PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

PHOENIX – A liquid biopsy test may accurately predict recurrence of human papillomavirus (HPV)–driven oropharyngeal squamous cell carcinoma (OPSCC) earlier than standard clinical and imaging assessments, a new analysis indicates.

Of 80 patients who tested positive for circulating tumor tissue–modified viral (TTMV)-HPV DNA during surveillance, 74% (n = 59) had no other evidence of disease or had indeterminate disease status.

And of those patients, 93% (n = 55) “later had proven recurrent, metastatic disease on imaging and/or biopsy,” according to Glenn Hanna, MD, from the Dana-Farber Cancer Institute, Boston, who presented the results Feb. 24 at the 2022 Multidisciplinary Head and Neck Cancers Symposium.

“This is the first study to demonstrate broad clinical utility and validity of the biomarker in HPV-driven oropharyngeal cancer,” Dr. Hanna said in a press release.

Although patients with HPV-driven OPSCC generally have favorable outcomes, up to 25% will experience recurrence after treatment.

Post-treatment surveillance currently relies on physical examinations and imaging, but Dr. Hanna and colleagues wanted to determine whether a routine circulating cell-free TTMV-HPV DNA test could detect occult recurrence sooner.

Dr. Hanna and colleagues analyzed the records of 1,076 patients with HPV-driven OPSCC at 118 sites in the U.S. who had completed therapy more than 3 months previously and undergone an TTMV-HPV DNA test (NavDx, Naveris) between June 2020 and November 2021.

The results of the test, which used ultrasensitive digital droplet PCR to identify HPV subtypes 16, 18, 31, 33, and 35, were compared with subsequent clinical evidence of OPSCC via nasopharyngolaryngoscopy, radiologic evaluations, or tissue biopsy.

Approximately 7% of the patients tested positive (n = 80) for circulating TTMV-HPV DNA. Of those, 26.2% (n = 21) had known clinical recurrence, while 73.8% (n = 59) had no other evidence of disease or an intermediate disease status.

Among those with no clinical evidence of recurrence, 93.2% (n = 55) had their recurrence subsequently confirmed using imaging or biopsy. Of the 4 remaining patients, 2 had clinically suspicious lesions, and 2 had no other evidence of disease.

Overall, the data indicate that the biomarker test demonstrated a 95% positive predictive value (76 of 80 patients) for recurrence or persistence of HPV-driven OPSCC.

According to Dr. Hanna, a positive TTMV-HPV DNA test was the first indicator of recurrence for 72% of patients, and almost half of recurrences were detected more than 12 months after completing therapy.

“Incorporating a test for TTMV-HPV DNA into routine post-treatment follow-up can enable physicians to detect recurrent cancers earlier and allow us to start recommended interventions more quickly to improve outcomes,” Dr. Hanna said in the release.

The study was supported by Naveris, which developed the TTMV-HPV DNA test studied. Dr. Hanna declares relationships with Actuate Therapeutics, Altor BioScience, Bicara, BMS, GSK, Merck, Regeneron, Sanofi/Genzyme, and others.

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

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

Among individuals with multiple sclerosis (MS), disease modifying therapies (DMTs) are associated with a reduced humoral response to SARS-CoV-2 vaccines, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.

“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.

The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.

The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.

After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.

The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).

The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).

Subanalyses by sex and vaccine type revealed no differences in nAb levels.

The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
 

Some answers, more questions

The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.

He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.

The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.

Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

Among individuals with multiple sclerosis (MS), disease modifying therapies (DMTs) are associated with a reduced humoral response to SARS-CoV-2 vaccines, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.

“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.

The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.

The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.

After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.

The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).

The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).

Subanalyses by sex and vaccine type revealed no differences in nAb levels.

The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
 

Some answers, more questions

The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.

He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.

The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.

Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

Among individuals with multiple sclerosis (MS), disease modifying therapies (DMTs) are associated with a reduced humoral response to SARS-CoV-2 vaccines, according to a new retrospective analysis. The link is particularly strong among B-cell depleting drugs.

“A lot of patients ask us if having MS by itself affects the vaccine response. We did not find that, but it’s about the disease-modifying therapy that a patient is being treated with,” Tirisham Gyang, MD, said in an interview. Dr. Gyang presented the study at a poster session during the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

“These patients (on DMTs) had decreased neutralizing antibody levels to the vaccine after they received it. We also saw a similar marker in drugs that modulate the sphingosine S-1 receptor. These patients also had a lower titer. It wasn’t statistically significant, but we think it’s positive. It was underpowered because there was a small number of patients in that subgroup,” said Dr. Gyang, assistant professor of neurology at The Ohio State University.

The results can inform vaccine strategies among people with MS, but the issue remains complex. “I don’t know that we could do a blanket statement and say, if you wait this amount of time, everybody will be okay. It’s a very individualized approach, and patients need to discuss timing of vaccines with their providers, because we know that waiting is better. It’s preferable to wait until towards the end of the dosing cycle. The other factor is making sure that the MS is well treated,” said Dr. Gyang.

The researchers prospectively followed 83 MS patients at the The Ohio State University Wexner Medical Center. Among the cohort, 71% were female. Fifty-one subjects had serum samples analyzed following mRNA COVID-19 vaccination, and they were compared with 38 health care worker controls.

After vaccination, people with MS had about 2.4-fold lower levels of half-maximal neutralization titer (NT50) values compared with health care worker controls. This appeared to be driven primarily by DMTs. There was a more than ninefold reduction in the neutralizing antibody (nAb) response among 13 patients on B-cell depleting agents, compared with no therapy or other therapies (P < .001). Among of individuals on these agents, 61.5% had no detectable nAb.

The researchers also found an association between postvaccine NT50 values and when the vaccine was received compared with the last infusion of B-cell depleting agents. Every additional day since the previous infusion was associated with a 3.7% increase in NT50 value (P = .0032).

The average length of exposure to B-cell depleting agents was 24 months and the median was 25 months. There was no association between length of time on a B-cell depleting agent and NT50 values after vaccination (Spearman correlation 0.35, P = .24).

Subanalyses by sex and vaccine type revealed no differences in nAb levels.

The study did not look at T-cell responses after vaccination or the effect of T-cell depleting agents, and T cells likely still provide some protection, according to Dr. Gyang. “Even though the vaccine response may not be as robust as it would have been if they were not on the drug, there is still some degree of protection,” she said.
 

Some answers, more questions

The study is important, even though it was presented at the time that the COVID-19 Omicron variant surge was waning. “COVID still remains a major concern. Even though it seems to be on the wane at the moment, that doesn’t mean it will be on the wane next week,” said Mark Gudesblatt, MD, medical director at South Shore Neurologic Associates (Patchogue, N.Y.), who was asked to comment on the study.

He noted that about 21% of patients in the study who received a vaccination had no detectable antibodies. “That’s a problem. You need to pick a medication that works, but not if the medication puts you at risk for other problems, especially in the world of now, where we know there are viral pandemics that occur. And that calls into question: What if you’re immunocompromised and you get a flu vaccine or a tetanus vaccine? How much do we know about the vaccination response to most of these? No one really considers [vaccine response] when choosing a medication,” said Dr. Gudesblatt.

The results broadly confirm what has been seen in other studies, though its focus on the humoral response is a limitation, according to Patricia Coyle, MD, professor of neurology and director of Stony Brook (N.Y.) MS Comprehensive Care Center. “For example, there have been independent studies with the (anti-CD-20 therapies) that indicate that they have a normal cell-mediated vaccine response to the COVID vaccine, even though the antibody response may be impaired in a significant number of individuals, though as you continue to vaccinate the antibody response seems to get better,” Dr. Coyle said in an interview.

Dr. Gyang has served as consultant for Genentech, Horizon Therapeutics, Greenwich Biosciences and EMD Serono. Dr. Gudesblatt has no relevant financial disclosures. Dr. Coyle has consulted or received speaker fees from Accordant, Alexion, Biogen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mylan, Novartis, Sanofi Genzyme, TG Therapeutics, and Viela Bio. Dr. Coyle has received research funding from Actelion, Alkermes, Celgene, CorEvitas LLC, Genentech/Roche, MedDay, Novartis, and Sanofi Genzyme.

Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.

Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.

Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.

The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.

Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.

“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.

The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.

Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.

Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.

Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.

The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.

Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.

“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.

The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.

Aspirin use failed to reduce recurrence rates among women with breast cancer in a phase 3, randomized, controlled trial that was halted following a planned futility analysis. The aspirin group actually had greater risk of recurrence, though the result did not reach statistical significance. Aspirin has proven effective in reducing recurrence rates in colon cancer.

Despite the disappointment of the results, Wendy Chen, MD, of Dana-Farber Cancer Institute, Boston, emphasized the value of the study. “Negative studies provide important data. You don’t want people doing something that’s not going to be helping them. There have been a lot of negative studies that have still provided important clinical information,” said Dr. Chen, who presented the results of the study at the ASCO Plenary Series.

Even study participants took the news with equanimity. “What has really been gratifying is that the patients, when we did tell them about the results, all of them [said] ‘I’m really glad I participated in the study anyway. I think it was an important question.’ And this is why we do studies. You don’t do studies because every single one of them is going to show a benefit. We do studies knowing that some of them are going to show no benefit,” said Dr. Chen.

The study included 3,021 women under age 70, recruited from 338 sites between 2017 and 2020, who were randomized to 300 mg daily aspirin or placebo. The median follow-up was 24.0 months. Dropout was high, with only 56% of patients still taking aspirin or placebo at the end of the study. The percentage was nearly identical in both arms. That low treatment rate could potentially explain the lack of an apparent effect, but Dr. Chen noted that the incidence of recurrence was actually higher in the aspirin group (hazard ratio, 1.25), though the result was not statistically significant (P = .1258). “The amount that it would need to flip in the second half [of the study] would really be of such a large magnitude to flip it. That biologically would not be plausible,” Dr. Chen said.

Previous epidemiological and even post hoc analyses of other clinical trials had suggested that aspirin might be effective at reducing recurrence in breast cancer, including data from 39,876 participants in the Women’s Health Study suggesting a reduction in risk of metastatic adenocarcinoma, but this isn’t the first time such evidence has led researchers and physicians astray. Dr. Chen pointed to hormone replacement therapy, which was prescribed for the prevention of breast cancer recurrence on the basis of similar evidence, but was shown to be harmful in a randomized, controlled trial.

“It was a very similar situation. Fortunately, the aspirin in this population was not causing harm, but it is possible that there are a lot of people who are just taking aspirin on their own, and they may be over 70, or they may have have other risk factors for adverse events that are different from our population,” Dr. Chen said.

The study was funded by the U.S. Department of Defense and the National Cancer Institute. Bayer provided aspirin and placebo for the study.

Chocolate: Now part of a well-balanced diet

Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.

Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?

Sascha Luehr/Pixabay

That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!

Oh, not that kind of roasting. Oops.

For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.

The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
 

The villain hiding in dairy for some MS patients

For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.

fcafotodigital/Getty Images

Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.

The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.

“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.

While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.

Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.

A small price to pay, perhaps, to stop a villainous evil twin.
 

You would even say it glows

If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?

Vnukko/Pixabay

Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.

It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”

People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”

Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.

It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
 

This is why you don’t interrupt someone using headphones

There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.

Weedezign/Thinkstock

According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.

“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.

These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.

We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.

Chocolate: Now part of a well-balanced diet

Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.

Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?

Sascha Luehr/Pixabay

That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!

Oh, not that kind of roasting. Oops.

For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.

The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
 

The villain hiding in dairy for some MS patients

For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.

fcafotodigital/Getty Images

Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.

The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.

“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.

While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.

Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.

A small price to pay, perhaps, to stop a villainous evil twin.
 

You would even say it glows

If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?

Vnukko/Pixabay

Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.

It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”

People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”

Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.

It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
 

This is why you don’t interrupt someone using headphones

There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.

Weedezign/Thinkstock

According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.

“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.

These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.

We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.

Chocolate: Now part of a well-balanced diet

Asking if someone loves chocolate is like asking if they love breathing. It’s really not a question that needs to be asked. The thing with chocolate, however, is that most people who love chocolate actually love sugar, since your typical milk chocolate contains only about 30% cacao. The rest, of course, is sugar.

Now, dark chocolate is actually kind of good for you since it contains beneficial flavonoids and less sugar. But that healthiness comes at a cost: Dark chocolate is quite bitter, and gets more so as the cacao content rises, to the point where 100% cacao chocolate is very nearly inedible. That’s the chocolate conundrum, the healthier it is, the worse it tastes. But what if there’s another way? What if you can have tasty chocolate that’s good for you?

Sascha Luehr/Pixabay

That’s the question a group of researchers from Penn State University dared to ask. The secret, they discovered, is to subject the cacao beans to extra-intense roasting. We’re not sure how screaming insults at a bunch of beans will help, but if science says so ... YOU USELESS LUMP OF BARELY EDIBLE FOOD! HOW DARE YOU EXIST!

Oh, not that kind of roasting. Oops.

For their study, the researchers made 27 unsweetened chocolates, prepared using various cacao bean roasting times and temperatures, and served them to volunteers. Those volunteers reported that chocolates made with cacao beans roasted more intensely (such as 20 minutes at 340° F, 80 min at 275° F, and 54 min at 304° F) were far more acceptable than were chocolates prepared with raw or lightly roasted cacao beans.

The implications of healthy yet tasty chocolate are obvious: Master the chocolate and you’ll make millions. Imagine a future where parents say to their kids: “Don’t forget to eat your chocolate.” So, we’re off to do some cooking. Don’t want Hershey to make all the money off of this revelation.
 

The villain hiding in dairy for some MS patients

For some of us, lactose can be a real heartbreaker when it comes to dairy consumption, but for people with multiple sclerosis (MS) there’s another villain they may also have to face that can make their symptoms worse.

fcafotodigital/Getty Images

Physicians at the Institute of Anatomy at University Hospital Bonn (Germany) were getting so many complaints from patients with MS about how much worse they felt about after having cheese, yogurt, and milk that they decided to get to the bottom of it. The culprit, it seems, is casein, a protein specifically found in cow’s milk.

The researchers injected mice with various proteins found in cow’s milk and found perforated myelin sheaths in those given casein. In MS, the patient’s own immune system destroys that sheath, which leads to paresthesia, vision problems, and movement disorders.

“The body’s defenses actually attack the casein, but in the process they also destroy proteins involved in the formation of myelin, “ said Rittika Chunder, a postdoctoral fellow at the University of Bonn. How? Apparently it’s all a big misunderstanding.

While looking at molecules needed for myelin production, the researchers came across MAG, which is very similar to casein, which is a problem when patients with MS are allergic to casein. After they have dairy products, the B-cell squad gets called in to clean up the evil twin, casein, but can’t differentiate it from the good twin, MAG, so it all gets a wash and the myelin sheath suffers.

Since this happens only to patients with MS who have a casein allergy, the researchers advise them to stay away from milk, yogurt, or cottage cheese while they work on a self-test to check if patients carry the antibodies.

A small price to pay, perhaps, to stop a villainous evil twin.
 

You would even say it glows

If you’re anything like us – and we think you are since you’re reading this – you’ve been asking yourself: Are there any common medications in my house that will make good radiation sensors?

Vnukko/Pixabay

Not that anyone needs to worry about excess radiation or anything. Far from it. We were just wondering.

It just so happens that Anna Mrozik and Paweł Bilski, both of the Institute of Nuclear Physics Polish Academy of Sciences (IFJ PAN) in Kraków, Poland, were wondering the same thing: “During an uncontrolled release of radiation, it is highly unlikely that members of the public will be equipped with personal radiation dose monitors.”

People would need to use something they had lying around the house. A smartphone would work, the investigators explained in a statement from the IFJ PAN, but the process of converting one to radiation-sensor duty, which involves dismantling it and breaking the display glass, “is laborious and time-consuming [and] the destruction of a valuable and useful device does not seem to be the optimal solution.”

Naturally, they turned to drugs. The key, in this case, is optically stimulated luminescence. They needed to find materials that would glow with greater intensity as the radiation dose increased. Turns out that ibuprofen- and paracetamol-based painkillers fit the bill quite nicely, although aspirin also works.

It’s not known exactly which substance is causing the luminescence, but rest assured, the “physicists from the IFJ PAN intend to identify it.”
 

This is why you don’t interrupt someone using headphones

There’s nothing like taking a nice relaxing walk with your headphones. Whether you’re listening to a podcast or a song or talking on the phone, it’s an escape from reality that makes you feel like you’re completely in tune with what you’re listening to.

Weedezign/Thinkstock

According to a new study, headphones, as opposed to speakers, make people feel more connected to what they are listening to. Data collected from more than 4,000 people showed that listening with headphones makes more of an impact than listening to speakers.

“Headphones produce a phenomenon called in-head localization, which makes the speaker sound as if they’re inside your head,” study coauthor On Amir of the University of California, San Diego, said in a statement. Because of this, people feel like the speakers are close to them and there’s more of a sense of empathy for the speakers and the listener is more likely to be swayed toward the ideas of the speaker.

These findings could lead to more efficient training programs, online work, and advertising, the investigators suggested.

We now finally understand why people get so mad when they have to take out their headphones to answer or talk to us. We ruined a satisfying moment going on in their brains.

The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.

Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.

After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium

“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.

Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.

However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.

The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
 

A ‘very valuable’ option

Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.

Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”

Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.

The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.

Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.

Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.

At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.

Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).

There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.

The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.

Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.

The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.

There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.

This article was updated on 3/10/22.

The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.

Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.

After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium

“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.

Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.

However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.

The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
 

A ‘very valuable’ option

Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.

Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”

Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.

The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.

Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.

Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.

At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.

Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).

There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.

The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.

Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.

The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.

There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.

This article was updated on 3/10/22.

The results of a large, matched cohort study from three major institutions have led investigators to call for broader use of trimodal therapy for muscle-invasive bladder cancer.

Radical cystectomy (RC), or the surgical removal of the whole bladder, prostate glands and seminal vesicles in men, or the bladder, uterus and fallopian tubes in women, is the traditional gold standard. But with trimodal therapy (TMT), patients can keep their bladders and avoid a long surgery. The procedure, which is called transurethral tumor resection, requires removing cancerous tumors from the bladder followed by chemoradiation.

After matching hundreds of patients requiring RC or TMT, “the oncologic outcomes seem to be equivalent. ...We do believe that TMT should be offered as an effective alternative for these patients,” said lead investigator Alexandre Zlotta, MD, PhD, director of uro-oncology at Mount Sinai Hospital, Toronto, after he presented the findings at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium

“The findings that patients with clinical T2 disease have similar outcomes with either approach is encouraging,” said Matthew Zibelman, MD,, an assistant hematology/oncology professor at Fox Chase Cancer Center, Philadelphia, when asked for comment.

Trimodal therapy is already an alternative to cystectomy in guidelines for patients with clinical T2-T3 disease who have no, or minor, unilateral hydronephrosis, and unifocal tumors of 7 cm or less, among other criteria.

However, oncologists shy away from it preferring to reserve trimodal therapy mostly for patients who are not candidates for surgery, Dr. Zlotta explained.

The problem is a lack of head-to-head randomized data comparing the two approaches. Attempts at trials in the past closed early because of lack of accrual, and it seems unlikely there’ll be another attempt in the future.
 

A ‘very valuable’ option

Dr. Zlotta and associates wanted to address the evidence gap with the next best thing, a large, matched cohort study. In lieu of a level 1 data, he said their work provides “the best possible evidence” comparing the two approaches and supports TMT as a “very valuable” option so long as centers can provide the necessary follow-up, including salvage cystectomy if needed.

Dr. Zibelman said the retrospective study “cannot completely account for unmeasured variables that may have predisposed patients to get trimodal therapy over surgery, which may have influenced the final data.”

Sill, “trimodal therapy likely provides oncologic outcomes similar to surgery in carefully selected patients ... and should be discussed ... as a bladder-preserving option,” he said.

The study matched 1 to 3, 282 patients undergoing trimodal therapy with 421 patients undergoing radical cystectomy. The patients were treated during 2005-2017 at Massachusetts General Hospital, Boston; the University of California, Los Angeles; or the Princess Margaret Cancer Centre, Toronto.

Patients had cT2-T3/4a disease without positive nodes or metastases. The entire cohort would have been eligible for either TMT or RC under current guidelines.

Propensity score matching produced well-balanced study arms, with a median age of about 71 years; cT2 disease in about 90%; hydronephrosis in about 11%, and adjuvant or neoadjuvant chemotherapy in about 60% of both arms.

At 5 years, both cancer-specific survival (78% with RC and 85% with TMT; P = .02) and overall survival favored TMT (66% RC vs. 78% TMT; P < .001), although Dr. Zlotta said the stark OS difference could have resulted from chance.

Trends also favored TMT in the primary outcome – 5-year metastasis free survival (73% RC vs. 78% TMT; P = .07) – as well as in distant failure-free survival (78% RC vs. 82% TMT; P = .14). The 5-year pelvic node failure-free survival was 96% in the RC group versus 94% with TMT (P = .33).

There were slight differences in surgical protocols between the study centers, and while adjuvant therapy was used at Massachusetts General, neoadjuvant chemotherapy was used in Toronto.

The differences might have introduced confounders, but “I have to say we were pretty reassured to see that we observed exactly the same results” regardless of where subjects were treated. It was “incredibly surprising, but comforting,” Dr. Zlotta said.

Another potential confounder – poor surgical technique – also wasn’t an issue. A median of 40 lymph nodes were removed during cystectomy, which “speaks to the quality of the surgical series,” he said.

The tumor recurrence rate was 20.5% in the TMT arm; 13% of patients had subsequent salvage cystectomies. Perioperative mortality was 2.1% in the RC arm.

There was no outside funding for the work. Dr. Zlotta had ties to numerous companies and honoraria/research funding from or being a consultant to AstraZeneca, Merck, Verity Pharmaceuticals, and others. Dr. Zibelman didn’t have any disclosures.

This article was updated on 3/10/22.

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Strong new evidence on the need to use an appropriately sized cuff in blood pressure measurement has come from the cross-sectional randomized trial Cuff(SZ).

The study found that in people in whom a small adult cuff was appropriate, systolic BP readings were on average 3.6 mm Hg lower when a regular adult size cuff was used.

However, systolic readings were on average 4.8 mm Hg higher when a regular cuff was used in people who required a large adult cuff and 19.5 mm Hg higher in those needing an extra-large cuff based on their mid-arm circumference.

The diastolic readings followed a similar pattern (-1.3 mm Hg, 1.8 mm Hg, and 7.4 mm Hg, respectively).

“We found that using the regular adult cuff in all individuals had striking differences in blood pressure,” lead author Tammy M. Brady, MD, PhD, Johns Hopkins University School of Medicine, Baltimore, told this news organization. “And that has a lot of clinical implications.”

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

Incidence rates for testicular cancer have been rising in the United States, as have related mortality rates, but there are wide variations by race/ethnicity and geographic location, a new analysis shows.

Testicular cancer is the most common type of malignancy in young men between the ages of 20 and 34 years, although overall, it is relatively uncommon and represents only 0.5% of all new cancer cases in the U.S.

The new analysis shows that age-adjusted testicular cancer–specific mortality rates in the United States increased from 1999-2019, particularly among Hispanic men. During the same period, mortality rates declined somewhat among Black men as compared to White men.

“Given that testicular cancer generally has a favorable prognosis, it is concerning that mortality rates for this disease are increasing,” said lead author Anushka Ghosh, BS, a clinical research coordinator at Massachusetts General Hospital, Boston. “It is crucial to understand these trends and make targeted efforts to address any geographic, racial, and ethnic gaps in testicular cancer care.”

She presented the findings at the Genitourinary Cancers Symposium (GUCS) 2022.

“Testicular cancer is a rare but very curable disease,” said Daniel Geynisman, MD, associate professor in the Department of Hematology/Oncology at Fox Chase Cancer Center, Philadelphia, who was approached for comment. “The increase in testicular cancer deaths for Hispanic men is concerning.”

“Whether this change relates to suboptimal access to appropriate care or change in biology as a result of socioeconomic or geographic changes in Hispanic men over the recent years is unknown but needs to be urgently explored and addressed,” he added.
 

Details of the new findings

For their analysis, Ms. Ghosh and colleagues assessed recent changes in testicular cancer mortality rates over time in the United States with respect to race, ethnicity, and geography. They used the Centers for Disease Control’s Wide-Ranging Online Data for Epidemiologic Research database to obtain the number of age-adjusted death rates for individuals across all U.S. counties over a 21-year period (1999-2019).

During this period, overall age-adjusted testicular cancer mortality rates rose slowly but not significantly, with an overall increase of 0.0002 per 100,000 population per year. This increase was significantly worse among Hispanic men, among whom the increase was 0.0019 per 100,000, compared with a 0.0003 per 100,000 decrease among non-Hispanic men (comparison P = .010).

But when stratified by race (Black vs. White), the authors saw that Black men had somewhat improved rates. Among Black men, the rate decreased by 0.0007 per 100,000, compared with an increase of 0.0006 per 100,000 among White men, a difference that reached statistical significance (P = .049).

“We also observed significant geographical differences in mortality rates,” said Ms. Ghosh.

They divided the U.S. into four regions: the Northeast, the Midwest, the South, and the West. There were no differences in the South and the Midwest, but mortality rates decreased in the Northeast by 0.00092 per 100,000 and rose in the West by 0.00086 per 100,000 (P for difference between slopes = .032).

The authors also looked at differences in urbanization categories or population density and found that large central metro regions (central counties in metro areas with population greater than 1 million) and small metro regions (counties with population 50,000-249,999) were significantly different. While testicular cancer mortality rates decreased slightly in large central metropolitan regions by 0.0004, rates increased slightly in small metropolitan regions (0.0022; P for difference = .048). No other significant differences based on urbanization were noted.

Also approached for comment, Matt D. Galsky, MD, director of genitourinary medical oncology at the Tisch Cancer Institute at Mount Sinai, noted that the finding that testicular cancer mortality rates increased from 1999-2019 was not statistically significant.

However, there were significant trends among subgroups. Testicular cancer mortality increased during this period among Hispanic men, he pointed out. “Importantly, while statistically significant, the differences are numerically small. That said, testicular cancer is a generally a highly curable malignancy, so any disparities related to mortality may be notable and worth further investigation.

“There are several potential underlying causes of such disparities, some of which could be probed with additional clinical details, and some of which might involve a more complex interplay of access and tumor biology,” he continued. “For example, testicular cancers are broadly separated into two subtypes: seminoma and nonseminoma. Whether the trends in these two subtypes in Hispanic men are different compared to non-Hispanic men could be one clue into the observed disparities.”

Ms. Ghosh, Dr. Geynisman, and Dr. Galsky have disclosed no relevant financial relationships.

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

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

In patients with persistent atopic dermatitis (AD) who are taking dupilumab, is there benefit of patch testing to determine if allergic contact dermatitis (ACD) also is contributing to their disease? Results of patch testing are likely be influenced by the immunomodulatory effects of dupilumab. Similar to the recommendation for patients to refrain from using topical or systemic corticosteroids for 1 week or more prior to patch testing to eliminate false negatives, we reviewed the literature to create practice guidelines for dermatologists regarding patch testing while a patient is taking dupilumab.

Pathophysiology and Pathomechanism

Dupilumab functions through the blockade of T helper 2 (T_H2) cells; ACD is propagated through the T helper 1 (T_H1) cellular pathway. However, patients with ACD that is unresponsive to allergen avoidance and traditional therapies, such as topical and oral corticosteroids, have responded to dupilumab. The more common reports of this responsiveness are with fragrances; multiple case series described patients with ACD to fragrance mix I¹ and balsam of Peru^1,2 who improved on dupilumab when other treatments failed. There also are reports of response when ACD was secondary to nickel,^2,3p-phenylenediamine,¹ Compositae,⁴ and non–formaldehyde-releasing preservatives (non-FRPs).⁵ Therefore, not all ACD is propagated through the T_H1 cellular pathway.

As noted in these cases, ACD can be a response to an allergen whose pathogenesis involves the T_H2 pathway or when patient characteristics favor a T_H2 response. It has been suggested that AD patients are more susceptible to T_H2-mediated contact sensitization to less-potent allergens, such as fragrances.⁶

Patch Test Results

Positive patch test results for allergens have been reported while patients are on dupilumab therapy, including a few studies in which results prior to starting dupilumab were compared with those while patients were on dupilumab therapy. In a retrospective chart review of 48 patients on dupilumab for AD with persistent disease, 23 patients were patch tested before and during dupilumab therapy. In these patients, the majority of contact allergies were persistent and only 10% (13/125) of patch test–positive results resolved on dupilumab therapy.⁷ Contact allergies that resolved included those to emulsifiers (propylene glycol, Amerchol L101 [lanolin-containing products found in cosmetics and other goods], dimethylaminopropylamine), fragrances (fragrance mix I, balsam of Peru), sunscreens (sulisobenzone, phenylbenzimidazole-5-sulfonic acid), and metals (vanadium chloride, phenylmercuric acetate).⁷ The following results observed in individual cases demonstrated conflicting findings: persistence of allergy to non-FRPs (methylisothiazolinone [MI]) but resolution of allergy to formaldehyde⁸; persistence of allergy to corticosteroids (budesonide and alclometasone)⁹; persistence of allergy to an antibiotic (neomycin sulfate) but resolution of allergies to a different antibiotic (bacitracin), glues (ethyl acrylate), bleach, and glutaraldehyde⁹; persistence of nickel allergy but resolution of allergies to fragrances (cinnamic aldehyde, balsam of Peru) and non-FRPs (methylchloroisothiazolinone or MI)¹⁰; and persistence of allergies to non-FRPs (MI) and FRPs (bronopol) but resolution of allergies to nickel, fragrances (hydroperoxides of linalool), and Compositae.¹¹ Additional case reports of positive patch test results while on dupilumab but with no pretreatment results for comparison include allergies to rubber additives,^12-14 nickel,¹⁴ textile dyes,¹⁴ cosmetic and hair care additives,^12,14,15 corticosteroids,¹⁵ FRPs,¹⁵ fragrances,^15,16 emulsifiers,¹⁶ and non-FRPs.¹⁷

An evident theme in the dupilumab patch-testing literature has been that results are variable and case specific: a given patient with ACD to an allergen will respond to dupilumab treatment and have subsequent negative patch testing, while another patient will not respond to dupilumab treatment and have persistent positive patch testing. This is likely because, in certain individuals, the allergen-immune system combination shifts ACD pathogenesis from a purely T_H1 response to at least a partial T_H2 response, thus allowing for benefit from dupilumab therapy. T helper 1 cell–mediated ACD should not be affected by dupilumab; therefore, reliable results can be elucidated from patch testing despite the drug.

Final Thoughts

We propose that AD patients with residual disease after taking dupilumab undergo patch testing. Positive results indicate allergens that are not inhibited by the drug. Patients will need to follow strict allergen avoidance to resolve this component of their disease; failure to improve might suggest the result was a nonrelevant positive.

If patch testing is negative, an alternative cause for residual disease must be sought. We do not recommend stopping dupilumab prior to patch testing to avoid a disease flare from AD or possible T_H2-mediated ACD.

Practice Gap

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus are US Food and Drug Administration approved for the treatment of atopic dermatitis.¹ In addition, these 2 drugs are utilized off label for many other dermatologic conditions, including vitiligo, psoriasis, and periorificial dermatitis. They can be used safely for prolonged periods and on sensitive areas, including the face.

Treatment with a TCI provides advantages over topical steroids, which can cause atrophy, telangiectasia, dyspigmentation, ocular hypertension, cataracts, and tachyphylaxis after prolonged use. Adverse events resulting from use of a TCI most commonly include transient burning, warmth, and erythema in areas of application. Patients typically acclimate to these effects after a few consecutive days of use.

Localized flushing after alcohol ingestion is a known potential side effect of TCIs¹; however, this association may be underappreciated and underreported to patients.

Counseling Patients Taking TCIs

Topical calcineurin inhibitors cause alcohol-induced flushing on areas of application (Figures 1 and 2) in approximately 3.4% to 6.9% of patients.¹ The reaction has been reported with both topical TCIs but more often is noted with tacrolimus.^2,3 Typically, flushing begins 2 to 4 weeks after treatment is initiated and within 5 to 20 minutes after alcohol intake.⁴ The phenomenon is self-limited; erythema typically resolves in 20 to 60 minutes.

Topical calcineurin inhibitors are hypothesized to cause alcohol-induced flushing by locally inhibiting acetaldehyde dehydrogenase, an enzyme necessary for alcohol metabolism. This leads to accumulation of acetaldehyde, a by-product of alcohol metabolism, which indirectly causes concentrated vasodilation by means of prostaglandins, histamines, and other vasodilatory mediators. The combination of ethanol and a TCI also might induce release of neuropeptides, which could cause vasodilation.⁴

Alcohol-related flushing commonly is seen among individuals who are aldehyde dehydrogenase 2 (ALDH2) deficient; it is sometimes accompanied by nausea, headache, and tachycardia. The same pathway is implicated in disulfiram reactions, to a more intense and systemic degree, to discourage alcohol intake.

Oral calcineurin inhibitors are not reported to cause generalized flushing, perhaps because of differences in the relative dose. For example, topical tacrolimus 0.1% is 1 mg/g that is applied to a relatively small body surface area; oral calcineurin inhibitors are dosed at a range of 1 to 15 mg for an entire person.

Techniques to Avoid Flushing

Discontinuing a TCI altogether leads to resolution of associated adverse effects, including flushing, typically within weeks to 1 month.⁵ Alternatively, oral aspirin (81 mg) might eliminate or attenuate symptoms, as documented in a double-blind, controlled trial in which relief of TCI-induced flushing after consuming wine was investigated.⁶

Another approach (albeit nontraditional) is for patients who experience this phenomenon to “wet their whistles” with an alcoholic drink before a social engagement. After flushing resolves in 20 to 60 minutes, subsequent drinks do not appear to elicit symptoms again in most patients. That said, we stop short of calling this tip “doctor’s orders.”

Practical Implication

Counseling patients who will be using a TCI—tacrolimus or pimecrolimus—about the potential for these drugs to produce localized flushing after alcohol ingestion as well as techniques for lessening or eliminating this adverse effect are important facets of their dermatologic care.

Practice Gap

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus are US Food and Drug Administration approved for the treatment of atopic dermatitis.¹ In addition, these 2 drugs are utilized off label for many other dermatologic conditions, including vitiligo, psoriasis, and periorificial dermatitis. They can be used safely for prolonged periods and on sensitive areas, including the face.

Treatment with a TCI provides advantages over topical steroids, which can cause atrophy, telangiectasia, dyspigmentation, ocular hypertension, cataracts, and tachyphylaxis after prolonged use. Adverse events resulting from use of a TCI most commonly include transient burning, warmth, and erythema in areas of application. Patients typically acclimate to these effects after a few consecutive days of use.

Localized flushing after alcohol ingestion is a known potential side effect of TCIs¹; however, this association may be underappreciated and underreported to patients.

Counseling Patients Taking TCIs

Topical calcineurin inhibitors cause alcohol-induced flushing on areas of application (Figures 1 and 2) in approximately 3.4% to 6.9% of patients.¹ The reaction has been reported with both topical TCIs but more often is noted with tacrolimus.^2,3 Typically, flushing begins 2 to 4 weeks after treatment is initiated and within 5 to 20 minutes after alcohol intake.⁴ The phenomenon is self-limited; erythema typically resolves in 20 to 60 minutes.

Topical calcineurin inhibitors are hypothesized to cause alcohol-induced flushing by locally inhibiting acetaldehyde dehydrogenase, an enzyme necessary for alcohol metabolism. This leads to accumulation of acetaldehyde, a by-product of alcohol metabolism, which indirectly causes concentrated vasodilation by means of prostaglandins, histamines, and other vasodilatory mediators. The combination of ethanol and a TCI also might induce release of neuropeptides, which could cause vasodilation.⁴

Alcohol-related flushing commonly is seen among individuals who are aldehyde dehydrogenase 2 (ALDH2) deficient; it is sometimes accompanied by nausea, headache, and tachycardia. The same pathway is implicated in disulfiram reactions, to a more intense and systemic degree, to discourage alcohol intake.

Oral calcineurin inhibitors are not reported to cause generalized flushing, perhaps because of differences in the relative dose. For example, topical tacrolimus 0.1% is 1 mg/g that is applied to a relatively small body surface area; oral calcineurin inhibitors are dosed at a range of 1 to 15 mg for an entire person.

Techniques to Avoid Flushing

Discontinuing a TCI altogether leads to resolution of associated adverse effects, including flushing, typically within weeks to 1 month.⁵ Alternatively, oral aspirin (81 mg) might eliminate or attenuate symptoms, as documented in a double-blind, controlled trial in which relief of TCI-induced flushing after consuming wine was investigated.⁶

Another approach (albeit nontraditional) is for patients who experience this phenomenon to “wet their whistles” with an alcoholic drink before a social engagement. After flushing resolves in 20 to 60 minutes, subsequent drinks do not appear to elicit symptoms again in most patients. That said, we stop short of calling this tip “doctor’s orders.”

Practical Implication

Counseling patients who will be using a TCI—tacrolimus or pimecrolimus—about the potential for these drugs to produce localized flushing after alcohol ingestion as well as techniques for lessening or eliminating this adverse effect are important facets of their dermatologic care.

Practice Gap

The topical calcineurin inhibitors (TCIs) tacrolimus and pimecrolimus are US Food and Drug Administration approved for the treatment of atopic dermatitis.¹ In addition, these 2 drugs are utilized off label for many other dermatologic conditions, including vitiligo, psoriasis, and periorificial dermatitis. They can be used safely for prolonged periods and on sensitive areas, including the face.

Treatment with a TCI provides advantages over topical steroids, which can cause atrophy, telangiectasia, dyspigmentation, ocular hypertension, cataracts, and tachyphylaxis after prolonged use. Adverse events resulting from use of a TCI most commonly include transient burning, warmth, and erythema in areas of application. Patients typically acclimate to these effects after a few consecutive days of use.

Localized flushing after alcohol ingestion is a known potential side effect of TCIs¹; however, this association may be underappreciated and underreported to patients.

Counseling Patients Taking TCIs

Topical calcineurin inhibitors cause alcohol-induced flushing on areas of application (Figures 1 and 2) in approximately 3.4% to 6.9% of patients.¹ The reaction has been reported with both topical TCIs but more often is noted with tacrolimus.^2,3 Typically, flushing begins 2 to 4 weeks after treatment is initiated and within 5 to 20 minutes after alcohol intake.⁴ The phenomenon is self-limited; erythema typically resolves in 20 to 60 minutes.

Topical calcineurin inhibitors are hypothesized to cause alcohol-induced flushing by locally inhibiting acetaldehyde dehydrogenase, an enzyme necessary for alcohol metabolism. This leads to accumulation of acetaldehyde, a by-product of alcohol metabolism, which indirectly causes concentrated vasodilation by means of prostaglandins, histamines, and other vasodilatory mediators. The combination of ethanol and a TCI also might induce release of neuropeptides, which could cause vasodilation.⁴

Alcohol-related flushing commonly is seen among individuals who are aldehyde dehydrogenase 2 (ALDH2) deficient; it is sometimes accompanied by nausea, headache, and tachycardia. The same pathway is implicated in disulfiram reactions, to a more intense and systemic degree, to discourage alcohol intake.

Oral calcineurin inhibitors are not reported to cause generalized flushing, perhaps because of differences in the relative dose. For example, topical tacrolimus 0.1% is 1 mg/g that is applied to a relatively small body surface area; oral calcineurin inhibitors are dosed at a range of 1 to 15 mg for an entire person.

Techniques to Avoid Flushing

Discontinuing a TCI altogether leads to resolution of associated adverse effects, including flushing, typically within weeks to 1 month.⁵ Alternatively, oral aspirin (81 mg) might eliminate or attenuate symptoms, as documented in a double-blind, controlled trial in which relief of TCI-induced flushing after consuming wine was investigated.⁶

Another approach (albeit nontraditional) is for patients who experience this phenomenon to “wet their whistles” with an alcoholic drink before a social engagement. After flushing resolves in 20 to 60 minutes, subsequent drinks do not appear to elicit symptoms again in most patients. That said, we stop short of calling this tip “doctor’s orders.”

Practical Implication

Counseling patients who will be using a TCI—tacrolimus or pimecrolimus—about the potential for these drugs to produce localized flushing after alcohol ingestion as well as techniques for lessening or eliminating this adverse effect are important facets of their dermatologic care.