss.

Click here to read the supplement

Newborn screening for spinal muscular atrophy (SMA) is essential to achieve optimal outcomes for patients with SMA by facilitating early identification and treatment before the onset of irreversible motor neuron loss.

Click here to read the supplement

Newborn screening for spinal muscular atrophy (SMA) is essential to achieve optimal outcomes for patients with SMA by facilitating early identification and treatment before the onset of irreversible motor neuron loss.

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

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

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

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

The frequency of showering or bathing and follow-up application of moisturizer appear to be more important factors associated with atopic dermatitis (AD) severity than the duration of showers or baths, results from a prospective observational study found.

Uros Rakita

“Patients may benefit most from counseling on showering or bathing once daily and regularly applying moisturizer after showering or bathing,” one of the study authors, Uros Rakita, MSc, told this news organization. “Recommending less than daily shower frequencies or counseling on specific shower durations may not be necessary.”

During a late-breaking abstract session at the Revolutionizing Atopic Dermatitis symposium, Mr. Rakita, a fourth-year student at Chicago Medical School, North Chicago, presented findings from a prospective, practice-based dermatology study that investigated the longitudinal relationship between different bathing practices and AD severity to help inform patient counseling about optimal bathing practices.

“AD is a chronic, inflammatory skin condition with a diverse set of environmental triggers and exacerbating factors,” Mr. Rakita said during the meeting. “Maintaining adequate skin hydration, skin hygiene, and avoiding triggers are key aspects of AD management across all disease severities. Therefore, understanding optimal shower or bath and moisturizing practices is essential.” In fact, he added, “bathing has been shown to not only hydrate the skin, but also to improve symptoms, remove allergens, and decrease [Staphylococcus] aureus colonization. However, at the same time, concern exists for the potential of inappropriate shower or bathing frequency or durations, as well as inconsistent moisturizer application to worsen disease severity and potentially compromise disease management.”

He noted that current guidelines on bathing frequency and duration among AD patients lack consensus, are limited, and are largely based on studies of pediatric populations.

Mr. Rakita, along with primary study author Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research in the division of dermatology at George Washington University, Washington, and Trisha Kaundinya, a medical student at Northwestern University, Chicago, prospectively evaluated 509 adults with AD who made an average of 2.3 visits at a single dermatology clinic between 2013 and 2020. At each visit, severity of AD signs and symptoms, as well as bathing and moisturizing practices, were assessed.

AD severity was assessed using the objective component of Scoring Atopic Dermatitis (o-SCORAD), intensity of pruritus in the past 3 days (SCORAD-itch), Eczema Area and Severity Index (EASI), Patient-Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). The researchers constructed repeated measures regression models to examine associations of bathing and moisturizing practices with change in AD severity outcome measure scores over time. Multivariable models controlled for age, sex, and race.

In adjusted linear regression models, showering or bathing more than once a day versus once daily was associated with significantly higher scores for SCORAD-itch (0.74; P = .0456), o-SCORAD (4.27; P = .0171), EASI (4.20; P = .0028), POEM (2.61; P = .0021), and DLQI (2.77; P = .0004).

The researchers also found that consistent application of moisturizer after the shower or bath was associated with significantly lower scores for o-SCORAD (–7.22; P < .0001), EASI (–3.91; P = .001) and POEM (–2.68; P = .0002), compared against not applying moisturizer after a shower or bath. However, shower or bath duration of more than, compared against fewer than, 15 minutes was not associated with significantly lower scores for o-SCORAD (1.26; P = .2868), SCORAD-itch (0.17; P = .4987), EASI (0.85; P = .3454), POEM (0.24; P = .6627) or DLQI (–0.40; P = .4318).

“Interestingly, this pattern was present when the reference shower or bath durations were under 10 minutes as well as under 5 minutes,” Mr. Rakita said. “Also, shower or bath frequencies of less than daily, relative to daily frequencies, were not significantly related to longitudinal AD severity.”

Mr. Rakita acknowledged certain limitations of the study, including the fact that the researchers did not examine the potential influence of specific soap and moisturizing products, water hardness, or other bathing features such as water temperature and bath additives.

Lawrence J. Green, MD, who was asked to comment on the study, said that he was not surprised by the finding that moisturizing after bathing improved AD signs and symptoms. “On the other hand, a long-held belief that longer duration of shower/bath time worsens AD was not found to be true,” said Dr. Green, a dermatologist who practices in Rockville, Md., and is also clinical professor of dermatology at George Washington University.

“This provides useful information for practicing dermatologists who wish to provide evidenced-based education about moisturizing and bathing to their AD patients,” he said.

The study was supported by the Agency for Healthcare Research and Quality and the Dermatology Foundation. Dr. Silverberg disclosed that he is a consultant to numerous pharmaceutical companies, receives fees for non-CME/CE services from Eli Lilly, Leo Pharma, Pfizer, Regeneron, and Sanofi Genzyme, as well as contracted research fees from Galderma. Dr. Green disclosed that he is a speaker, consultant, or investigator for numerous pharmaceutical companies. There were no other disclosures.

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

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

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

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

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

Patients ages 65 years and older with atopic dermatitis (AD) have similar disease severity when compared with younger adult patients, but they have more profound sleep disturbances, especially trouble staying asleep.

Those are key findings from a cross-sectional study that Jaya Manjunath, BS, and Jonathan I. Silverberg, MD, PhD, MPH, presented during a poster session at the Revolutionizing Atopic Dermatitis symposium.

“Atopic dermatitis is a chronic, pruritic skin disease associated with sleep disturbance and fatigue affecting adults of all ages,” they wrote. “When caring for geriatric patients, several factors such as sleep disturbance, polypharmacy, cognition, social support, and mobility should be considered. However, little is known about the characteristics of atopic dermatitis in the geriatric population.”

Ms. Manjunath, a student at George Washington University, Washington, and Dr. Silverberg, director of clinical research in the department of dermatology at GWU, recruited patients with AD aged 18 years and older diagnosed by Hanifin-Rajka criteria who were evaluated at an academic medical center between 2014 and 2019. They underwent full body skin exams and completed electronic questionnaires. AD severity was assessed with the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD) total and itch subscores, Investigator’s Global Assessment (IGA), patient-reported Global Assessment of AD severity, and the Patient-Oriented Eczema Measure (POEM).

The researchers also assessed the frequency of sleep disturbances, including difficulty falling asleep and staying asleep, and used multivariable logistic regression models to evaluate associations of age (65 and older vs. 18-64 years) with AD severity, sleep disturbance or fatigue, controlling for total POEM score, sex, and race.

Using adjusted odds ratios, Ms. Manjunath and Dr. Silverberg found that being 65 or older was not associated with AD severity on the EASI (adjusted odds ratio, 1.47); total SCORAD (aOR, 1.10), and itch subscore (aOR, 1.00); IGA (aOR, 1.87); patient-reported Global Assessment of AD severity (aOR, 0.80), or the patient-oriented eczema measure (aOR, 0.55), associations that were not statistically significant.

However, the researchers found that older adult age was associated with an increased number of nights of sleep disturbance from AD in the past week (aOR, 2.14; P = .0142), as well as increased fatigue in the past 7 days (aOR, 1.81; P = .0313), trouble sleeping in the past 7 days (aOR, 1.98; P = .0118), and trouble staying asleep in the past 7 days (aOR, 2.26; P = .0030), but not with difficulty falling asleep in the last 7 days (aOR, 1.16; P = .5996).

“Future studies are needed to determine why geriatric AD patients have increased sleep disturbance and optimal interventions to address their sleep disturbance,” the researchers concluded.

The study was supported by the Agency for Healthcare Research and Quality, the Dermatology Foundation, and by an unrestricted grant from Galderma. Ms. Manjunath disclosed no relevant financial relationships. Dr. Silverberg reported that he is a consultant to and/or an advisory board member for several pharmaceutical companies. He is also a speaker for Regeneron and Sanofi and has received a grant from Galderma.

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

A new study has revealed potential cell-specific effects of the human Janus kinase (JAK) inhibitor tofacitinib, including possible targets – such as intestinal inflammation – for future research and even for increasing the drug’s effects.

The work used both mice and human cell models to explore the drug’s effect in inflammatory bowel disease (IBD). The mouse models suggested that the drug’s pharmacokinetics may be affected by intestinal inflammation. The human cell models seem to identify equilibrative nucleoside transporters as the likely route of cellular uptake of tofacitinib; this mechanism appears to be upregulated during inflammation and could present a therapeutic target to bolster the drug’s effects.

“We identify intestinal inflammation as a decisive modulator of the systemic pharmacokinetics of tofacitinib in mice, which needs to be studied and confirmed in humans. Finally, we decipher an important membrane transport mechanism that regulates cellular uptake of tofacitinib into activated immune cells, suggesting a model that explains a preferred uptake of tofacitinib into activated immune cells and a potential starting point to interfere with and channel such an uptake,” wrote the authors, led by Bernhard Texler and Andreas Zollner, both with the Christian Doppler Laboratory for Mucosal Immunology at the Johannes Kepler University in Linz, Austria, who published the results in Cellular and Molecular Gastroenterology and Hepatology.

IBD-related inflammation likely involves multiple cytokine pathways. The JAK-signal transducers and activator of transcription (JAK-STAT) pathway is downstream to more than 50 cytokines and growth factors, so disruption of their activity by JAK-STAT inhibitors like tofacitinib could counter the effects of more than one cytokine at a time.

Tofacitinib received FDA approval for the treatment of ulcerative colitis in 2018, but the details of its mechanism of action against intestinal inflammation remain poorly understood. For example, despite its efficacy against UC, the drug doesn’t work for Crohn’s disease patients. That may be because the drug affects specific cell populations involved only in UC pathogenesis.

To better understand the drug’s pharmacokinetics, the researchers examined the effects of tofacitinib in cells isolated from human peripheral blood, as well as an experimental mouse model of colitis.

The drug inhibited proliferation of both naïve and memory cytotoxic and helper T cells. At higher concentrations, it had strong effects on innate immune system cells, including monocytes, macrophages, and human intestinal epithelial organoids. It promotes the anti-inflammatory M2 phenotype among monocytes and macrophages. The drug also inhibited the pro-inflammatory M1 phenotype. The researchers observed similar effects in the mouse model of colitis.

The investigators also linked equilibrative nucleoside transporters (ENTs) with uptake of tofacitinib, specifically as a mediating role. These membrane proteins transport nucleosides, nucleobases, and therapeutic analogs like tofacitinib, which mimics the nucleotide adenosine triphosphate (ATP). Targeted inhibitors could potentially influence this process.

The researchers created three-dimensional, in vitro colonic organoids using intestinal epithelial cells from UC patients and healthy human controls. In this model, TNF-alpha can lead to production of pro-inflammatory cytokines, but tofacitinib blocked this effect. That result suggests that intestinal epithelial cells are a previously unidentified tofacitinib target.

Although a large amount of work has been done on the pharmacokinetics of therapeutic antibodies used to treat IBD, the authors point out that little is known about tofacitinib. In a mouse model, the serum concentration of the drug increased after exposure to dextran sulfate sodium (DSS), which triggers an IBD-like condition, and the spike was higher during more intense inflammation. The finding was surprising, considering that therapeutic antibodies typically get eliminated through feces during inflammation. Mice treated with DSS versus control had similar levels of tofacitinib in both urine and the feces, suggesting that inflammation may somehow inhibit the enzymes that metabolize the drug.

The researchers also noted that uptake of tofacitinib into leukocytes increased following stimulation with lipopolysaccharide. Given its structural similarity to ATP, the researchers propose that tofacitinib may enter the cells through adenosine cell membrane transporters ENT1 and ENT2, and some evidence even suggested that the pathway may be strengthened in activated immune cells.

The study received funding from: the Christian Doppler Research Association; the Austrian Federal Ministry of Science, Research, and Economy; and the National Foundation for Research, Technology, and Development. One author is receiving research support from AbbVie and Takeda under the framework of the Christian Doppler Research Society, but the remaining authors have no relevant conflicts of interest.

A new study has revealed potential cell-specific effects of the human Janus kinase (JAK) inhibitor tofacitinib, including possible targets – such as intestinal inflammation – for future research and even for increasing the drug’s effects.

The work used both mice and human cell models to explore the drug’s effect in inflammatory bowel disease (IBD). The mouse models suggested that the drug’s pharmacokinetics may be affected by intestinal inflammation. The human cell models seem to identify equilibrative nucleoside transporters as the likely route of cellular uptake of tofacitinib; this mechanism appears to be upregulated during inflammation and could present a therapeutic target to bolster the drug’s effects.

“We identify intestinal inflammation as a decisive modulator of the systemic pharmacokinetics of tofacitinib in mice, which needs to be studied and confirmed in humans. Finally, we decipher an important membrane transport mechanism that regulates cellular uptake of tofacitinib into activated immune cells, suggesting a model that explains a preferred uptake of tofacitinib into activated immune cells and a potential starting point to interfere with and channel such an uptake,” wrote the authors, led by Bernhard Texler and Andreas Zollner, both with the Christian Doppler Laboratory for Mucosal Immunology at the Johannes Kepler University in Linz, Austria, who published the results in Cellular and Molecular Gastroenterology and Hepatology.

IBD-related inflammation likely involves multiple cytokine pathways. The JAK-signal transducers and activator of transcription (JAK-STAT) pathway is downstream to more than 50 cytokines and growth factors, so disruption of their activity by JAK-STAT inhibitors like tofacitinib could counter the effects of more than one cytokine at a time.

Tofacitinib received FDA approval for the treatment of ulcerative colitis in 2018, but the details of its mechanism of action against intestinal inflammation remain poorly understood. For example, despite its efficacy against UC, the drug doesn’t work for Crohn’s disease patients. That may be because the drug affects specific cell populations involved only in UC pathogenesis.

To better understand the drug’s pharmacokinetics, the researchers examined the effects of tofacitinib in cells isolated from human peripheral blood, as well as an experimental mouse model of colitis.

The drug inhibited proliferation of both naïve and memory cytotoxic and helper T cells. At higher concentrations, it had strong effects on innate immune system cells, including monocytes, macrophages, and human intestinal epithelial organoids. It promotes the anti-inflammatory M2 phenotype among monocytes and macrophages. The drug also inhibited the pro-inflammatory M1 phenotype. The researchers observed similar effects in the mouse model of colitis.

The investigators also linked equilibrative nucleoside transporters (ENTs) with uptake of tofacitinib, specifically as a mediating role. These membrane proteins transport nucleosides, nucleobases, and therapeutic analogs like tofacitinib, which mimics the nucleotide adenosine triphosphate (ATP). Targeted inhibitors could potentially influence this process.

The researchers created three-dimensional, in vitro colonic organoids using intestinal epithelial cells from UC patients and healthy human controls. In this model, TNF-alpha can lead to production of pro-inflammatory cytokines, but tofacitinib blocked this effect. That result suggests that intestinal epithelial cells are a previously unidentified tofacitinib target.

Although a large amount of work has been done on the pharmacokinetics of therapeutic antibodies used to treat IBD, the authors point out that little is known about tofacitinib. In a mouse model, the serum concentration of the drug increased after exposure to dextran sulfate sodium (DSS), which triggers an IBD-like condition, and the spike was higher during more intense inflammation. The finding was surprising, considering that therapeutic antibodies typically get eliminated through feces during inflammation. Mice treated with DSS versus control had similar levels of tofacitinib in both urine and the feces, suggesting that inflammation may somehow inhibit the enzymes that metabolize the drug.

The researchers also noted that uptake of tofacitinib into leukocytes increased following stimulation with lipopolysaccharide. Given its structural similarity to ATP, the researchers propose that tofacitinib may enter the cells through adenosine cell membrane transporters ENT1 and ENT2, and some evidence even suggested that the pathway may be strengthened in activated immune cells.

The study received funding from: the Christian Doppler Research Association; the Austrian Federal Ministry of Science, Research, and Economy; and the National Foundation for Research, Technology, and Development. One author is receiving research support from AbbVie and Takeda under the framework of the Christian Doppler Research Society, but the remaining authors have no relevant conflicts of interest.

A new study has revealed potential cell-specific effects of the human Janus kinase (JAK) inhibitor tofacitinib, including possible targets – such as intestinal inflammation – for future research and even for increasing the drug’s effects.

The work used both mice and human cell models to explore the drug’s effect in inflammatory bowel disease (IBD). The mouse models suggested that the drug’s pharmacokinetics may be affected by intestinal inflammation. The human cell models seem to identify equilibrative nucleoside transporters as the likely route of cellular uptake of tofacitinib; this mechanism appears to be upregulated during inflammation and could present a therapeutic target to bolster the drug’s effects.

“We identify intestinal inflammation as a decisive modulator of the systemic pharmacokinetics of tofacitinib in mice, which needs to be studied and confirmed in humans. Finally, we decipher an important membrane transport mechanism that regulates cellular uptake of tofacitinib into activated immune cells, suggesting a model that explains a preferred uptake of tofacitinib into activated immune cells and a potential starting point to interfere with and channel such an uptake,” wrote the authors, led by Bernhard Texler and Andreas Zollner, both with the Christian Doppler Laboratory for Mucosal Immunology at the Johannes Kepler University in Linz, Austria, who published the results in Cellular and Molecular Gastroenterology and Hepatology.

IBD-related inflammation likely involves multiple cytokine pathways. The JAK-signal transducers and activator of transcription (JAK-STAT) pathway is downstream to more than 50 cytokines and growth factors, so disruption of their activity by JAK-STAT inhibitors like tofacitinib could counter the effects of more than one cytokine at a time.

Tofacitinib received FDA approval for the treatment of ulcerative colitis in 2018, but the details of its mechanism of action against intestinal inflammation remain poorly understood. For example, despite its efficacy against UC, the drug doesn’t work for Crohn’s disease patients. That may be because the drug affects specific cell populations involved only in UC pathogenesis.

To better understand the drug’s pharmacokinetics, the researchers examined the effects of tofacitinib in cells isolated from human peripheral blood, as well as an experimental mouse model of colitis.

The drug inhibited proliferation of both naïve and memory cytotoxic and helper T cells. At higher concentrations, it had strong effects on innate immune system cells, including monocytes, macrophages, and human intestinal epithelial organoids. It promotes the anti-inflammatory M2 phenotype among monocytes and macrophages. The drug also inhibited the pro-inflammatory M1 phenotype. The researchers observed similar effects in the mouse model of colitis.

The investigators also linked equilibrative nucleoside transporters (ENTs) with uptake of tofacitinib, specifically as a mediating role. These membrane proteins transport nucleosides, nucleobases, and therapeutic analogs like tofacitinib, which mimics the nucleotide adenosine triphosphate (ATP). Targeted inhibitors could potentially influence this process.

The researchers created three-dimensional, in vitro colonic organoids using intestinal epithelial cells from UC patients and healthy human controls. In this model, TNF-alpha can lead to production of pro-inflammatory cytokines, but tofacitinib blocked this effect. That result suggests that intestinal epithelial cells are a previously unidentified tofacitinib target.

Although a large amount of work has been done on the pharmacokinetics of therapeutic antibodies used to treat IBD, the authors point out that little is known about tofacitinib. In a mouse model, the serum concentration of the drug increased after exposure to dextran sulfate sodium (DSS), which triggers an IBD-like condition, and the spike was higher during more intense inflammation. The finding was surprising, considering that therapeutic antibodies typically get eliminated through feces during inflammation. Mice treated with DSS versus control had similar levels of tofacitinib in both urine and the feces, suggesting that inflammation may somehow inhibit the enzymes that metabolize the drug.

The researchers also noted that uptake of tofacitinib into leukocytes increased following stimulation with lipopolysaccharide. Given its structural similarity to ATP, the researchers propose that tofacitinib may enter the cells through adenosine cell membrane transporters ENT1 and ENT2, and some evidence even suggested that the pathway may be strengthened in activated immune cells.

The study received funding from: the Christian Doppler Research Association; the Austrian Federal Ministry of Science, Research, and Economy; and the National Foundation for Research, Technology, and Development. One author is receiving research support from AbbVie and Takeda under the framework of the Christian Doppler Research Society, but the remaining authors have no relevant conflicts of interest.

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

The pandemic has created a hostile environment for pregnant people and their babies.

Stress levels among expectant mothers have soared. Pregnant women with COVID are 5 times as likely as uninfected pregnant people to require intensive care and 22 times as likely to die. Infected moms are four times as likely to have a stillborn child.

Yet some of the pandemic’s greatest threats to infants’ health may not be apparent for years or even decades.

That’s because babies of COVID-infected moms are 60% more likely to be born very prematurely, which increases the danger of infant mortality and long-term disabilities such as cerebral palsy, asthma, and hearing loss, as well as a child’s risk of adult disease, including depression, anxiety, heart disease, and kidney disease.

Studies have linked fever and infection during pregnancy to developmental and psychiatric conditions such as autism, depression, and schizophrenia.

“Some of these conditions do not show up until middle childhood or early adult life, but they have their origins in fetal life,” said Evdokia Anagnostou, MD, a child neurologist at Holland Bloorview Kids Rehabilitation Hospital and a pediatrics professor at the University of Toronto.

For fetuses exposed to COVID, the greatest danger is usually not the coronavirus itself, but the mother’s immune system.

Both severe COVID infections and the strain of the pandemic can expose fetuses to harmful inflammation, which can occur when a mother’s immune system is fighting a virus or when stress hormones send nonstop alarm signals.

Prenatal inflammation “changes the way the brain develops and, depending on the timing of the infection, it can change the way the heart or kidneys develop,” Dr. Anagnostou said.

Although health officials have strongly recommended COVID vaccines for pregnant people, only 35% are fully vaccinated.

At least 150,000 pregnant women have been diagnosed with COVID; more than 25,000 of them have been hospitalized, and 249 have died, according to the Centers for Disease Control and Prevention.

Although most babies will be fine, even a small increase in the percentage of children with special medical or educational needs could have a large effect on the population, given the huge number of COVID infections, Dr. Anagnostou said.

“If someone has a baby who is doing well, that is what they should focus on,” Dr. Anagnostou said. “But from a public health point of view, we need to follow women who experienced severe COVID and their babies to understand the impact.”

Learning from history

Researchers in the United States and other countries are already studying “the COVID generation” to see whether these children have more health issues than those conceived or born before 2020.

Previous crises have shown that the challenges fetuses face in the womb – such as maternal infections, hunger, stress, and hormone-disrupting chemicals – can leave a lasting imprint on their health, as well as that of their children and grandchildren, said Frederick Kaskel, MD, director of pediatric nephrology at the Children’s Hospital at Montefiore, New York.

People whose mothers were pregnant during surges in the 1918 influenza pandemic, for example, had poorer health throughout their lives, compared with Americans born at other times, said John McCarthy, who is a medical student at Albert Einstein College of Medicine, New York, and cowrote a recent review in JAMA Pediatrics with Dr. Kaskel.

Researchers don’t know exactly which moms were infected with pandemic flu, Mr. McCarthy said. But women who were pregnant during major surges – when infection was widespread – had children with higher rates of heart disease or diabetes. These children were also less successful in school, less economically productive, and more likely to live with a disability.

Because organ systems develop during different periods of pregnancy, fetuses exposed during the first trimester may face different risks than those exposed toward the end of pregnancy, Mr. McCarthy said. For example, people born in the fall of 1918 were 50% more likely than others to develop kidney disease; that may reflect an exposure to the pandemic in the third trimester, while the kidneys were still developing.

Nearly 2 years into the COVID pandemic, researchers have begun to publish preliminary observations of infants exposed to COVID infections and stress before birth.

Although Dr. Anagnostou noted that it’s too early to reach definitive conclusions, “there is evidence that babies born to moms with severe COVID infections have changes to their immune system,” she said. “It’s enough to make us worry a little bit.”

Damaging a fetal security system

The good news about the coronavirus is that it seldom crosses the placenta, the organ tasked with protecting a developing fetus from infections and providing it with oxygen. So moms with COVID rarely give the virus to their children before birth.

That’s important, because some viruses that directly infect the fetus – such as Zika – can cause devastating birth defects, said Karin Nielsen-Saines, MD, a specialist in pediatric infectious diseases at University of California, Los Angeles.

But studies also suggest that inflammation from a mother’s COVID infection can injure the placenta, said Jeffery Goldstein, MD, an assistant professor of pathology at Northwestern University, Chicago. In a study published in American Journal of Clinical Pathology , Dr. Goldstein and his coauthors found that placentas from COVID-infected moms had more abnormal blood vessels than placentas from patients without COVID, making it harder for them to deliver sufficient oxygen to the fetus.

Placental damage can also lead to preeclampsia, a serious complication of pregnancy that can cause a mother’s blood pressure to spike.

Preeclampsia occurs when blood vessels in the placenta don’t develop or function properly, forcing the mother’s heart to work harder to get blood to the fetus, which may not receive enough oxygen and nutrients. Preeclampsia also predisposes women to heart attacks and strokes later in life.

Rewiring the immune system

In some cases, COVID also appears to rewire a baby’s immune response, Dr. Nielsen-Saines said.

In an October study in the journal Cell Reports Medicine, Dr. Nielsen-Saines and her coauthors found that infants born to people with severe COVID infections had a different mix of immune cells and proteins than other babies. None of the newborns tested positive for the coronavirus.

The immune changes are concerning, Dr. Nielsen-Saines said, because this pattern of immune cells and proteins has previously been found in infants with respiratory problems and in some cases poor neurodevelopment.

Notably, all the babies in her study appear healthy, said Dr. Nielsen-Saines, who plans to follow them for 3 years to see whether these early signals translate into developmental delays, such as problems talking, walking, or interacting with others.

“How big of a difference does any of this make in the baby?” asked Dr. Anagnostou. “We won’t know for a few years. All we can do is try to be as prepared as possible.”

Increasing the risk for boys

Boys could face higher risks from COVID, even before birth.

Males are generally more vulnerable than females as fetuses and newborns; they’re more likely to be born prematurely and to die as infants. Preterm boys also have a higher risk of disability and death.

But coronavirus infection poses special dangers, said Sabra Klein, PhD, a professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health, Baltimore.

That’s because boys are disproportionately affected by conditions linked to maternal infections. Boys are four times as likely as girls to be diagnosed with autism or attention-deficit/hyperactivity disorder, for example, while men are 75% more likely than women to develop schizophrenia.

Scientists don’t fully understand why boys appear more fragile in the womb, although testosterone – which can dampen immune response – may play a role, said Kristina Adams Waldorf, MD, a professor of obstetrics and gynecology at the University of Washington.

Men generally mount weaker immune responses than women and more often develop severe COVID infections. Recent research suggests boys with COVID are more likely than girls to become seriously ill or develop a rare inflammatory condition called multisystem inflammatory syndrome.

New research on COVID could help illuminate this vulnerability.

In a study published in October, researchers found that the sex of a fetus influences the way its placenta responds to COVID, as well as how its mother’s immune system responds.

Pregnant people infected with COVID made fewer antibodies against the coronavirus if they were carrying male fetuses than if they were carrying females. Mothers also transferred fewer antibodies to boys than to girls, said Andrea Edlow, MD, senior author of the study and a maternal-fetal medicine specialist at Massachusetts General Hospital, Boston.

When examining the placentas of male fetuses after delivery, researchers found changes that could leave boys less protected against damaging inflammation.

The sex of a fetus can influence its mother’s response to other illnesses, as well.

For example, research shows that pregnant women with asthma have worse symptoms if they’re carrying a female. Women carrying males are slightly more likely to develop gestational diabetes.

Dr. Edlow said her findings raise questions about the “cross talk” between mother and baby. “The mom’s immune system is sensing there is a male fetus,” Dr. Edlow said. “And the fetus is actively communicating with the mom’s immune system.”

Boosting toxic stress

Rates of depression and stress among pregnant women have increased dramatically during the pandemic.

That’s concerning because chronic stress can lead to inflammation, affecting the babies of both infected and uninfected women, Dr. Anagnostou said.

Studies consistently show that infants born to mothers who experience significant stress during pregnancy have higher rates of short- and long-term health damage – including heart defects and obesity – than babies born to women with less stress.

“We know that inflammation directly influences the way a baby’s brain develops,” said Elinor Sullivan, PhD, an associate professor in psychiatry at Oregon Health & Science University, Portland.

Lockdowns, travel restrictions and physical distancing left many pregnant women without the support of family and friends. The stress of losing a loved one, a job, or a home further heightens the risks to moms and babies, said Dr. Sullivan, who is following children born during the pandemic for 5 years.

In research that has not yet been published, Dr. Sullivan found that babies of women who were pregnant during the pandemic showed more sadness and negative emotions in the first year of life, compared with infants of women who were pregnant before the pandemic.

The findings show the importance of helping and protecting pregnant people before and after delivery, said Dr. Sullivan, who conducted a separate study that found women who received more social support were less depressed.

Italian researchers are also studying the effect of maternal stress on infants’ behavior, as well as the way their genes are regulated.

Although stress-related inflammation doesn’t alter the structure of a baby’s genes, it can influence whether they’re turned on and off, said Livio Provenzi, PhD, a psychologist at the C. Mondino National Institute of Neurology Foundation in Pavia, Italy.

In Dr. Provenzi’s study of 163 mother-baby pairs he found differences in how genes that regulate the stress response were activated. Genes that help people respond to stress were more likely to be turned off in babies whose moms reported the most stress during pregnancy. The same moms also reported that their babies cried more and were fussier when they were 3 months old.

Researchers usually prefer to make in-person observations of babies as they interact with their mothers, Dr. Provenzi said. But because of the pandemic, Dr. Provenzi asked mothers to fill out questionnaires about infant behavior. He plans to observe mothers and babies in person when the children are 12 months old.

While vaccinating pregnant people is the best way to protect them and their fetuses from the virus, Dr. Anagnostou said, society needs to do more to preserve expectant mothers’ mental health.

“We can’t escape the fact that we’ve lived through 2 years of a pandemic,” Dr. Anagnostou said. “But we can think about opportunities for reducing the risk.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.