INDIANAPOLIS – Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”

Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

INDIANAPOLIS – Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”

Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

INDIANAPOLIS – Treating atopic dermatitis (AD) in children and adolescents with skin of color requires an acumen that extends well beyond the skin, said Candrice R. Heath, MD, at the annual meeting of the Society for Pediatric Dermatology.

This involves the practice of cultural humility, which Dr. Heath defined as a commitment to learn about all aspects of patients to truly understand them, including their race, access to health care, and socioeconomic status.

“We can continue to prioritize learning about all different types of skin tones and hair types, but we really have to commit to advocating for what our patients deserve in every way,” Dr. Heath, director of pediatric dermatology at Temple University, Philadelphia, said during her presentation at the meeting.

“That means advocating for kids to have access to better housing and for increasing health literacy programs in our hospitals, so that all our patients can understand what’s happening and how to navigate the health system,” she said. “It also means increasing diversity in our clinical trials by taking a few extra moments with the patient and family of color who might be eligible to participate in a clinical trial. We have work to do.”

To illustrate her points, she discussed the case of a 6-year-old Black patient, whose parents bring him into the clinic complaining about dark marks on the skin. The areas are itchy and the doctor figures, “this is a slam dunk; this is AD,” Dr. Heath said. “You talk about the diagnosis, and you give your treatment plan.

“But the issue is, in the parking lot when the patient’s family leaves, they feel like you didn’t help them at all,” she continued. “You didn’t understand what they came in for. They didn’t receive a treatment for what they came in for, because the initial complaint was dark marks on the skin, which is postinflammatory hyperpigmentation. We know that patients are distressed by this.”

As evidence, she cited a cross-sectional study that assessed the impact of hyperpigmentation and hyperchromia on quality of life in adults, published in the Journal of the American Academy of Dermatology. People who reported the highest levels of distress were women, those with postinflammatory hyperpigmentation, those with fewer formal years of education, and those who had higher out-of-pocket spending on skin-enhancing products.

“So, when you see hyperpigmentation in your AD patients of color, acknowledge it; say, ‘I see this pigmentation change,’ ” Dr. Heath advised. “Talk about how controlling the AD with a topical steroid or other treatment option can have a positive impact on that.”

However, she added that sometimes patients have steroid phobia, possibly because they believe the topical steroids are causing the pigmentation changes, “especially in cases of hypopigmentation, so I take the time to reassure patients so that they will not be fearful about using the medication.”

Parents of patients with skin of color who have AD may harbor other “invisible” concerns during office visits, she continued, including prior experiences with dermatologists that may not have been positive, difficulty accessing pediatric dermatologists, or a general mistrust of the health care system.

“All of that is going on in the room with your patients, particularly those with skin of color and those who feel marginalized,” said Dr. Heath, who is also a faculty scholar at Temple University medical school’s office of health equity, diversity and inclusion. “Of course, we can’t fix everything. But we can commit to approaching our visits with cultural humility.”

For patients with skin of color, she pointed out, other upstream effects impact AD care and outcomes, including well-documented socioeconomic factors.

“One of the equalizing factors is that we as pediatric dermatologists can think about increasing our education regarding skin of color,” Dr. Heath said.

For example, an analysis of data from the 2002 to 2012 National Inpatient Sample found that the main risk factors for inpatient hospitalization for AD were being non-White, having lowest-quartile household income, and having Medicaid or no insurance, researchers reported in 2018.

A separate multicenter study of 1,437 mother-child pairs with known AD found that non-Hispanic Black children and Hispanic children had greater odds of persistent AD than non-Hispanic White children, according to a 2019 study. Another large prospective cohort study published in 2019 found that AD prevalence and persistence is highest in U.S. urban children who are female or Black, and urban children with AD are more likely to have poor quality of life and asthma.

A few months after that study was published, researchers reported results from an analysis of data from the 2007-2008 National Survey of Children’s Health, which found that children who perceive the neighborhood they lived in as unsafe, unsupportive, or underdeveloped had a higher prevalence of AD and a higher severity of AD. The same year, a study of the social and economic risk factors for moderate to severe AD found that Black children were more likely to come from homes with a lower household income, lower parental education attainment, lack of home ownership, and live between two residences, and have exposure to smoke.

“Disease recognition is one thing, but we also want everyone to be aware of these other factors,” she said, “because some patients do need a little bit more care and help to be able to access the medications that they need and gain access to us.”

 

Follicular, nummular eczema

In her clinical experience, the most common clinical variants of AD in patients with skin of color is follicular eczema. “Examine the patient, apply your hand to the affected area, and you can feel the papules beneath your fingertips,” she advised.

“That’s what I teach my residents and medical students,” she said. “If you are looking for erythema to seal your diagnosis of AD, it may not happen. You may see more of a violaceous hue and sometimes you may not find it at all, depending on the patient’s skin tone. If I find an area of normal appearing skin and then look back at the area of active skin disease, I go back and forth until I’m able to train my eye to be able to see those violaceous and erythematous hues more easily.”

Nummular eczema can also be a challenge in AD patients with skin of color.

“I like to listen to buzz words,” Dr. Heath said. “If a parent says, ‘my child has been diagnosed with ringworm multiple times,’ I zoom in on that. We know that kids can get tinea corporis, but usually not multiple times. I ask about all the things that can be associated with AD, and often we do see these nummular plaques on the skin and do some education about that. I also talk to their pediatrician or send information to that person so that they can be aware that nummular eczema is a form of AD.”

She noted that AD of the scalp may be confused with tinea capitis, especially in young Black children with moderate to severe AD. In her experience, triamcinolone 0.1% ointment works well for AD of the scalp.

She concluded her presentation by noting that there is no easy solution to treating AD in young patients with skin of color. “It’s way more than just eczema. We can help people see AD in a different way. My goal is to see the value in challenging ourselves to understand the impact of what happens outside of the exam room on these patients.”

Dr. Heath disclosed that she has served as a consultant for several pharmaceutical companies, including Regeneron, Janssen, Arcutis, Johnson and Johnson, Cassiopea, and Lilly.

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

Loss of smell, not disease severity, predicts persistent cognitive impairment 1 year after SARS-CoV-2 infection, preliminary results of new research suggest.

The findings provide important insight into the long-term cognitive impact of COVID-19, said study investigator Gabriela Gonzalez-Alemán, PhD, professor at Pontifical Catholic University of Argentina, Buenos Aires.

The more information that can be gathered on factors increasing risks for this cognitive impact, “the better we can track it and begin to develop methods to prevent it,” she said.

The findings were presented at the Alzheimer’s Association International Conference.
 

Memory, attention problems

COVID-19 has infected more than 570 million people worldwide. Related infections may result in long-term sequelae, including neuropsychiatric symptoms, said Dr. Gonzalez-Alemán.

In older adults, COVID-19 sequelae may resemble early Alzheimer’s disease, and the two conditions may share risk factors and blood biomarkers.

The new study highlighted 1-year results from a large, prospective cohort study from Argentina. Researchers used measures to evaluate long-term consequences of COVID-19 in older adults recommended by the Alzheimer’s Association Consortium on Chronic Neuropsychiatric Sequelae of SARS-CoV-2 infection (CNS SC2).

Harmonizing definitions and methodologies for studying COVID-19’s impact on the brain allows consortium members to compare study results, said Dr. Gonzalez-Alemán.

The investigators used the health registry in the province of Jujuy, situated in the extreme northwestern part of Argentina. The registry includes all SARS-CoV-2 testing data for the entire region.

The investigators randomly invited adults aged 60 years and older from the registry to participate in the study. The current analysis included 766 adults aged 55-95 years (mean age 66.9 years; 57% female) with an average of 10.4 years of education. The education system in Argentina includes 12 years of school before university.

Investigators stratified subjects by polymerase chain reaction testing status. Of the total, 88.4% were infected with COVID and 11.6% were controls (subjects without COVID).

The neurocognitive assessment of participants included four cognitive domains: memory, attention, language, and executive function, and an olfactory test that determined degree of olfactory dysfunction. Cognitive impairment was defined as z scores below –2.

Researchers divided participants into groups according to cognitive performance. These included normal cognition, memory-only impairment (single domain; 11.7%), impairment in attention and executive function without memory impairment (two domains; 8.3%), and multiple domain impairment (11.6%).

“Our participants showed a predominance of memory impairment as would be seen in Alzheimer’s disease,” noted Dr. Gonzalez-Alemán. “And a large group showed a combination of memory and attention problems.”

About 40% of the study sample – but no controls – had olfactory dysfunction.

“All the subjects that had a severe cognitive impairment also had anosmia [loss of smell],” said Dr. Gonzalez-Alemán. “We established an association between olfactory dysfunction and cognitive performance and impairment.”

The analysis showed that severity of anosmia, but not clinical status, significantly predicted cognitive impairment. “So, anosmia could be a good predictor of cognitive impairment after COVID-19 infection,” said Dr. Gonzalez-Alemán.

For individuals older than 60 years, cognitive impairment can be persistent, as can be olfactory dysfunction, she added.

Results of a 1-year phone survey showed about 71.8% of subjects had received three vaccine doses and 24.9% two doses. About 12.5% of those with three doses were reinfected and 23.3% of those with two doses were reinfected.
 

Longest follow-up to date

Commenting on the research, Heather Snyder, PhD, vice president, medical and scientific relations at the Alzheimer’s Association, noted the study is “the longest follow-up we’ve seen” looking at the connection between persistent loss of smell and cognitive changes after a COVID-19 infection.

The study included a “fairly large” sample size and was “unique” in that it was set up in a part of the country with centralized testing, said Dr. Snyder.

The Argentinian group is among the most advanced of those connected to the CNS SC2, said Dr. Snyder.

Members of this Alzheimer’s Association consortium, said Dr. Snyder, regularly share updates of ongoing studies, which are at different stages and looking at various neuropsychiatric impacts of COVID-19. It is important to bring these groups together to determine what those impacts are “because no one group will be able to do this on their own,” she said. “We saw pretty early on that some individuals had changes in the brain, or changes in cognition, and loss of sense of smell or taste, which indicates there’s a connection to the brain.”

However, she added, “there’s still a lot we don’t know” about this connection.

The study was funded by Alzheimer’s Association and FULTRA.

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

Rapid deterioration in sense of smell is a strong predictor of both Alzheimer’s-related cognitive impairment and loss of volume in specific brain regions linked to both Alzheimer’s disease and smell, according to new research findings.

Olfactory dysfunction is common in late life and well documented among people with Alzheimer’s disease. However, it was unknown whether faster olfactory decline predicts either onset of Alzheimer’s disease or structural brain changes associated with Alzheimer’s disease.

In a study published online in Alzheimer’s and Dementia, Jayant M. Pinto, MD, and his colleagues at the University of Chicago Medical Center reported that among older adults with normal cognition at baseline, people who experienced rapid loss of sense of smell were more likely to be subsequently diagnosed with mild cognitive impairment (MCI) or dementia, compared with those who did not.

Participants were recruited from Rush University’s Memory and Aging Project, a longitudinal cohort of older adults who undergo yearly cognitive and sensory exams, including a scratch test of 12 common smells to identify. The Rush study “was ahead of the curve in looking at smell,” Dr. Pinto said in an interview. “It gave us a very valuable resource with which to attack these questions.”

Dr. Pinto has long investigated links between smell and accelerated aging; in 2014 his group published the finding that olfactory dysfunction could predict death within 5 years in older adults, and in 2018 they reported that olfactory dysfunction could predict dementia.
 

Smell and cognition over time

For the current study, Dr. Pinto said, “we were able to look at the question not just using a single point in time, but a more granular trajectory of smell loss. Measuring change year by year showed that the faster people’s sense of smell declined, the more likely they were to be diagnosed with MCI or Alzheimer’s disease.”

Dr. Pinto and his colleagues evaluated results from 515 adults (mean age 76.6, 78% female, 94% White) with no cognitive impairment and at least 3 years of normal results on smell tests at baseline. The subjects were followed for a mean 8 years. One hundred subjects (19%) were diagnosed with MCI or dementia by the end of the study period. A subset of the cohort (n = 121) underwent structural magnetic resonance imaging (MRI) between their final smell tests and the study’s end. Of these, most still had normal cognition; 17 individuals had MCI.

Patients’ individual trajectories of smell loss were mapped as slopes. After adjusting for expected differences in age and sex, the investigators found steeper decline associated with greater risk of incident MCI or dementia (odds ratio, 1.89; 95% confidence interval, 1.26-2.90; P < .01). The risk was comparable to that of carrying an apo E ε4 allele, the key risk variant for late-onset Alzheimer’s disease, but was independent of apo E status. The association was strongest among subjects younger than 76 years.
 

Olfactory decline and brain volume

Dr. Pinto and his colleagues, including lead author Rachel R. Pacyna, a 4th-year medical student at the University of Chicago, also sought to identify brain volume changes corresponding with olfactory decline and Alzheimer’s disease. The researchers hypothesized that certain brain regions not seen affected in Alzheimer’s disease would remain unchanged regardless of olfactory status, but that regions associated with smell and Alzheimer’s disease would see smaller volumes linked with olfactory decline.

Faster olfactory decline did predict lower gray matter volume in olfactory regions, even after controlling for apo E status and other known risk factors. Conversely, cognitively unimpaired patients undergoing MRI saw more gray matter volume in primary olfactory and temporal brain regions, compared with those with cognitive symptoms.

Taken together, the findings suggest that “change in sense of smell is better than looking at sense of smell at one time point,” Dr. Pinto commented. “There are other reasons people have impaired sense of smell: car accidents, COVID, other viruses and infections. But if you identify on a time course those who are starting to lose it faster, these are the people on whom we need to focus.”
 

Not yet diagnostic

More work needs to be done to establish thresholds for smell loss that could be useful in clinical or investigative settings as a marker of dementia risk, Dr. Pinto acknowledged. “Everyone gets their hearing tested; everyone gets their vision tested. It’s not as easy to get your sense of smell tested. But this study is telling people that if we were to start measuring it routinely, we could actually use it.”

Smell testing “could become a component of a diagnostic battery that includes things like genotyping and cerebrospinal fluid markers, but adds a little more information. It could be useful in clinical prevention trials to identify people at the highest risk, as smell loss presents quite a few years before MCI or Alzheimer’s disease.”

The investigators acknowledged that their findings need to be replicated in more diverse cohorts that better represent the Alzheimer’s population in the United States. Another limitation of their study, they said, was that the method used to calculate the rate of olfactory decline “was based on slope of measured time points assuming linearity, which may oversimplify the complexity of olfactory changes in normal aging and during the preclinical Alzheimer’s disease period.” The study was funded by the National Institutes of Health. Dr. Pinto disclosed receiving consulting fees from Sanofi/Regeneron, Optinose, and Genentech not related to this work.

Rapid deterioration in sense of smell is a strong predictor of both Alzheimer’s-related cognitive impairment and loss of volume in specific brain regions linked to both Alzheimer’s disease and smell, according to new research findings.

Olfactory dysfunction is common in late life and well documented among people with Alzheimer’s disease. However, it was unknown whether faster olfactory decline predicts either onset of Alzheimer’s disease or structural brain changes associated with Alzheimer’s disease.

In a study published online in Alzheimer’s and Dementia, Jayant M. Pinto, MD, and his colleagues at the University of Chicago Medical Center reported that among older adults with normal cognition at baseline, people who experienced rapid loss of sense of smell were more likely to be subsequently diagnosed with mild cognitive impairment (MCI) or dementia, compared with those who did not.

Participants were recruited from Rush University’s Memory and Aging Project, a longitudinal cohort of older adults who undergo yearly cognitive and sensory exams, including a scratch test of 12 common smells to identify. The Rush study “was ahead of the curve in looking at smell,” Dr. Pinto said in an interview. “It gave us a very valuable resource with which to attack these questions.”

Dr. Pinto has long investigated links between smell and accelerated aging; in 2014 his group published the finding that olfactory dysfunction could predict death within 5 years in older adults, and in 2018 they reported that olfactory dysfunction could predict dementia.
 

Smell and cognition over time

For the current study, Dr. Pinto said, “we were able to look at the question not just using a single point in time, but a more granular trajectory of smell loss. Measuring change year by year showed that the faster people’s sense of smell declined, the more likely they were to be diagnosed with MCI or Alzheimer’s disease.”

Dr. Pinto and his colleagues evaluated results from 515 adults (mean age 76.6, 78% female, 94% White) with no cognitive impairment and at least 3 years of normal results on smell tests at baseline. The subjects were followed for a mean 8 years. One hundred subjects (19%) were diagnosed with MCI or dementia by the end of the study period. A subset of the cohort (n = 121) underwent structural magnetic resonance imaging (MRI) between their final smell tests and the study’s end. Of these, most still had normal cognition; 17 individuals had MCI.

Patients’ individual trajectories of smell loss were mapped as slopes. After adjusting for expected differences in age and sex, the investigators found steeper decline associated with greater risk of incident MCI or dementia (odds ratio, 1.89; 95% confidence interval, 1.26-2.90; P < .01). The risk was comparable to that of carrying an apo E ε4 allele, the key risk variant for late-onset Alzheimer’s disease, but was independent of apo E status. The association was strongest among subjects younger than 76 years.
 

Olfactory decline and brain volume

Dr. Pinto and his colleagues, including lead author Rachel R. Pacyna, a 4th-year medical student at the University of Chicago, also sought to identify brain volume changes corresponding with olfactory decline and Alzheimer’s disease. The researchers hypothesized that certain brain regions not seen affected in Alzheimer’s disease would remain unchanged regardless of olfactory status, but that regions associated with smell and Alzheimer’s disease would see smaller volumes linked with olfactory decline.

Faster olfactory decline did predict lower gray matter volume in olfactory regions, even after controlling for apo E status and other known risk factors. Conversely, cognitively unimpaired patients undergoing MRI saw more gray matter volume in primary olfactory and temporal brain regions, compared with those with cognitive symptoms.

Taken together, the findings suggest that “change in sense of smell is better than looking at sense of smell at one time point,” Dr. Pinto commented. “There are other reasons people have impaired sense of smell: car accidents, COVID, other viruses and infections. But if you identify on a time course those who are starting to lose it faster, these are the people on whom we need to focus.”
 

Not yet diagnostic

More work needs to be done to establish thresholds for smell loss that could be useful in clinical or investigative settings as a marker of dementia risk, Dr. Pinto acknowledged. “Everyone gets their hearing tested; everyone gets their vision tested. It’s not as easy to get your sense of smell tested. But this study is telling people that if we were to start measuring it routinely, we could actually use it.”

Smell testing “could become a component of a diagnostic battery that includes things like genotyping and cerebrospinal fluid markers, but adds a little more information. It could be useful in clinical prevention trials to identify people at the highest risk, as smell loss presents quite a few years before MCI or Alzheimer’s disease.”

The investigators acknowledged that their findings need to be replicated in more diverse cohorts that better represent the Alzheimer’s population in the United States. Another limitation of their study, they said, was that the method used to calculate the rate of olfactory decline “was based on slope of measured time points assuming linearity, which may oversimplify the complexity of olfactory changes in normal aging and during the preclinical Alzheimer’s disease period.” The study was funded by the National Institutes of Health. Dr. Pinto disclosed receiving consulting fees from Sanofi/Regeneron, Optinose, and Genentech not related to this work.

Rapid deterioration in sense of smell is a strong predictor of both Alzheimer’s-related cognitive impairment and loss of volume in specific brain regions linked to both Alzheimer’s disease and smell, according to new research findings.

Olfactory dysfunction is common in late life and well documented among people with Alzheimer’s disease. However, it was unknown whether faster olfactory decline predicts either onset of Alzheimer’s disease or structural brain changes associated with Alzheimer’s disease.

In a study published online in Alzheimer’s and Dementia, Jayant M. Pinto, MD, and his colleagues at the University of Chicago Medical Center reported that among older adults with normal cognition at baseline, people who experienced rapid loss of sense of smell were more likely to be subsequently diagnosed with mild cognitive impairment (MCI) or dementia, compared with those who did not.

Participants were recruited from Rush University’s Memory and Aging Project, a longitudinal cohort of older adults who undergo yearly cognitive and sensory exams, including a scratch test of 12 common smells to identify. The Rush study “was ahead of the curve in looking at smell,” Dr. Pinto said in an interview. “It gave us a very valuable resource with which to attack these questions.”

Dr. Pinto has long investigated links between smell and accelerated aging; in 2014 his group published the finding that olfactory dysfunction could predict death within 5 years in older adults, and in 2018 they reported that olfactory dysfunction could predict dementia.
 

Smell and cognition over time

For the current study, Dr. Pinto said, “we were able to look at the question not just using a single point in time, but a more granular trajectory of smell loss. Measuring change year by year showed that the faster people’s sense of smell declined, the more likely they were to be diagnosed with MCI or Alzheimer’s disease.”

Dr. Pinto and his colleagues evaluated results from 515 adults (mean age 76.6, 78% female, 94% White) with no cognitive impairment and at least 3 years of normal results on smell tests at baseline. The subjects were followed for a mean 8 years. One hundred subjects (19%) were diagnosed with MCI or dementia by the end of the study period. A subset of the cohort (n = 121) underwent structural magnetic resonance imaging (MRI) between their final smell tests and the study’s end. Of these, most still had normal cognition; 17 individuals had MCI.

Patients’ individual trajectories of smell loss were mapped as slopes. After adjusting for expected differences in age and sex, the investigators found steeper decline associated with greater risk of incident MCI or dementia (odds ratio, 1.89; 95% confidence interval, 1.26-2.90; P < .01). The risk was comparable to that of carrying an apo E ε4 allele, the key risk variant for late-onset Alzheimer’s disease, but was independent of apo E status. The association was strongest among subjects younger than 76 years.
 

Olfactory decline and brain volume

Dr. Pinto and his colleagues, including lead author Rachel R. Pacyna, a 4th-year medical student at the University of Chicago, also sought to identify brain volume changes corresponding with olfactory decline and Alzheimer’s disease. The researchers hypothesized that certain brain regions not seen affected in Alzheimer’s disease would remain unchanged regardless of olfactory status, but that regions associated with smell and Alzheimer’s disease would see smaller volumes linked with olfactory decline.

Faster olfactory decline did predict lower gray matter volume in olfactory regions, even after controlling for apo E status and other known risk factors. Conversely, cognitively unimpaired patients undergoing MRI saw more gray matter volume in primary olfactory and temporal brain regions, compared with those with cognitive symptoms.

Taken together, the findings suggest that “change in sense of smell is better than looking at sense of smell at one time point,” Dr. Pinto commented. “There are other reasons people have impaired sense of smell: car accidents, COVID, other viruses and infections. But if you identify on a time course those who are starting to lose it faster, these are the people on whom we need to focus.”
 

Not yet diagnostic

More work needs to be done to establish thresholds for smell loss that could be useful in clinical or investigative settings as a marker of dementia risk, Dr. Pinto acknowledged. “Everyone gets their hearing tested; everyone gets their vision tested. It’s not as easy to get your sense of smell tested. But this study is telling people that if we were to start measuring it routinely, we could actually use it.”

Smell testing “could become a component of a diagnostic battery that includes things like genotyping and cerebrospinal fluid markers, but adds a little more information. It could be useful in clinical prevention trials to identify people at the highest risk, as smell loss presents quite a few years before MCI or Alzheimer’s disease.”

The investigators acknowledged that their findings need to be replicated in more diverse cohorts that better represent the Alzheimer’s population in the United States. Another limitation of their study, they said, was that the method used to calculate the rate of olfactory decline “was based on slope of measured time points assuming linearity, which may oversimplify the complexity of olfactory changes in normal aging and during the preclinical Alzheimer’s disease period.” The study was funded by the National Institutes of Health. Dr. Pinto disclosed receiving consulting fees from Sanofi/Regeneron, Optinose, and Genentech not related to this work.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.

About one in four patients with non–small cell lung cancer (NSCLC) have an unsatisfactory antibody response to the Omicron variant following COVID-19 vaccination, according to a new study.

The study was published in the Journal of Clinical Oncology.

“Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant,” wrote the authors, who were led by Rafi Ahmed, PhD, Emory University, Atlanta.

Researchers found that 18% had no detectable antibody at all and active treatment type had no association with vaccine response.

Researchers examined antibody titers among 82 NSCLC patients and 53 healthy volunteers. They collected blood samples longitudinally for analysis. While most patients had binding and neutralizing antibody titers that were comparable with healthy volunteers, 25% had poor responses, which led to six- to sevenfold lower titers than healthy controls. There was no association between worse vaccine responses and history of programmed death–1 monotherapy, chemotherapy, or both in combination. Receipt of a booster vaccine improved binding and neutralizing antibody titers to both the wild type and the Omicron variant, but 2-4 months after the booster there was a five- to sevenfold decrease in neutralizing titers to both the wild type and Omicron variant.

“This study indicates both the need to monitor our patients with lung cancer for response to COVID-19 mRNA vaccines, identify the nonresponders for follow-up and further attempts at immunization, and continue collecting and analyzing clinicodemographic information and biospecimens from our patients,” wrote the authors of an accompanying editorial.

Although the findings reveal potential concerns, the good news is that most patients NSCLC patients do respond normally to COVID-19 vaccination, said John D. Minna, MD, University of Texas Southwestern Medical Center, Dallas, lead author of the editorial.

He offered some advice to physicians. “You can test your patients using currently available [Clinical Laboratory Improvement Amendments]–approved lab tests to determine what their antibody titers are. This should be done after boosting since titers will go down after time. We know that if a patient has lung cancer and they do get infected with SARS-CoV-2 that potentially they could develop serious COVID-19 disease. Besides giving antiviral treatment, it is important that they be closely monitored for symptoms of progression so if they need to be hospitalized it can be done in a prudent manner,” said Dr. Minna, who is director of the Hamon Center for Therapeutic Oncology Research at the University of Texas Southwestern Medical Center.

No clinical details have emerged that might predict which patients have an insufficient response to vaccination. “When we started these studies, a lot of us thought that anyone who did not develop a good antibody response would be weak or sicker. For example, [patients with] late-stage disease, or having had a lot of therapy, or perhaps immune checkpoint blockade. However, none of these things are correlated. The main advice we are giving our lung cancer patients are to get vaccinated, get boosted (double boosted), and just do the smart thing to protect yourself from exposure,” he said.

For example, when traveling on a plane, patients should wear a mask. They should also avoid large indoor events. He also recommended that, following vaccination and boosters, patients seek out CLIA-certified tests to get their titer checked.

“Upon any COVID infection, even if their titer is at or above 80%, patients should see their physician to consider treatment with Paxlovid (nirmatrelvir/ritonavir), which has emergency use authorization. For patients with a lower titer, it’s important to seek out a physician and consider Paxlovid and possibly antibody therapy. But these are individual decisions to be made with your doctor,” Dr. Minna said.

The next important research question is what happens to T-cell immune response following vaccination. “We know that a good cellular immune response is also important in preventing infection and severe infection, but we don’t yet know which persons (with or without cancer) have good T-cell responses. This information will also likely impact what we tell our patients and will add to the antibody data,” he said.

Studies are ongoing to determine specific T-cell responses to mRNA vaccines, and how well those T-cell responses respond to SARS-CoV-2 infection in the laboratory.

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

Richard Martinello, MD, a professor of medicine and pediatric infectious diseases at Yale University, New haven, Conn., doesn’t expect to see a child hospitalized with respiratory syncytial virus (RSV) in the middle of summer. The illness, which can strike infants and older adults especially hard, is known as a “winter virus.”

But not this year. Over the last several weeks, he says, admissions for children with RSV have increased at the Yale New Haven Children’s Hospital. While the numbers aren’t large, they are out of the ordinary, he says, “because usually, at this time of year, we see zero. For lack of a better term, it’s weird.”

Likewise, William Schaffner, MD, a professor of infectious diseases at Vanderbilt University in Nashville, says RSV is on the rise there. Tennessee is one of 10 states taking part in a Centers for Disease Control and Prevention surveillance system that tracks influenza, RSV, and COVID-19.

He says RSV cases have risen by at least a third during the past week, including all age ranges. At this time of year, he says, “We aren’t supposed to have any RSV.”

RSV isn’t the only virus thriving out of season or otherwise acting strangely. Since the pandemic began, flu seasons have been out of whack – sometimes nearly nonexistent and other times extending well beyond “normal” seasons. Some experts say one influenza “B” strain may now be extinct, while others say it will be back.

Severe colds – what some call “super colds” – also seem to be on the rise in recent warm-weather months, although that evidence is mostly based on personal experience, not science.

Trying to explain these out-of-season variations has sparked much discussion among epidemiologists and virologists, Dr. Schaffner says, with debates ongoing about whether human behavior and habits or the seasons play a bigger role in the transmission of viral illness.

On top of that, scientists are also looking at the interactions between the SARS-CoV-2 virus that causes COVID-19 and other viruses. When people get hit with COVID-19 and other viruses at the same time, does that make COVID-19 more severe, or less?

Research is conflicting.
 

Summer of 2022: A repeat of 2021?

RSV. Most children contract the virus by age 2, and while it’s generally mild, about 58,000 children under age 5 years are hospitalized each year. During the pandemic, RSV cases decreased from January to April 2020, the CDC reported, and then remained at “historically low levels”: less than 1% positive RSV results a week, for the next year.

But cases began rising in April 2021.

“Last year, we did have an unusual summer,” Dr. Schaffner says. After lockdown ended, to everyone’s surprise, RSV infections rose.

That increase triggered a CDC health advisory in June 2021, telling doctors and caregivers about the increase in “interseasonal” RSV cases across parts of the Southern United States, recommending broader testing for RSV in patients who had a respiratory illness but tested negative for COVID.

Because of the reduced circulation of RSV during the winter of 2020 to 2021, the CDC warned, older infants and toddlers might have a higher risk of RSV since they weren’t exposed to typical levels of RSV for the previous 15 months.

What about 2022? “At the moment,” Dr. Schaffner says, “it looks like we are having a repeat [of 2021].”

On Twitter, other pediatricians, including those from Maine and Texas, have reported an increase in RSV cases this summer.

Influenza. From October 2020 until May 2021, flu activity was lower than during any previous flu season since at least 1997, according to the CDC.

In late 2021, researchers suggested that one line of influenza known as B/Yamagata may have become extinct.

The 2021-2022 flu season has been mild, the CDC says, but it has come in two waves, with the second wave lingering longer than previous ones. While flu activity is decreasing, last week the CDC said doctors should be alert to flu infections throughout the summer.

Colds. In reports on colds that aren’t based on science, several doctors say they are seeing more colds than usual in the summer, and they’re more severe than usual. According to the CDC, common coronaviruses and respiratory adenoviruses have been increasing since early 2021, and rhinoviruses since June 2020.

Behavior vs. seasons

In explaining the spread of viral respiratory diseases, infectious disease doctors consider two things. “One is that temperature and humidity in the winter favors longer survival of some viruses, leading to longer periods of possible transmission,” says Dean Blumberg, MD, a professor of pediatrics and chief of pediatric infectious disease at University of California Davis Health.

“The other is differences in human behavior, with people spending more time outside in the summer, which results in more distancing and [less] virus concentration due to very large air volume,” he says, and vice versa in winter.

What about the “super colds?” COVID-19 lockdowns and social distancing greatly reduced people’s exposure to common viruses like those that cause colds, says Neil A. Mabbott, PhD, a professor of immunopathology at the University of Edinburgh (Scotland).

“Immunity to these common cold viruses gained through natural infection is considered to last around 8 or 9 months or so,” he says. “Each winter, when we are exposed to the new circulating variants of these viruses, our immunity receives a natural boost.”

That explains why most people get a cold that’s relatively mild. But with all the pandemic lockdowns and the use of hand sanitizers, most people had limited exposure to other viruses, including the common cold. When people emerged from lockdown, the common cold viruses were beginning to circulate again.

“Our immune systems were less able to clear the infection than previously,” Dr. Mabbott says. “As a consequence, some may have experienced increased symptoms, giving the impression of being infected with a ‘super cold.’ ”

“The colds themselves are probably not different to those we got prepandemic,” says Ian Mackay, PhD, a virologist at the University of Queensland, Brisbane, Australia. “But there might be more of them. So I doubt they are ‘super colds’ as much as they are ‘super-perfect circumstances.’ ”

The colds themselves are probably not different to those we got prepandemic. But there might be more of them.

Those super-perfect circumstances, he says, include people gathering after lockdown; a lack of immunity in new babies; viruses that have remained, even if at low levels, but continue to mutate; and our waning immunity to the range of viruses we’d normally encounter.

While lack of exposure may partly explain why some viruses become rampant out of season, it’s likely not the only reason. For example, the reduced circulation of RSV in the population as a whole also may have reduced the transfer of immunity from mothers to infants, some researchers say, making those infants more vulnerable than usual.
 

Interactions of viruses

Another thing that may be driving the different behavior of viruses is that the SARS-CoV-2 virus could somehow be interacting with other respiratory viruses, Dr. Schaffner says. “And if so, what sort of interactions?”

Many researchers are looking into that, and how coinfections with other respiratory diseases, including the common cold and flu, may affect the course of COVID-19. Some studies have found that the T cells – a source of deeper, cellular immunity in people – generated after a common cold “may also provide cross-protection in some people against COVID-19.”

But another study found immunity against common cold–causing coronaviruses might make COVID-19 more severe.

When researchers in the United Kingdom studied nearly 7,000 patients infected with COVID-19, including 583 also infected with RSV, flu, or adenoviruses (causing flulike or coldlike illness), those with flu or adenovirus, compared with the others, were at higher risk of death.
 

To be continued …

Exactly how COVID-19 will be changing what we know of other viruses is yet to be determined, too.

Even before the pandemic, Dr. Martinello says, there were already some shifts in RSV. Florida, for instance, has an RSV season longer than the rest of the country, mimicking the pattern in the tropics.

Will the atypical patterns continue? “My guess is that this will settle out,” he says, with some sort of pattern developing. At this point, there are many unknowns. “We still can’t answer whether there will be some seasonality to COVID.”

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

The combination of a tyrosine kinase inhibitor with an immune checkpoint inhibitor significantly improved progression-free survival in patients with hepatocellular carcinoma, shows a new study.

While the combination has been shown to be beneficial in renal cell carcinoma and other solid tumor types, it has never before been tested in a phase 3 clinical trial for hepatocellular carcinoma until now.

The new study, published in The Lancet Oncology, included 837 patients from 178 hospital in 32 countries who were enrolled in the study (called COSMIC-312) between December 2018 and August 2020. 432 patients were randomly assigned to receive a combination of cabozantinib (Cabometyx, Exelixis), a tyrosine kinase inhibitor (TKI), and atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor. While 217 patients were treated with sorafenib (Nexavar, Bayer) alone and 188 patients were treated with cabozantinib.

Clinically meaningful improvements in progression-free survival, increased disease control and lower primary progression were seen in patients who received the cabozantinib and atezolizumab combination therapy over patients who were treated with sorafenib. However, there was no improvement in overall survival.

“The improvement in progression-free survival with cabozantinib plus atezolizumab in this study shows that the combination confers clinical benefit for patients with advanced hepatocellular carcinoma previously untreated with systemic anticancer therapy,” wrote the authors of the study, led by Robin Kate Kelley, MD, a gastrointestinal oncologist with the University of California, San Francisco, and Lorenza Rimassa, MD, a gastrointestinal oncologist with Humanitas University, Milan. “The absence of a benefit in overall survival, along with the availability of atezolizumab in combination with bevacizumab, indicates the need for additional studies to determine if cabozantinib plus atezolizumab would be an appropriate first-line treatment option in select patient populations.”

For symptomatic patients with high disease burden or main portal vein occlusion who are at risk for impending complications, controlling the disease as quickly as possible is vital, the authors wrote. “Underlying chronic liver disease is nearly universal in patients with hepatocellular carcinoma and the risk of gastrointestinal bleeding is high in this population, particularly if portal vein tumor thrombus is present.”

Hepatocellular carcinoma (HCC) is an angiogenic tumor, making it a logical target for TKIs that target vascular endothelial growth factor. The TKI sorafenib was the first to be approved as a first-line treatment for HCC, and since then immune checkpoint inhibitors have been shown to induce durable responses in the first-line setting, but have not improved overall survival in randomized trials.
 

Study methodology

In the study, after a median follow-up of 15.8 months, median progression-free survival was 6.8 months in the combination group and 4.2 months in the sorafenib group (hazard ratio, 0.63; P = .0012). The median overall survival was 15.4 months in the combination group and 15.5 months in the sorafenib group (not significant). Grade 3-4 adverse events included an increase in ALT, which occurred in 9% of the combination group, 3% of the sorafenib group, and 6% of the cabozantinib only group; hypertension (9%, 8%, and 12%, respectively); an increase in AST increase (9%, 4%, 10%); and palmar-plantar erythrodysesthesia (8%, 8%, 9%). Serious treatment-related adverse events occurred in 18% of patients in the combination arm, 8% in the sorafenib arm, and 13% in the cabozantinib arm.

There were no excess serious bleeding events in the treatment groups containing cabozantinib, compared with sorafenib which is noteworthy because HCC patients are at high risk for gastrointestinal bleeding.

Treatment-related grade 5 events were rare, occurring in 1% (six patients) of the combination group, and in just one patient in both the sorafenib and cabozantinib groups.

Although the results suggest promising clinical benefit, the lack of overall survival benefit limit the implications of these findings. Since atezolizumab combined with bevacizumab is also available for this patient population, more research is needed to determine if cabozantinib plus atezolizumab can become a first-line option.

The study had some limitations: Participants had to have a Child-Pugh class of A, though there was no requirement to assess for fibrosis or cirrhosis. Otherwise there were few barriers to study entry.

The study was sponsored by Exelixis (Alameda) and Ipsen (Boulogne-Billancourt, France).

The combination of a tyrosine kinase inhibitor with an immune checkpoint inhibitor significantly improved progression-free survival in patients with hepatocellular carcinoma, shows a new study.

While the combination has been shown to be beneficial in renal cell carcinoma and other solid tumor types, it has never before been tested in a phase 3 clinical trial for hepatocellular carcinoma until now.

The new study, published in The Lancet Oncology, included 837 patients from 178 hospital in 32 countries who were enrolled in the study (called COSMIC-312) between December 2018 and August 2020. 432 patients were randomly assigned to receive a combination of cabozantinib (Cabometyx, Exelixis), a tyrosine kinase inhibitor (TKI), and atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor. While 217 patients were treated with sorafenib (Nexavar, Bayer) alone and 188 patients were treated with cabozantinib.

Clinically meaningful improvements in progression-free survival, increased disease control and lower primary progression were seen in patients who received the cabozantinib and atezolizumab combination therapy over patients who were treated with sorafenib. However, there was no improvement in overall survival.

“The improvement in progression-free survival with cabozantinib plus atezolizumab in this study shows that the combination confers clinical benefit for patients with advanced hepatocellular carcinoma previously untreated with systemic anticancer therapy,” wrote the authors of the study, led by Robin Kate Kelley, MD, a gastrointestinal oncologist with the University of California, San Francisco, and Lorenza Rimassa, MD, a gastrointestinal oncologist with Humanitas University, Milan. “The absence of a benefit in overall survival, along with the availability of atezolizumab in combination with bevacizumab, indicates the need for additional studies to determine if cabozantinib plus atezolizumab would be an appropriate first-line treatment option in select patient populations.”

For symptomatic patients with high disease burden or main portal vein occlusion who are at risk for impending complications, controlling the disease as quickly as possible is vital, the authors wrote. “Underlying chronic liver disease is nearly universal in patients with hepatocellular carcinoma and the risk of gastrointestinal bleeding is high in this population, particularly if portal vein tumor thrombus is present.”

Hepatocellular carcinoma (HCC) is an angiogenic tumor, making it a logical target for TKIs that target vascular endothelial growth factor. The TKI sorafenib was the first to be approved as a first-line treatment for HCC, and since then immune checkpoint inhibitors have been shown to induce durable responses in the first-line setting, but have not improved overall survival in randomized trials.
 

Study methodology

In the study, after a median follow-up of 15.8 months, median progression-free survival was 6.8 months in the combination group and 4.2 months in the sorafenib group (hazard ratio, 0.63; P = .0012). The median overall survival was 15.4 months in the combination group and 15.5 months in the sorafenib group (not significant). Grade 3-4 adverse events included an increase in ALT, which occurred in 9% of the combination group, 3% of the sorafenib group, and 6% of the cabozantinib only group; hypertension (9%, 8%, and 12%, respectively); an increase in AST increase (9%, 4%, 10%); and palmar-plantar erythrodysesthesia (8%, 8%, 9%). Serious treatment-related adverse events occurred in 18% of patients in the combination arm, 8% in the sorafenib arm, and 13% in the cabozantinib arm.

There were no excess serious bleeding events in the treatment groups containing cabozantinib, compared with sorafenib which is noteworthy because HCC patients are at high risk for gastrointestinal bleeding.

Treatment-related grade 5 events were rare, occurring in 1% (six patients) of the combination group, and in just one patient in both the sorafenib and cabozantinib groups.

Although the results suggest promising clinical benefit, the lack of overall survival benefit limit the implications of these findings. Since atezolizumab combined with bevacizumab is also available for this patient population, more research is needed to determine if cabozantinib plus atezolizumab can become a first-line option.

The study had some limitations: Participants had to have a Child-Pugh class of A, though there was no requirement to assess for fibrosis or cirrhosis. Otherwise there were few barriers to study entry.

The study was sponsored by Exelixis (Alameda) and Ipsen (Boulogne-Billancourt, France).

The combination of a tyrosine kinase inhibitor with an immune checkpoint inhibitor significantly improved progression-free survival in patients with hepatocellular carcinoma, shows a new study.

While the combination has been shown to be beneficial in renal cell carcinoma and other solid tumor types, it has never before been tested in a phase 3 clinical trial for hepatocellular carcinoma until now.

The new study, published in The Lancet Oncology, included 837 patients from 178 hospital in 32 countries who were enrolled in the study (called COSMIC-312) between December 2018 and August 2020. 432 patients were randomly assigned to receive a combination of cabozantinib (Cabometyx, Exelixis), a tyrosine kinase inhibitor (TKI), and atezolizumab (Tecentriq, Genentech), a PD-L1 inhibitor. While 217 patients were treated with sorafenib (Nexavar, Bayer) alone and 188 patients were treated with cabozantinib.

Clinically meaningful improvements in progression-free survival, increased disease control and lower primary progression were seen in patients who received the cabozantinib and atezolizumab combination therapy over patients who were treated with sorafenib. However, there was no improvement in overall survival.

“The improvement in progression-free survival with cabozantinib plus atezolizumab in this study shows that the combination confers clinical benefit for patients with advanced hepatocellular carcinoma previously untreated with systemic anticancer therapy,” wrote the authors of the study, led by Robin Kate Kelley, MD, a gastrointestinal oncologist with the University of California, San Francisco, and Lorenza Rimassa, MD, a gastrointestinal oncologist with Humanitas University, Milan. “The absence of a benefit in overall survival, along with the availability of atezolizumab in combination with bevacizumab, indicates the need for additional studies to determine if cabozantinib plus atezolizumab would be an appropriate first-line treatment option in select patient populations.”

For symptomatic patients with high disease burden or main portal vein occlusion who are at risk for impending complications, controlling the disease as quickly as possible is vital, the authors wrote. “Underlying chronic liver disease is nearly universal in patients with hepatocellular carcinoma and the risk of gastrointestinal bleeding is high in this population, particularly if portal vein tumor thrombus is present.”

Hepatocellular carcinoma (HCC) is an angiogenic tumor, making it a logical target for TKIs that target vascular endothelial growth factor. The TKI sorafenib was the first to be approved as a first-line treatment for HCC, and since then immune checkpoint inhibitors have been shown to induce durable responses in the first-line setting, but have not improved overall survival in randomized trials.
 

Study methodology

In the study, after a median follow-up of 15.8 months, median progression-free survival was 6.8 months in the combination group and 4.2 months in the sorafenib group (hazard ratio, 0.63; P = .0012). The median overall survival was 15.4 months in the combination group and 15.5 months in the sorafenib group (not significant). Grade 3-4 adverse events included an increase in ALT, which occurred in 9% of the combination group, 3% of the sorafenib group, and 6% of the cabozantinib only group; hypertension (9%, 8%, and 12%, respectively); an increase in AST increase (9%, 4%, 10%); and palmar-plantar erythrodysesthesia (8%, 8%, 9%). Serious treatment-related adverse events occurred in 18% of patients in the combination arm, 8% in the sorafenib arm, and 13% in the cabozantinib arm.

There were no excess serious bleeding events in the treatment groups containing cabozantinib, compared with sorafenib which is noteworthy because HCC patients are at high risk for gastrointestinal bleeding.

Treatment-related grade 5 events were rare, occurring in 1% (six patients) of the combination group, and in just one patient in both the sorafenib and cabozantinib groups.

Although the results suggest promising clinical benefit, the lack of overall survival benefit limit the implications of these findings. Since atezolizumab combined with bevacizumab is also available for this patient population, more research is needed to determine if cabozantinib plus atezolizumab can become a first-line option.

The study had some limitations: Participants had to have a Child-Pugh class of A, though there was no requirement to assess for fibrosis or cirrhosis. Otherwise there were few barriers to study entry.

The study was sponsored by Exelixis (Alameda) and Ipsen (Boulogne-Billancourt, France).

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

The Diagnosis: Plaque-type Syringoma

A biopsy demonstrated multiple basaloid islands of tumor cells in the reticular dermis with ductal differentiation, some with a commalike tail. The ducts were lined by 2 to 3 layers of small uniform cuboidal cells without atypia and contained inspissated secretions within the lumina of scattered ducts. There was an associated fibrotic collagenous stroma. There was no evidence of perineural invasion and no deep dermal or subcutaneous extension (Figure 1). Additional cytokeratin immunohistochemical staining highlighted the adnexal proliferation (Figure 2). A diagnosis of plaque-type syringoma (PTS) was made.

Syringomas are benign dermal sweat gland tumors that typically present as flesh-colored papules on the cheeks or periorbital area of young females. Plaque-type tumors as well as papulonodular, eruptive, disseminated, urticaria pigmentosa–like, lichen planus–like, or milialike syringomas also have been reported. Syringomas may be associated with certain medical conditions such as Down syndrome, Nicolau-Balus syndrome, and both scarring and nonscarring alopecias.¹ The clear cell variant of syringoma often is associated with diabetes mellitus.² Kikuchi et al³ first described PTS in 1979. Plaque-type syringomas rarely are reported in the literature, and sites of involvement include the head and neck region, upper lip, chest, upper extremities, vulva, penis, and scrotum.^4-6

Histologically, syringomatous lesions are composed of multiple small ducts lined by 2 to 3 layers of cuboidal epithelium. The ducts may be arranged in nests or strands of basaloid cells surrounded by a dense fibrotic stroma. Occasionally, the ducts will form a comma- or teardropshaped tail; however, this also may be observed in desmoplastic trichoepithelioma (DTE).⁷ Perineural invasion is absent in syringomas. Syringomas exhibit a lateral growth pattern that typically is limited to the upper half of the reticular dermis and spares the underlying subcutis, muscle, and bone. The growth pattern may be discontinuous with proliferations juxtaposed by normal-appearing skin.⁸ Syringomas usually express progesterone receptors and are known to proliferate at puberty, suggesting that these neoplasms are under hormonal control.⁹ Although syringomas are benign, various treatment options that may be pursued for cosmetic purposes include radiofrequency, staged excision, laser ablation, and oral isotretinoin.^8,10 If only a superficial biopsy is obtained, syringomas may display features of other adnexal neoplasms, including microcystic adnexal carcinoma (MAC), DTE, morpheaform basal cell carcinoma (BCC), and inflammatory linear verrucous epidermal nevus (ILVEN).

Microcystic adnexal carcinoma is a locally aggressive neoplasm first described by Goldstein et al¹¹ in 1982 an indurated, ill-defined plaque or nodule on the face with a predilection for the upper and lower lip. Prior radiation therapy and immunosuppression are risk factors for the development of MAC.¹² Histologically, the superficial portion displays small cornifying cysts interspersed with islands of basaloid cells and may mimic a syringoma. However, the deeper portions demonstrate ducts lined by a single layer of cells with a background of hyalinized and sclerotic stroma. The tumor cells may occupy the deep dermis and underlying subcutis, muscle, or bone and demonstrate an infiltrative growth pattern and perineural invasion. Treatment includes Mohs micrographic surgery.

Desmoplastic trichoepitheliomas most commonly present as solitary white to yellowish annular papules or plaques with a central dell located on sun-exposed areas of the face, cheeks, or chin. This benign neoplasm has a bimodal age distribution, primarily affecting females either in childhood or adulthood.¹³ Histologically, strands and nests of basaloid epithelial cells proliferate in a dense eosinophilic desmoplastic stroma. The basaloid islands are narrow and cordlike with growth parallel to the surface epidermis and do not dive deeply into the deep dermis or subcutis. Ductal differentiation with associated secretions typically is not seen in DTE.¹ Calcifications and foreign body granulomatous infiltrates may be present. Merkel cells also are present in this tumor and may be highlighted by immunohistochemistry with cytokeratin 20.¹⁴ Rarely, desmoplastic trichoepitheliomas may transform into trichoblastic carcinomas. Treatment may consist of surgical excision or Mohs micrographic surgery.

Morpheaform BCC also is included in the clinical and histopathologic differential diagnosis of infiltrative basaloid neoplasms. It is one of the more aggressive variants of BCC. The use of immunohistochemical staining may aid in differentiating between these sclerosing adnexal neoplasms.¹⁵ For example, pleckstrin homologylike domain family A member 1 (PHLDA1) is a stem cell marker that is heavily expressed in DTE as a specific follicular bulge marker but is not present in a morpheaform BCC. This highlights the follicular nature of DTEs at the molecular level. BerEP4 is a monoclonal antibody that serves as an epithelial marker for 2 glycopolypeptides: 34 and 39 kDa. This antibody may demonstrate positivity in morpheaform BCC but does not stain cells of interest in MAC.

Inflammatory linear verrucous epidermal nevus clinically presents with erythematous and warty papules in a linear distribution following the Blaschko lines. The papules often are reported to be intensely pruritic and usually are localized to one extremity.¹⁶ Although adultonset forms of ILVEN have been described,¹⁷ it most commonly is diagnosed in young children. Histologically, ILVEN consists of psoriasiform epidermal hyperplasia with alternating areas of parakeratosis and orthokeratosis with underlying agranulosis and hypergranulosis, respectively.¹⁸ The upper dermis contains a perivascular lymphocytic infiltrate. Treatment with laser therapy and surgical excision has led to both symptomatic and clinical improvement of ILVEN.¹⁶

Plaque-type syringomas are a rare variant of syringomas that clinically may mimic other common inflammatory and neoplastic conditions. An adequate biopsy is imperative to differentiate between adnexal neoplasms, as a small superficial biopsy of a syringoma may demonstrate features observed in other malignant or locally aggressive neoplasms. In our patient, the small ducts lined by cuboidal epithelium with no cellular atypia and no deep dermal growth or perineural invasion allowed for the diagnosis of PTS. Therapeutic options were reviewed with our patient, including oral isotretinoin, laser therapy, and staged excision. Ultimately, our patient elected not to pursue treatment, and she is being monitored clinically for any changes in appearance or symptoms.

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

There is evidence that gout and heart disease are mechanistically linked by inflammation and patients with gout are at elevated risk for cardiovascular disease (CVD). But do gout flares, on their own, affect short-term risk for CV events? A new analysis based on records from British medical practices suggests that might be the case.

Risk for myocardial infarction or stroke climbed in the weeks after individual gout flare-ups in the study’s more than 60,000 patients with a recent gout diagnosis. The jump in risk, significant but small in absolute terms, held for about 4 months in the case-control study before going away.

A sensitivity analysis that excluded patients who already had CVD when their gout was diagnosed yielded similar results.

The observational study isn’t able to show that gout flares themselves transiently raise the risk for MI or stroke, but it’s enough to send a cautionary message to physicians who care for patients with gout, rheumatologist Abhishek Abhishek, PhD, Nottingham (England) City Hospital, said in an interview.

In such patients who also have conditions like hypertension, diabetes, or dyslipidemia, or a history of heart disease, he said, it’s important “to manage risk factors really aggressively, knowing that when these patients have a gout flare, there’s a temporary increase in risk of a cardiovascular event.”

Managing their absolute CV risk – whether with drug therapy, lifestyle changes, or other interventions – should help limit the transient jump in risk for MI or stroke following a gout flare, proposed Dr. Abhishek, who is senior author on the study published in JAMA, with lead author Edoardo Cipolletta, MD, also from Nottingham City Hospital.

First robust evidence

The case-control study, which involved more than 60,000 patients with a recent gout diagnosis, some who went on to have MI or stroke, looked at rates of such events at different time intervals after gout flares. Those who experienced such events showed a more than 90% increased likelihood of a gout flare-up in the preceding 60 days, a greater than 50% chance of a flare between 60 and 120 days before the event, but no increased likelihood prior to 120 days before the event.

Such a link between gout flares and CV events “has been suspected but never proven,” observed rheumatologist Hyon K. Choi, MD, Harvard Medical School, Boston, who was not associated with the analysis. “This is the first time it has actually been shown in a robust way,” he said in an interview.

The study suggests a “likely causative relationship” between gout flares and CV events, but – as the published report noted – has limitations like any observational study, said Dr. Choi, who also directs the Gout & Crystal Arthropathy Center at Massachusetts General Hospital, Boston. “Hopefully, this can be replicated in other cohorts.”

The analysis controlled for a number of relevant potential confounders, he noted, but couldn’t account for all issues that could argue against gout flares as a direct cause of the MIs and strokes.

Gout attacks are a complex experience with a range of potential indirect effects on CV risk, Dr. Choi observed. They can immobilize patients, possibly raising their risk for thrombotic events, for example. They can be exceptionally painful, which causes stress and can lead to frequent or chronic use of glucocorticoids or NSAIDs, all of which can exacerbate high blood pressure and possibly worsen CV risk.
 

A unique insight

The timing of gout flares relative to acute vascular events hasn’t been fully explored, observed an accompanying editorial. The current study’s “unique insight,” it stated, “is that disease activity from gout was associated with an incremental increase in risk for acute vascular events during the time period immediately following the gout flare.”

Although the study is observational, a “large body of evidence from animal and human research, mechanistic insights, and clinical interventions” support an association between flares and vascular events and “make a causal link eminently reasonable,” stated the editorialists, Jeffrey L. Anderson, MD, and Kirk U. Knowlton, MD, both with Intermountain Medical Center, Salt Lake City, Utah.

The findings, they wrote, “should alert clinicians and patients to the increased cardiovascular risk in the weeks beginning after a gout flare and should focus attention on optimizing preventive measures.” Those can include “lifestyle measures and standard risk-factor control including adherence to diet, statins, anti-inflammatory drugs (e.g., aspirin, colchicine), smoking cessation, diabetic and blood pressure control, and antithrombotic medications as indicated.”

Dr. Choi said the current results argue for more liberal use of colchicine, and for preferring colchicine over other anti-inflammatories, in patients with gout and traditional CV risk factors, given multiple randomized trials supporting the drug’s use in such cases. “If you use colchicine, you are covering their heart disease risk as well as their gout. It’s two birds with one stone.”
 

Nested case-control study

The investigators accessed electronic health records from 96,153 patients with recently diagnosed gout in England from 1997 to 2020; the cohort’s mean age was about 76 years, and 69% of participants were men. They matched 10,475 patients with at least one CV event to 52,099 others who didn’t have such an event by age, sex, and time from gout diagnosis. In each matched set of patients, those not experiencing a CV event were assigned a flare-to-event interval based on their matching with patients who did experience such an event.

Those with CV events, compared with patients without an event, had a greater than 90% increased likelihood of experiencing a gout flare-up in the 60 days preceding the event, a more than 50% greater chance of a flare-up 60-120 days before the CV event, but no increased likelihood more than 120 days before the event.

A self-controlled case series based on the same overall cohort with gout yielded similar results while sidestepping any potential for residual confounding, an inherent concern with any case–control analysis, the report notes. It involved 1,421 patients with one or more gout flare and at least one MI or stroke after the diagnosis of gout.

Among that cohort, the CV-event incidence rate ratio, adjusted for age and season of the year, by time interval after a gout flare, was 1.89 (95% confidence interval, 1.54-2.30) at 0-60 days, 1.64 (95% CI, 1.45-1.86) at 61-120 days, and1.29 (95% CI, 1.02-1.64) at 121-180 days.

Also similar, the report noted, were results of several sensitivity analyses, including one that excluded patients with confirmed CVD before their gout diagnosis; another that left out patients at low to moderate CV risk; and one that considered only gout flares treated with colchicine, corticosteroids, or NSAIDs.

The incremental CV event risks observed after flares in the study were small, which “has implications for both cost effectiveness and clinical relevance,” observed Dr. Anderson and Dr. Knowlton.

“An alternative to universal augmentation of cardiovascular risk prevention with therapies among patients with gout flares,” they wrote, would be “to further stratify risk by defining a group at highest near-term risk.” Such interventions could potentially be guided by markers of CV risk such as, for example, levels of high-sensitivity C-reactive protein or lipoprotein(a), or plaque burden on coronary-artery calcium scans.

Dr. Abhishek, Dr. Cipolletta, and the other authors reported no competing interests. Dr. Choi disclosed research support from Ironwood and Horizon; and consulting fees from Ironwood, Selecta, Horizon, Takeda, Kowa, and Vaxart. Dr. Anderson disclosed receiving grants to his institution from Novartis and Milestone.

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

High oral cavity doses of radiotherapy are associated with greater risk of taste dysfunction in patients with head and neck cancer, finds a new study from JAMA Otolaryngology–Head & Neck Surgery.

Taste dysfunction can affect up to 90% of patients undergoing radiotherapy for head and neck cancer. While the ability to taste usually returns after the treatment concludes, some patients can still feel the lingering effects of radiotherapy on taste function long after the treatment concludes. It can lead to weight loss and dry mouth which can, in turn, negatively affect quality of life.

“Taste dysfunction has profound effects on quality of life in patients with head and neck cancer, and the oral cavity dose could be significantly lower with modern radiotherapy techniques,” wrote the researchers, who were led by Miao-Fen Chen, MD, PhD, of Chang Gung University, Taoyuan City, Taiwan. “This study provides useful dose constraints of the oral cavity that may be associated with reduced taste dysfunction.”

Degradation of taste is an important quality of life factor for head and neck cancer patients. A 2021 systematic review published in the journal Radiotherapy and Oncology found that acute taste dysfunction affected 96% of patients as measured objectively, and 79% as measured subjectively. While most patients recover an estimated 23-53% of patients experience long-term dysfunction.

In 2019, a study published in the journal Chemical Senses found that 31% of head and neck cancer patients had long-term changes to taste at 27 months after intensity-modulated radiotherapy (IMRT), with dysfunction associated with glossectomy and oral cavity radiation doses greater than 50 Gy, but the study only used one quality of life subjective measure to evaluate taste function.

In the new JAMA study, researchers reported the results of a longitudinal using the whole-mouth solution method for basic tastes, including salt, sweet, sour, and bitter.
 

Study methodology

The study included 87 patients (mean age, 58 years; 90% men) who were enrolled between 2017 and 2020 from a single hospital. 45 patients received primary intensity-modulated radiotherapy and 42 received postoperative radiotherapy. 78 patients received volumetric arc therapy, and 9 received intensity-modulated radiotherapy. The radiotherapy was directed to minimize the effect on the parotid glands and oral cavity.

Researchers measured taste dysfunction according to detection thresholds based on solutions with different concentrations. After moving the solution around the mouth and spitting it out, patients were asked to identify taste components. Following a water rinse, they tested a solution with another concentration of taste components. A number was assigned based on the concentration level they were able to detect, with nigher numbers indicating greater sensitivity.

Two to four weeks after initiation of radiotherapy, there were drops in taste scores for salt (4.7 to 1.4), sweet (4.2 to 1.8), sour (4.5 to 2.3), and bitter (4.7 to 1.2). 1 week after radiotherapy, those mean scores increased to 2.6, 2.6, 2.9, and 2.3 respectively. Over the following 3 months, mean scores reflected general recovery to near preradiotherapy levels (4.2, 3.9, 4.1, and 4.0, respectively). At 6 months and 1 year, the scores were equivalent to preradiotherapy levels.

Objective taste tests were performed on 81 participants. 33.3% had taste dysfunction 6 months after radiotherapy. 6 months after, 8.9% had taste dysfunction. At 3 months following radiotherapy, taste dysfunction was associated with an oral cavity mean dose of 4,000 cGy or higher (relative risk, 2.87; 95% confidence interval, 1.21-6.81) or 5,000 cGy or higher (RR, 2.04; 95% CI, 1.12-3.72). At 6 months, taste dysfunction was predicted by glossectomy (RR, 5.63; 95% CI, 1.12-28.15) and oral cavity mean dose 5,000 cGy or greater (RR, 7.79; 95% CI, 0.93-64.92).

The researchers quantified the relationship between mean oral cavity dose and probability of developing taste dysfunction at 3 and 6 months. 3 months after radiotherapy, 25 Gy predicted a 15% chance, 38 Gy predicted a 25% chance, and 60 Gy predicted a 50% chance. At 6 months, the numbers were 57, 60, and 64 Gy.

The study was limited by being conducted at a single center and its small sample size, and it recruited patients varied significantly in treatment modality and disease subtype.

High oral cavity doses of radiotherapy are associated with greater risk of taste dysfunction in patients with head and neck cancer, finds a new study from JAMA Otolaryngology–Head & Neck Surgery.

Taste dysfunction can affect up to 90% of patients undergoing radiotherapy for head and neck cancer. While the ability to taste usually returns after the treatment concludes, some patients can still feel the lingering effects of radiotherapy on taste function long after the treatment concludes. It can lead to weight loss and dry mouth which can, in turn, negatively affect quality of life.

“Taste dysfunction has profound effects on quality of life in patients with head and neck cancer, and the oral cavity dose could be significantly lower with modern radiotherapy techniques,” wrote the researchers, who were led by Miao-Fen Chen, MD, PhD, of Chang Gung University, Taoyuan City, Taiwan. “This study provides useful dose constraints of the oral cavity that may be associated with reduced taste dysfunction.”

Degradation of taste is an important quality of life factor for head and neck cancer patients. A 2021 systematic review published in the journal Radiotherapy and Oncology found that acute taste dysfunction affected 96% of patients as measured objectively, and 79% as measured subjectively. While most patients recover an estimated 23-53% of patients experience long-term dysfunction.

In 2019, a study published in the journal Chemical Senses found that 31% of head and neck cancer patients had long-term changes to taste at 27 months after intensity-modulated radiotherapy (IMRT), with dysfunction associated with glossectomy and oral cavity radiation doses greater than 50 Gy, but the study only used one quality of life subjective measure to evaluate taste function.

In the new JAMA study, researchers reported the results of a longitudinal using the whole-mouth solution method for basic tastes, including salt, sweet, sour, and bitter.
 

Study methodology

The study included 87 patients (mean age, 58 years; 90% men) who were enrolled between 2017 and 2020 from a single hospital. 45 patients received primary intensity-modulated radiotherapy and 42 received postoperative radiotherapy. 78 patients received volumetric arc therapy, and 9 received intensity-modulated radiotherapy. The radiotherapy was directed to minimize the effect on the parotid glands and oral cavity.

Researchers measured taste dysfunction according to detection thresholds based on solutions with different concentrations. After moving the solution around the mouth and spitting it out, patients were asked to identify taste components. Following a water rinse, they tested a solution with another concentration of taste components. A number was assigned based on the concentration level they were able to detect, with nigher numbers indicating greater sensitivity.

Two to four weeks after initiation of radiotherapy, there were drops in taste scores for salt (4.7 to 1.4), sweet (4.2 to 1.8), sour (4.5 to 2.3), and bitter (4.7 to 1.2). 1 week after radiotherapy, those mean scores increased to 2.6, 2.6, 2.9, and 2.3 respectively. Over the following 3 months, mean scores reflected general recovery to near preradiotherapy levels (4.2, 3.9, 4.1, and 4.0, respectively). At 6 months and 1 year, the scores were equivalent to preradiotherapy levels.

Objective taste tests were performed on 81 participants. 33.3% had taste dysfunction 6 months after radiotherapy. 6 months after, 8.9% had taste dysfunction. At 3 months following radiotherapy, taste dysfunction was associated with an oral cavity mean dose of 4,000 cGy or higher (relative risk, 2.87; 95% confidence interval, 1.21-6.81) or 5,000 cGy or higher (RR, 2.04; 95% CI, 1.12-3.72). At 6 months, taste dysfunction was predicted by glossectomy (RR, 5.63; 95% CI, 1.12-28.15) and oral cavity mean dose 5,000 cGy or greater (RR, 7.79; 95% CI, 0.93-64.92).

The researchers quantified the relationship between mean oral cavity dose and probability of developing taste dysfunction at 3 and 6 months. 3 months after radiotherapy, 25 Gy predicted a 15% chance, 38 Gy predicted a 25% chance, and 60 Gy predicted a 50% chance. At 6 months, the numbers were 57, 60, and 64 Gy.

The study was limited by being conducted at a single center and its small sample size, and it recruited patients varied significantly in treatment modality and disease subtype.

High oral cavity doses of radiotherapy are associated with greater risk of taste dysfunction in patients with head and neck cancer, finds a new study from JAMA Otolaryngology–Head & Neck Surgery.

Taste dysfunction can affect up to 90% of patients undergoing radiotherapy for head and neck cancer. While the ability to taste usually returns after the treatment concludes, some patients can still feel the lingering effects of radiotherapy on taste function long after the treatment concludes. It can lead to weight loss and dry mouth which can, in turn, negatively affect quality of life.

“Taste dysfunction has profound effects on quality of life in patients with head and neck cancer, and the oral cavity dose could be significantly lower with modern radiotherapy techniques,” wrote the researchers, who were led by Miao-Fen Chen, MD, PhD, of Chang Gung University, Taoyuan City, Taiwan. “This study provides useful dose constraints of the oral cavity that may be associated with reduced taste dysfunction.”

Degradation of taste is an important quality of life factor for head and neck cancer patients. A 2021 systematic review published in the journal Radiotherapy and Oncology found that acute taste dysfunction affected 96% of patients as measured objectively, and 79% as measured subjectively. While most patients recover an estimated 23-53% of patients experience long-term dysfunction.

In 2019, a study published in the journal Chemical Senses found that 31% of head and neck cancer patients had long-term changes to taste at 27 months after intensity-modulated radiotherapy (IMRT), with dysfunction associated with glossectomy and oral cavity radiation doses greater than 50 Gy, but the study only used one quality of life subjective measure to evaluate taste function.

In the new JAMA study, researchers reported the results of a longitudinal using the whole-mouth solution method for basic tastes, including salt, sweet, sour, and bitter.
 

Study methodology

The study included 87 patients (mean age, 58 years; 90% men) who were enrolled between 2017 and 2020 from a single hospital. 45 patients received primary intensity-modulated radiotherapy and 42 received postoperative radiotherapy. 78 patients received volumetric arc therapy, and 9 received intensity-modulated radiotherapy. The radiotherapy was directed to minimize the effect on the parotid glands and oral cavity.

Researchers measured taste dysfunction according to detection thresholds based on solutions with different concentrations. After moving the solution around the mouth and spitting it out, patients were asked to identify taste components. Following a water rinse, they tested a solution with another concentration of taste components. A number was assigned based on the concentration level they were able to detect, with nigher numbers indicating greater sensitivity.

Two to four weeks after initiation of radiotherapy, there were drops in taste scores for salt (4.7 to 1.4), sweet (4.2 to 1.8), sour (4.5 to 2.3), and bitter (4.7 to 1.2). 1 week after radiotherapy, those mean scores increased to 2.6, 2.6, 2.9, and 2.3 respectively. Over the following 3 months, mean scores reflected general recovery to near preradiotherapy levels (4.2, 3.9, 4.1, and 4.0, respectively). At 6 months and 1 year, the scores were equivalent to preradiotherapy levels.

Objective taste tests were performed on 81 participants. 33.3% had taste dysfunction 6 months after radiotherapy. 6 months after, 8.9% had taste dysfunction. At 3 months following radiotherapy, taste dysfunction was associated with an oral cavity mean dose of 4,000 cGy or higher (relative risk, 2.87; 95% confidence interval, 1.21-6.81) or 5,000 cGy or higher (RR, 2.04; 95% CI, 1.12-3.72). At 6 months, taste dysfunction was predicted by glossectomy (RR, 5.63; 95% CI, 1.12-28.15) and oral cavity mean dose 5,000 cGy or greater (RR, 7.79; 95% CI, 0.93-64.92).

The researchers quantified the relationship between mean oral cavity dose and probability of developing taste dysfunction at 3 and 6 months. 3 months after radiotherapy, 25 Gy predicted a 15% chance, 38 Gy predicted a 25% chance, and 60 Gy predicted a 50% chance. At 6 months, the numbers were 57, 60, and 64 Gy.

The study was limited by being conducted at a single center and its small sample size, and it recruited patients varied significantly in treatment modality and disease subtype.

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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

The Food and Drug Administration has approved the dual interleukin-12 and IL-23 inhibitor ustekinumab (Stelara) for the treatment of juvenile psoriatic arthritis (jPsA) in patients aged 6 years and older, according to an Aug. 1 announcement from its manufacturer, Janssen.

The approval makes jPsA the sixth approved indication for ustekinumab, which include active psoriatic arthritis in adults, moderate to severe plaque psoriasis in both adults and children aged 6 years or older who are candidates for phototherapy or systemic therapy, moderately to severely active Crohn’s disease in adults, and moderately to severely active ulcerative colitis in adults.

In addition, ustekinumab is now the second biologic to be approved for jPsA, following the agency’s December 2021 approval of secukinumab (Cosentyx) to treat jPsA in children and adolescents aged 2 years and older as well as enthesitis-related arthritis in children and adolescents aged 4 years and older.

In pediatric patients, ustekinumab is administered as a subcutaneous injection dosed four times per year after two starter doses.

Ustekinumab’s approval is based on “an extrapolation of the established data and existing safety profile” of ustekinumab in multiple phase 3 studies in adult and pediatric patients with moderate to severe plaque psoriasis and adult patients with active PsA, according to Janssen.

“With the limited availability of pediatric patients for clinical trial inclusion, researchers can extrapolate data from trials with adults to determine the potential efficacy and tolerability of a treatment for a pediatric population,” according to the October 2021 announcement from the company that the Biologics License Application had been submitted to the FDA.

Juvenile arthritis occurs in an estimated 20-45 children per 100,000 in the United States, with about 5% of those children having jPsA, according to the National Psoriasis Foundation.

The prescribing information for ustekinumab includes specific warnings and areas of concern. The drug should not be administered to individuals with known hypersensitivity to ustekinumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, sometimes serious, and a test for tuberculosis infection should be given before administration.

Patients taking ustekinumab should not be given a live vaccine, and their doctors should be informed if anyone in their household needs a live vaccine. They also should not receive the BCG vaccine during the 1 year before receiving the drug or 1 year after they stop taking it, according to Johnson & Johnson.

The most common adverse effects include nasal congestion, sore throat, runny nose, upper respiratory infections, fever, headache, tiredness, itching, nausea and vomiting, redness at the injection site, vaginal yeast infections, urinary tract infections, sinus infection, bronchitis, diarrhea, stomach pain, and joint pain.

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