Conference Coverage

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

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

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

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

CHARLOTTE, N.C. – People with moderate to severe ulcerative colitis benefit from stronger treatment from the start – a combination of monoclonal antibodies – compared with induction with either agent alone, a phase 2a study demonstrates.

Researchers compared the combination therapy of guselkumab and golimumab (both from Janssen) for 12 weeks, followed by guselkumab monotherapy up to week 38, versus either agent as monotherapy for the full 38 weeks.

Guselkumab is an interleukin-23p19 subunit antagonist being studied to treat inflammatory bowel disease (IBD). Golimumab is a TNF-alpha antagonist being evaluated for ulcerative colitis.

University of Western Ontario, London

The combination induction strategy “achieved higher rates of clinical remission, endoscopic improvement, composite endpoint of histologic remission, and endoscopic improvement,” said Brian G. Feagan, MD, senior scientific director at the contract research organization Alimentiv and a gastroenterologist at Western University in London, Ont.

The findings were presented at the annual meeting of the American College of Gastroenterology.
 

Study design

The current research builds on previous week 12 VEGA study results. The earlier findings indicated that blocking interleukin-23p19 by guselkumab and TNF-alpha with golimumab was superior on multiple measures, compared with monotherapy.

The new findings are from a randomized, double-blind, proof-of-concept study that included 214 adults with moderately to severely active ulcerative colitis. Participants were naive to TNF-alpha antagonists and refractory or intolerant to conventional therapy.

Of the participants, 71 were randomly assigned to receive guselkumab, 200 mg intravenous (IV) at baseline and at weeks 4 and 8, plus 100 mg subcutaneous (SC) every 8 weeks.

Another 72 participants received golimumab, 200 mg SC at baseline, and 100 mg SC at weeks 2, 6, and 10, and every 4 weeks thereafter.

The combination group of 71 participants received guselkumab 200 mg IV and golimumab 200 mg SC at baseline, followed by golimumab 100 mg SC at weeks 2, 6, and 10, and guselkumab 200 mg IV at weeks 4 and 8. At week 12, this group switched to monotherapy with guselkumab, 100 mg SC every 8 weeks.

Overall, 13% of patients discontinued treatment prior to week 34, the time of final dose of study intervention.

Dr. Feagan noted that they did not see differences between any adverse event, serious adverse event, or adverse event leading to discontinuation among the treatment groups.
 

Key findings through week 38

The rate of clinical remission in the combination group was 44%. The rate was lower with guselkumab monotherapy at 31% and golimumab monotherapy at 22% at week 38. These percentages were based on a full Mayo Score of 2 or less and no individual subscore greater than 1.

At the same time, the rates of clinical remission by modified Mayo score also favored the combination group at 48%, followed by 31% in the guselkumab group and 21% in the golimumab cohort.

Endoscopic improvement, endoscopic normalization, histologic remission, and composite histologic-endoscopic endpoints were also greater in the combination group than in the monotherapy groups.

“Quite striking differences were maintained up to week 38,” Dr. Feagan said. “This combination treatment warrants further investigation, and phase 3 trials are underway.”

He added that, while they were concerned about serious infection, they did not see any differences, with only two serious infections in each of the three groups.

Opportunistic infections were reported for two patients in the combination group: extrapulmonary tuberculosis and cytomegalovirus colitis. No opportunistic infections occurred in the monotherapy groups.
 

Valuable data

“The early study results, such as the VEGA study, appear promising for combination biologics with a good safety profile,” Jean-Paul Achkar, MD, staff physician in the Center for Inflammatory Bowel Disease at Cleveland Clinic and the Kenneth Rainin Endowed Chair for IBD Research, said when asked to comment.

“These data are particularly valuable as we have seemingly reached a therapeutic response ceiling for single-biologic therapy, and we need to determine the added benefit and safety profile of a combination of two biologics or the combination of a biologic and a small molecule,” added Dr. Achkar, who served as the session comoderator.

A meeting attendee asked about the likelihood of regulatory approval for this combination based on evidence like this study.

“I think they have to,” Dr. Feagan said. “We’ve probably seen our best results yet in Crohn’s disease, and we’re still at 50% [response rate for monotherapy]. If we’re ever going to come to terms with IBD, I don’t think it’s monotherapy.”

Dr. Feagan added that with combination therapy, “physicians will often worry about economics, but I think that’s a surrogate for their concerns about infection.”

However, he noted that “the better the agents we have, the better the incremental cost effectiveness. So, I don’t think economics is the issue; the issue is safety.”

Another meeting attendee asked if the results might apply to other biologic combinations.

“This model was picked to show the additive effect of the anti-p19 and the TNF antagonist,” Dr. Feagan said.

Similar results could be expected with a combination of treatments from the same classes, he said, but the treatment potential of other drug-class combination is unclear.

The study was funded by Janssen Research and Development. Dr. Feagan reports being a consultant for Janssen. Dr. Achkar reports no relevant financial relationships.

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

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

A new study provides more evidence that HPV infection doesn’t raise the risk of poor outcomes in women who undergo fertility treatment via in vitro fertilization with fresh embryos. In fact, HPV-positive women were somewhat more likely than HPV-negative women to become pregnant (relative risk, 1.20; 95% confidence interval, 1.03-1.39) and have live births (RR, 1.39; 95% CI, 1.13-1.70), researchers reported Oct. 24 at the American Society for Reproductive Medicine’s 2022 meeting .

“This evidence should reassure women that being HPV positive will not affect live birth rates after a fresh embryo transfer cycle,” said study coauthor and ob.gyn. Nina Vyas, MD, a clinical fellow at Weill Cornell Medicine, New York, in an interview.

According to Dr. Vyas, previous studies have offered conflicting results about whether HPV affects pregnancy outcomes. In 2006, for example, her group performed a pilot study (Fertil Steril. Jun 16. doi: 10.1016/j.fertnstert.2006.01.051) that linked lower pregnancy rates to HPV-positive tests on the day of egg retrieval.

“We sought to reevaluate this finding in a retrospective manner,” Dr. Vyas said. “You’re taking eggs out of their home, injecting with sperm, and putting them back. There’s so much that we don’t know, and we want to make sure there’s no extra risk.”

Also, she added, “prior studies had a relatively low sample size. We sought to use our patient volume to address this question on a larger scale. Our current study benefits from a large sample size and using the clinically meaningful endpoint of live birth as our primary outcome.”

For the new study, researchers retrospectively analyzed 1,333 patients (of 2,209 screened) who received first fresh embryo transfers from 2017 to 2019. All had cytology or HPV status documented per cervical cancer screening guidelines within 6 months before embryos were transferred.

The researchers looked at only fresh embryo transfers “so we could account for pregnancy outcomes closest to the documented HPV status at the time of egg retrieval,” Dr. Vyas said.

Ten percent (133) of patients were HPV positive. Of those, 60.1% became pregnant, and 43.6% of them had live births. Of the HPV-negative women (90% of subjects, n = 1,200), 52.2% became pregnant and 33.5% had live births. The researchers didn’t calculate P values, but Dr. Vyas said an analysis determined that the differences between HPV-positive and HPV-negative women were statistically significant.

The study size doesn’t allow researchers to determine whether HPV actually has a protective effect on pregnancy/live birth rates in IVF, Dr. Vyas said. Even if it did, the virus is dangerous.

What else could explain the discrepancy? “Some elements driving this could the smaller sample size of the HPV-positive group, differences in HPV prevalence between the general population and our population,” she said, “or other confounding factors we were not able to appreciate due to the limitations of the retrospective study.”

Researchers also reported that they found “no significant difference in biochemical or spontaneous abortion rates” between HPV-positive and HPV-negative women.

What is the message of the study? “Women with HPV can rest assured that they won’t have worse outcomes than their non-HPV [infected] counterparts after a fresh embryo transfer cycle,” Dr. Vyas said.

In an interview, McGill University, Montreal, epidemiologist Helen Trottier, PhD, MSc, noted that she recently coauthored a study that linked persistent HPV infection in pregnancy to premature births. The findings appear convincing, she said: “I think we can say that HPV is associated with preterm birth.”

She praised the new study but noted “the relative risks that are reported need to be adjusted for race and possibly other factors.”

Dr. Vyas said that kind of adjustment will occur in a future study that’s in progress. “We are now prospectively enrolling patients and collecting cytology data to understand whether there might be a difference for women with higher malignancy potential/different types of HPV genotypes.”

The study authors have no disclosures. Disclosure information for Dr. Trottier was unavailable.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

High-efficacy therapies for multiple sclerosis (MS) have improved disease outcomes for many patients, but physicians are uncertain when to use them. Despite better long-term disease outcomes, there are concerns over long-term safety, and some physicians and patients remain wary of these medications.

High-efficacy therapies were the subject of a session at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Key topics included patient selection, timing of escalation to high-efficacy therapies, and initial use of high-efficacy therapies. The session produced a compelling message, according to moderator Patricia Coyle, MD. “I think [the speakers provided] accumulating data that this is a smart thing to do: Use high-efficacy therapies early to get the maximum bang for the buck,” Dr. Coyle said in an interview. She is professor of neurology and director of the MS Comprehensive Care Center at Stony Brook (N.Y.) University.
 

Consider baseline characteristics

In the first talk, Xavier Montalban, MD, PhD, noted that a statement from the ECTRIMS/EAN (European Academy of Neurology) guideline update in 2021 said that a high-efficacy disease-modifying therapy (DMT) should be considered early in the disease course. A key question is whether any baseline characteristics can be used to select patients, and studies have shown worse prognosis with older age, male sex, low levels of vitamin D, and smoking status, among various other factors.

He presented subgroup analyses from trials of fingolimod and ozanimod, which showed that the drugs did not work as well in patients with poor prognostic factors such as an Expanded Disability Status Scale (EDSS) score of 4 or above and age over 40 years. Lower doses also tend to have less efficacy in males. “If you have [a patient with] bad baseline prognostic factors, you need high-efficacy medication at the right dose, because a lower dose will not work well. It is the same phenomenon for age,” Dr. Montalban said in his talk. On the other hand, he showed the results of a study of ofatumumab and ocrelizumab, both of which showed high efficacy even in patients with poor prognostic factors.

Among patients with secondary progressive MS, clinical or MRI evidence of inflammatory activity is the only poor prognostic factor that appears to be a good predictor of treatment response.

Dr. Montalban also addressed the timing of intervention with DMTs. A study from his group prospectively followed 1,015 patients treated with DMTs. “Interestingly, what we observed is that patients who were treated with DMTs just after the first attack did better than those who were treated after the second attack, and you have to take into consideration that we treat those patients after the first attack, those who had the worst prognostic factors, so treatment was very effective in that sense,” said Dr. Montalban, director of the Multiple Sclerosis Centre of Catalonia at Vall d’Hebron University Hospital in Barcelona.
 

Switching DMTs

In the second presentation, Dalia Rotstein, MD, discussed how to incorporate prognostic factors when switching a patient to high-efficacy therapies as a result of new disease activity while on another therapy.

Patients with favorable prognostic factors at baseline may be started out on immunomodulatory therapy. “Essentially, we want to match the intensity of the therapy to the intensity of the disease of the patient in front of us,” Dr. Rotstein said in her talk. Nevertheless, the course of MS is unpredictable, and the first year or two of immunomodulatory therapy can give physicians clues about the longer-term course of the disease. “We need to observe closely for disease activity in the first year, but even up to 2 years on therapy to determine a need for early escalation,” said Dr. Rotstein, assistant professor of medicine at University of Toronto.

For switching to high-efficacy therapies, any relapse, disability progression, or an EDSS change of 1 point or more could be a consideration. MRI indicators are more controversial, but one to three new T2 lesions also could prompt a switch.

Serum neural filament light chain (sNFL) is a useful biomarker for monitoring disease activity as it correlates well with new disease activity within the next year. It can be monitored every 3-4 months and adjusted for clinical factors and monitored for changing levels. A concerning finding can be followed up with an MRI or in-person visit.

When switching to a high-efficacy therapy, it’s important to administer any vaccines well in advance to ensure a good immune response.

When it comes to a washout period, physicians need to consider both the risk of immunosuppression and breakthrough disease activity. “But in general, we’ve observed that we can minimize the duration of the washout when stopping initial immunomodulator therapy to reduce the risk of breakthrough disease activity. We need to pay particular attention to the risk of rebound activity with longer washouts after stopping sphingosine-1 phosphate (S1P) receptor modulators because the rebound activity can be devastating,” said Dr. Rotstein.

A study of timing of relapses after fingolimod washout, carried out by Dr. Rotstein’s group, found a stark signal. “We observed that when the washout after fingolimod discontinuation was 30 days or more, there is a very high risk of early relapse,” she said.
 

The case for induction therapy

In the third talk, Gavin Giovannoni, MBBCh, PhD, discussed “flipping the pyramid” – that is, starting patients off immediately with high-efficacy therapies rather than waiting until they progress on other therapies. He likened such a decision to a gambler, because MS patients on less-effective therapy can suffer irreversible, long-term physical consequences, as well as social consequences such as unemployment due to cognitive effects.

“We always tend to put up a graph about the risks and benefits of a specific treatment, and we forget about the risks of untreated or undertreated MS. Keep that in mind when making decisions about high-efficacy therapies,” said Dr. Giovannoni, professor of neurology at Queen Mary University of London.

About 80% of patients on tier 1, or low-efficacy therapies, will have breakthrough activity on MRI within 4 years. Moving up a tier gets to about a 60% rate of breakthrough activity. High-efficacy therapies attain an efficacy of about 80% at 6 months. “If you have MS, you’ve got to realize that if you had to roll the dice, which tier would you want to be in? By putting all of them [on high-efficacy therapies], you’re going to get the majority responding and a few of them will break through,” said Dr. Giovannoni.

He presented some real-world evidence to back up the argument: A study comparing outcomes in Sweden and Denmark, which have similar demographics. In Denmark, 7.6% of patients with MS received high-efficacy therapies initially, while in Sweden the proportion was 34.5%. Patients with MS treated in Sweden had a 29% lower probability of progressing to disability (P = .004) and there were 22% fewer discontinuations of DMTs (P < .001). Since that study, the proportion of patients receiving high-efficacy therapies to begin with is closer to 70%. “This is compelling evidence that you want to be on a [high-efficacy therapy] early. If I had MS, I would want to live in Sweden,” said Dr. Giovannoni.

Historical treatments focused on reducing relapses, and more recently on eliminating evidence of inflammatory disease. He said that physicians are prioritizing brain volume loss to improve long-term outcomes in MS, and some are studying long-term disability. “We know that brain volume loss in MS is a prognostic sign both at baseline and at follow-up. It predicts poor outcome, poor cognition and employment, poor quality of life, et cetera,” said Dr. Giovannoni.

He cited data from studies of alemtuzumab that showed a significant reduction in brain volume loss. “The rate is about 0.2% per annum, which is kind of getting into the normal range for age-matched controls. Those people who were started off on interferons in the study lost a lot of brain volume in those first 2 years, and that’s irreversible,” said Dr. Giovannoni.

He pointed out that studies of hematopoietic stem cell therapy showed similar brain-volume outcomes. “So flipping the pyramid with the two most highly effective therapies almost normalizes brain volume loss in people with MS,” said Dr. Giovannoni.

There is also evidence in other autoimmune diseases that early use of high-efficacy therapies improves outcomes. More aggressive therapy in rheumatoid arthritis has reduced joint replacements by 90%.

“I think you really, really need to give your patients the opportunity of flipping the pyramid. You shouldn’t decide that for them,” said Dr. Giovannoni.

Dr. Coyle has consulted for nearly all pharmaceutical companies developing drugs in the MS space. Dr. Montalban has financial relationships with Biogen Idec, Merck Serono, Genentech, Genzyme, Novartis, Sanofi-Aventis, Teva, Roche, Celgene, Actelion, Mylan, BMS, and Sandoz. Dr. Rotstein has financial ties with Roche Canada, Alexion, Biogen, EMD Serono, Novartis, Roche, and Sanofi Aventis. Dr. Giovannoni has financial ties with AbbVie, Aslan, Atara Bio, Biogen, BMS-Celgene, GlaxoSmithKline, GW Pharma, Janssen/J&J, Japanese Tobacco, Jazz Pharmaceuticals, LifNano, Merck & Co., Merck KGaA/EMD Serono, Moderna, Novartis, Sanofi, Roche/Genentech, and Teva.

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

CINCINNATI – Sickle cell disease is well known for its associated anemia, but patients experience a range of other complications as well. These include vision and kidney problems, delayed growth, susceptibility to infection, and pain.

Another issue, not always as well recognized, is a considerably heightened risk for childhood stroke. “Children with sickle cell disease have 100 times the risk of stroke as other children without sickle cell disease, and there’s also an elevated risk of five times the general population in adults with sickle cell disease,” said Lori Jordan, MD, PhD, in an interview.

At the 2022 annual meeting of the Child Neurology Society, Dr. Jordan spoke about stroke as a complication of sickle cell disease, and the role that neurologists can play in preventing primary or secondary strokes. “At least in children, studies have shown that if we screen and identify patients who are at highest risk of stroke, there are primary prevention therapies – usually implemented by hematologists, but that neurologists often are involved with – both monitoring for cognitive effects of silent cerebral infarct and also with treating patients who unfortunately still have an acute stroke,” said Dr. Jordan, who is an associate professor of pediatrics, neurology, and radiology at Vanderbilt University Medical Center, Nashville, Tenn. She also is director of the pediatric stroke program at Vanderbilt.
 

Time is of the essence

“In general, stroke in children is rare, but it’s more common in sickle cell disease, so it’s really important for providers to know that stroke risk is higher in those patients, particularly in those children, and then identify it and treat it earlier. Time is of the essence, and if we can give them the same therapeutics that we give the general stroke population, then time really becomes a factor, so it’s important that people know that it’s an issue for this population,” said Eboni Lance, MD, PhD, who coordinated the session where Dr. Jordan spoke.

Sickle cell disease is caused by a double mutation in the gene encoding the hemoglobin gene, producing the altered sickle hemoglobin (hemoglobin S). The change causes the hemoglobin proteins to tend to stick to one another, which can lead red blood cells to adopt a sickle-like shape. The sickle-shaped blood cells in turn have a tendency to aggregate and can block blood flow or lead to endothelial injury. Symptoms of stroke in children can include hemiparesis, aphasia, and seizure, but they can also be silent.

If no preventive is employed, one in nine with sickle cell disease will experience a stroke by the age of 19. Cerebrovascular symptoms are the most frequent debilitating complication of the condition. Nearly 40% of patients with sickle cell disease will have a silent cerebral infarct by age 18, as will 50% by age 30. Silent strokes have been associated with worse educational attainment and a greater need for educational special services.

Factors contributing to stroke in children with sickle cell disease include anemia and a low blood oxygen count, reduced oxygen affinity of hemoglobin variant, and cerebral vasculopathy. An estimated 10%-15% of young adults with sickle cell disease have severe intracranial stenosis.
 

Primary and secondary stroke prevention strategies

The dire consequences of stroke in this patient population underline the importance of primary stroke prevention, which requires the use of transcranial Doppler (TCD) ultrasound. It has been validated as a tool to screen for initial stroke risk in children with no history of stroke. High velocity measured on TCD indicates a narrowed blood vessel or elevated blood that is compensating for anemia. It adds up to a “struggling brain,” said Dr. Jordan, during her talk. If the TCD ultrasound velocity is greater than 200 cm/sec (or 170 cm/sec, depending on nonimaging versus imaging TCD), the TWiTCH trial showed that seven monthly transfusions is the number needed to treat to prevent one stroke. After 1 year, patients can be switched from transfusions to hydroxyurea if the patient has no significant intracranial stenosis. Hydroxyurea boosts both fetal and total hemoglobin, and also counters inflammation.

Following an acute stroke or transient ischemic attack, patients should receive a transfusion within 2 hours of presenting in the health care setting. American Society of Hematology guidelines recommend exchange transfusion rather than a simple transfusion. A simple transfusion can be initiated if an exchange transfusion is not available within 2 hours and hemoglobin values are less than 8.5 g/dL, to be followed by performance of exchange transfusion when available.

For chronic secondary stroke prevention, transfusions should be performed approximately monthly with the goal of maintaining hemoglobin above 9 g/dL at all times, as well as suppressing hemoglobin S levels to 30% or less of total hemoglobin.

Sudden, severe headache is a potential harbinger of complications like aneurysm, which occurs 10-fold more often among patients with sickle cell disease than the general population. It could also indicate increased intracranial pressure or cerebral venous sinus thrombosis.

Treatment of acute headache in sickle cell disease should avoid use of triptans, since vasoconstriction can counter the increased cerebral blood flow that compensates for anemia. Gabapentin and amitriptyline are good treatment choices.

New-onset seizures are a potential sign of stroke or posterior reversible leukoencephalopathy (PRES) in patients with sickle cell disease. Urgent MRI should be considered for all new-onset seizures. If blood pressure is high, PRES may be present. Seizures may also be an indicator of a previous brain injury.

Dr. Jordan has no relevant financial disclosures. Dr. Lance has served on an advisory board for Novartis.
 

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.

DENVER – Use of subcutaneous ropivacaine for Mohs surgery in highly vascularized anatomical regions such as the nose results in significantly shorter duration of anesthesia compared with less vascularized regions such as the shin, results from a single-center study showed.

Ropivacaine is a long-acting anesthetic that may be used as a substitute for the more commonly local anesthetics such as lidocaine or bupivacaine in dermatologic surgery, lead study author Kira Minkis, MD, PhD, told this news organization following the annual meeting of the American Society for Dermatologic Surgery, where the study results were presented during an oral abstract session. By comparison, ropivacaine has been reported to have a faster onset, similar duration in the range of 6-14 hours, less pain upon injection, and inherent vasoconstrictive properties.

“With tumescent anesthesia, studies have previously shown that the rate and absorption of anesthetics is influenced by the site of administration,” said Dr. Minkis, director of Mohs and dermatologic surgery at Weill Cornell Medicine, New York. “In studies comparing absorption of local anesthetics in tumescent anesthesia by regions that differ in vascularity, peak serum concentrations are greater and rise more rapidly after use in the head and neck compared to the trunk and extremities. However, no studies to date have compared the duration of ropivacaine in highly vascularized tissue or compared duration between regions that differ in vascularity.” The aim of the study, she noted, was to characterize the difference in duration of ropivacaine’s effects between anatomic regions of rich and comparably poor vascularity, such as the face and extremities, respectively.

Dr. Minkis and her colleagues recruited 17 women and 12 men with a mean age of 72 years who underwent Mohs surgery on the nose or the shin at Weill Cornell Medicine. Patients were anesthetized at each site with a subcutaneous injection of 0.5 mL of ropivacaine, 0.2%. Sensation was determined by pinprick prior to injection, at baseline, and every 15 minutes until sensation returned or surgery concluded. The primary endpoint was time to return of pinprick sensation.

The researchers found that the duration of ropivacaine was significantly shorter on the nose (a median of 60 minutes) than on the shin (a median of 210 minutes). In fact, the upper limit of the range of duration at the shin was not determinable because 22 of the 29 (76%) of participants did not regain sensation on the shin prior to leaving the surgical suite and concluding the study. The proportion of study participants who regained sensation within 1 hour was 76% among those who were treated on the nose vs. 3% of those who were treated on the shin (P < .0001).

“With durations of up to 6-14 hours reported, our results indicate a strikingly shorter duration of local anesthesia in highly vascularized tissue,” Dr. Minkis said. “The brevity of local anesthesia is even more surprising given the intrinsic vasoconstrictive properties of ropivacaine. Often, we co-administer epinephrine to achieve vasoconstriction and reduce local blood flow, thus prolonging local concentrations of the anesthetic with the added benefit of reducing bleeding during surgery. The short duration we’ve observed in our study is emphasized in using a potent, long-acting local anesthetic with vasoconstrictive properties that otherwise should attenuate the effects of high local vascularity.”

In other findings, patients with history of hypertension were more likely to regain sensation on the nose by 60 minutes but this did not reach statistical significance (P = .079). Other comorbidities including underlying anxiety/depression, diabetes, and kidney disease did not significantly impact duration of ropivacaine action on the nose. The same held true for patients who were treated on the shin.

“We highlight an inconsistency between the reported duration of a long-lasting local anesthetic and the short-lived anesthesia experienced by our patients in a highly vascularized region,” Dr. Minkis said. “In practice, adjunctive use of a long-acting anesthetic to prolong anesthesia is common, which may provide relief from multiple injections of shorter-acting lidocaine. However, the duration of Mohs surgery can be unpredictable. Extended wait times between stages may exceed the duration we’ve observed in this study.”

In addition, she continued, “pain is frequently reported on postoperative days 0 to 3, leading some to recommend the use of long-acting local anesthetics to prevent overprescription or a gap in pain coverage. This emphasizes a gap in effective pain control, but also an opportunity to improve our patients’ surgical and recovery experiences.”

 

Impact on practice

Keith L. Duffy, MD, associate professor of dermatology at the University of Utah, Salt Lake City, who was asked to comment on the study, said that in light of current local anesthetic shortages and back orders, “we dermatologic surgeons have been experimenting with different anesthetics and concentrations that we can use in our patients. Ropivacaine may become the anesthetic of choice for many of our practices given its inherent properties.”

The duration of anesthetic effects by anatomic location in this study is “actually more impressive than I would have suspected as a practicing Mohs surgeon. The results of this study will immediately impact my Mohs surgery clinic,” he said, adding that he hoped that Dr. Minkis and others “will expand on this study to include more patients, different anesthetics, and more anatomic locations.”

Dr. Minkis acknowledged certain limitations of the study, including its single-center design and the fact that there were too few observations of medical and clinical characteristics for subgroup analysis.

She and Dr. Duffy reported having no financial disclosures.

DENVER – One expert’s clinical experience suggests that Ellacor, a dermal microcoring device that became available in the United States in October 2022, is an effective treatment for facial wrinkles and tightening.

“It’s early yet, but I have treated dozens of patients with this device, and they have been happy with the results,” Mathew M. Avram, MD, JD, said at the annual meeting of the American Society for Dermatologic Surgery. “This is a new technique that offers the ability to remove a significant amount of damaged, lax skin without concern for scarring,” he said.

A brainchild of dermatologists and plastic surgeons at Massachusetts General Hospital, Boston, the first-in-class device is cleared by the Food and Drug Administration for the treatment of moderate and severe wrinkles in the mid and lower face in adults aged 22 years or older with Fitzpatrick skin types I-IV. It features a proprietary needle design that makes a series of high throughput microexcisions in epidermal and dermal tissue, with minimal downtime and without using thermal energy.

“It doesn’t do anything equivalent to a facelift, but the concept is a facelift by thousands of micro-punch excisions,” said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital. “Rather than pulling up the skin and lifting it and cutting the excess skin like we do with a facelift, we are creating thousands of smaller-scale tissue removals with immediate closures to do the same thing. The micro-cores are about the size of a 22-gauge needle and there is no scarring due to the small size of these tissue extractions.”

The device features needle cartridges capable of excising up to 24,000 cores per treatment. According to data from Cytrellis, the manufacturer, the equivalent of about 2 inches of skin can be removed during the procedure, which typically takes fewer than 30 minutes to perform. “There is no heat whatsoever,” Dr. Avram said. “In my experience, it especially helps with jawline definition, the lower medial cheek excess skin, and accordion lines in that area.”

In a pivotal trial of the device, 51 patients with mid to lower face wrinkles (moderately deep or deep wrinkles with well-defined edges) were treated 2-3 times with 7%-8% skin removal and up to a 5-mm needle coring depth). The investigators found that 40% of study participants achieved an improvement of 2 grades on the Lemperle Wrinkle Severity Scale and that the rate of overall satisfaction (slightly, somewhat, and extremely satisfied) was 86%.

In addition, 90% showed improvement of treated sites on the Global Aesthetic Improvement Scale, and 70% were comfortable enough to go out in public or return to work 3 days after treatment. Common side effects that can occur immediately post treatment include redness, swelling, and pinpoint bleeding, which typically clear in a few days.

Dr. Avram, immediate past president of the ASDS, has posted videos to his Instagram feed that show him treating patients with the Ellacor device and he admits that the procedure looks painful. “There are all these tear emojis and people cursing me out,” he said, referring to responses from his Instagram followers.

Proper local anesthesia prior to treatment is key. “I perform nerve blocks and infiltrate the skin,” he said. “You have to cover the whole treatment area. If you don’t, then it’s going to hurt. The average pain score is 1.9 out of 10. The highest pain score I’ve gotten from a patient is a 3 out of 10.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton, and has ownership and/or shareholder interest in Cytrellis.

DENVER – One expert’s clinical experience suggests that Ellacor, a dermal microcoring device that became available in the United States in October 2022, is an effective treatment for facial wrinkles and tightening.

“It’s early yet, but I have treated dozens of patients with this device, and they have been happy with the results,” Mathew M. Avram, MD, JD, said at the annual meeting of the American Society for Dermatologic Surgery. “This is a new technique that offers the ability to remove a significant amount of damaged, lax skin without concern for scarring,” he said.

A brainchild of dermatologists and plastic surgeons at Massachusetts General Hospital, Boston, the first-in-class device is cleared by the Food and Drug Administration for the treatment of moderate and severe wrinkles in the mid and lower face in adults aged 22 years or older with Fitzpatrick skin types I-IV. It features a proprietary needle design that makes a series of high throughput microexcisions in epidermal and dermal tissue, with minimal downtime and without using thermal energy.

“It doesn’t do anything equivalent to a facelift, but the concept is a facelift by thousands of micro-punch excisions,” said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital. “Rather than pulling up the skin and lifting it and cutting the excess skin like we do with a facelift, we are creating thousands of smaller-scale tissue removals with immediate closures to do the same thing. The micro-cores are about the size of a 22-gauge needle and there is no scarring due to the small size of these tissue extractions.”

The device features needle cartridges capable of excising up to 24,000 cores per treatment. According to data from Cytrellis, the manufacturer, the equivalent of about 2 inches of skin can be removed during the procedure, which typically takes fewer than 30 minutes to perform. “There is no heat whatsoever,” Dr. Avram said. “In my experience, it especially helps with jawline definition, the lower medial cheek excess skin, and accordion lines in that area.”

In a pivotal trial of the device, 51 patients with mid to lower face wrinkles (moderately deep or deep wrinkles with well-defined edges) were treated 2-3 times with 7%-8% skin removal and up to a 5-mm needle coring depth). The investigators found that 40% of study participants achieved an improvement of 2 grades on the Lemperle Wrinkle Severity Scale and that the rate of overall satisfaction (slightly, somewhat, and extremely satisfied) was 86%.

In addition, 90% showed improvement of treated sites on the Global Aesthetic Improvement Scale, and 70% were comfortable enough to go out in public or return to work 3 days after treatment. Common side effects that can occur immediately post treatment include redness, swelling, and pinpoint bleeding, which typically clear in a few days.

Dr. Avram, immediate past president of the ASDS, has posted videos to his Instagram feed that show him treating patients with the Ellacor device and he admits that the procedure looks painful. “There are all these tear emojis and people cursing me out,” he said, referring to responses from his Instagram followers.

Proper local anesthesia prior to treatment is key. “I perform nerve blocks and infiltrate the skin,” he said. “You have to cover the whole treatment area. If you don’t, then it’s going to hurt. The average pain score is 1.9 out of 10. The highest pain score I’ve gotten from a patient is a 3 out of 10.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton, and has ownership and/or shareholder interest in Cytrellis.

DENVER – One expert’s clinical experience suggests that Ellacor, a dermal microcoring device that became available in the United States in October 2022, is an effective treatment for facial wrinkles and tightening.

“It’s early yet, but I have treated dozens of patients with this device, and they have been happy with the results,” Mathew M. Avram, MD, JD, said at the annual meeting of the American Society for Dermatologic Surgery. “This is a new technique that offers the ability to remove a significant amount of damaged, lax skin without concern for scarring,” he said.

A brainchild of dermatologists and plastic surgeons at Massachusetts General Hospital, Boston, the first-in-class device is cleared by the Food and Drug Administration for the treatment of moderate and severe wrinkles in the mid and lower face in adults aged 22 years or older with Fitzpatrick skin types I-IV. It features a proprietary needle design that makes a series of high throughput microexcisions in epidermal and dermal tissue, with minimal downtime and without using thermal energy.

“It doesn’t do anything equivalent to a facelift, but the concept is a facelift by thousands of micro-punch excisions,” said Dr. Avram, director of laser, cosmetics, and dermatologic surgery at Massachusetts General Hospital. “Rather than pulling up the skin and lifting it and cutting the excess skin like we do with a facelift, we are creating thousands of smaller-scale tissue removals with immediate closures to do the same thing. The micro-cores are about the size of a 22-gauge needle and there is no scarring due to the small size of these tissue extractions.”

The device features needle cartridges capable of excising up to 24,000 cores per treatment. According to data from Cytrellis, the manufacturer, the equivalent of about 2 inches of skin can be removed during the procedure, which typically takes fewer than 30 minutes to perform. “There is no heat whatsoever,” Dr. Avram said. “In my experience, it especially helps with jawline definition, the lower medial cheek excess skin, and accordion lines in that area.”

In a pivotal trial of the device, 51 patients with mid to lower face wrinkles (moderately deep or deep wrinkles with well-defined edges) were treated 2-3 times with 7%-8% skin removal and up to a 5-mm needle coring depth). The investigators found that 40% of study participants achieved an improvement of 2 grades on the Lemperle Wrinkle Severity Scale and that the rate of overall satisfaction (slightly, somewhat, and extremely satisfied) was 86%.

In addition, 90% showed improvement of treated sites on the Global Aesthetic Improvement Scale, and 70% were comfortable enough to go out in public or return to work 3 days after treatment. Common side effects that can occur immediately post treatment include redness, swelling, and pinpoint bleeding, which typically clear in a few days.

Dr. Avram, immediate past president of the ASDS, has posted videos to his Instagram feed that show him treating patients with the Ellacor device and he admits that the procedure looks painful. “There are all these tear emojis and people cursing me out,” he said, referring to responses from his Instagram followers.

Proper local anesthesia prior to treatment is key. “I perform nerve blocks and infiltrate the skin,” he said. “You have to cover the whole treatment area. If you don’t, then it’s going to hurt. The average pain score is 1.9 out of 10. The highest pain score I’ve gotten from a patient is a 3 out of 10.”

Dr. Avram disclosed that he has received consulting fees from Allergan, Merz, Sciton, and Soliton, and has ownership and/or shareholder interest in Cytrellis.

The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.

“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.

Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.

He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.

That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.

Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.

In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.

In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.

Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.

The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.

Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.

“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.

Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.

Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.

International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.

None of the presenters have relevant financial disclosures.

The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.

“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.

Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.

He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.

That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.

Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.

In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.

In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.

Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.

The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.

Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.

“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.

Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.

Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.

International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.

None of the presenters have relevant financial disclosures.

The effects of the Russian invasion of Ukraine have been devastating, with the loss of tens of thousands of civilian lives and about one-third of the population having been displaced. The war has put a great strain on health care in the country.

“The Russian army is targeting civilian infrastructure, trying to plunge Ukrainians into cold and darkness. (It) is also deliberately targeting hospitals and clinics in Ukraine,” said Nataliya Kovalchuk, PhD, during a session on Ukraine health care at the annual meeting of the American Society for Radiation Oncology held this week in San Antonio. She is a clinical associate professor of radiation oncology at Stanford (Calif.) University.

Analysis of previous wars have shown an increase in cancer incidence and mortality, and the same should be expected in the future in Ukraine, according to Ruslan Zelinskyi, MS, who is president of the Ukrainian Association of Medical Physicists and practices at Spizhenko Clinic in Ukraine. “We must prepare for it now, and we do it. During the full-scale war in Ukraine, three new linear accelerators were installed and put into clinical use,” he said during his talk.

He also gave a personal perspective of the terrible conditions and choices facing Ukrainian health care workers. “I have often heard that science is outside of politics. Perhaps in peacetime, but when fragments of missiles pass through the wall” – here, Mr. Zelinskyi paused to swing the camera around to show bomb damage on the walls of the room where he was conducting his virtual talk – “it is impossible to be outside of politics when 900 medical facilities were destroyed or damaged.” Health care workers have been killed, and patients have lost months or years because they could not receive medical care.

That reality is forcing Ukrainians to make choices most health care workers would struggle to imagine. “For many years, I put on medical clothes and fight against cancer. But (for) me comes the moment when I will change my medical clothes to military (clothes), like many, many other Ukrainians of various professions, because we must preserve the freedom of Ukraine and the security of Europe to do science in a peaceful world,” Mr. Zelinskyi said.

Following Mr. Zelinskyi’s talk, Asya Agulnik, MD, MPH, director of the St. Jude’s Global Critical Care Program and a pediatric intensivist at St. Jude’s Children’s Research Hospital, Memphis, described St. Jude’s efforts with pediatric cancer patients. St. Jude’s Global Critical Care Program created a Eurasian Regional Program in 2018 to serve Central Asia and Eastern Europe, which now includes 48 institutions and more than 250 clinicians and members that help care for children with cancer.

In the aftermath of the invasion, the Eurasian Regional Program launched the Safer Ukraine network to ensure continued care for children with cancer and blood disorders. Initially, the patient’s family or physician identifies a child has having a medical need that cannot be met locally and requiring evacuation. The nongovernmental organization Tabletochki, which has worked with children with cancer in Ukraine since 2011, then arranges transport of the child and his or her medical records to the Ukrainian Specialized Children’s Center in Lviv, Ukraine, for evaluation and stabilization. From there, patients along with their mother and sometimes siblings are transferred to Poland. Transportation methods include ambulance, helicopter, bus, and medical trains that have a full intensive care unit aboard.

In Poland, hospitals estimated they could take on another 200 patients without compromising care for their existing patients, but evacuations reached that number within the first few weeks of the war. It was clear patients would have to be transferred to other countries. To do that, Safer Ukraine set up the Unicorn Marian Wilemski Clinic, which is a converted hotel operated as a partnership between many foundations and governments. It sends unstable patients to nearby emergency rooms, and stable patients stay at the clinic until they can be evaluated and matched with an international care provider from a registry of more than 200 hospitals in 29 countries that have agreed to take patients. A 24/7 Zoom call began on the first day of the war, initially staffed by St. Jude volunteers and now by a contractor. It serves as a command center.

Over the first 12 weeks of the war, the program evacuated over 1,000 children, and over 200 medical records per week were being translated at peak activity. Nearly 300 patients went to Poland, and the rest to 18 countries in Europe and North America.

The success of the initiative stems in part from the fact that it leveraged preexisting collaborations that focused on childhood cancer, according to Dr. Agulnik. “Many stakeholders that came together had previously worked together, but then quickly came together around this unified initiative with the goal of helping these patients,” she said during her talk.

Roman Kowalchuk, MD, who is a radiation oncology resident at Mayo Clinic, spoke about telemedicine efforts to assist physicians and patients in Ukraine.

“I’ve been especially interested in trying to help through telemedicine. We have so much expertise, so many things that we can offer, even if we can’t be there physically, through some of these avenues that really, especially through COVID, have been further developed in terms of virtual support, virtual expertise, and consultations. That presents the opportunity to be able to share some of that knowledge, some of that expertise, to help clinical care in Ukraine given the current circumstance,” said Dr. Kowalchuk during his presentation.

Efforts have used technology like the telemedicine platform Viveo, based in Estonia. One app, called HealUA, takes descriptions from physicians needing advice, and volunteers can scroll through inquiries and provide input. This is especially useful since most physicians in Ukraine are generalists, according to Dr. Kowalchuk, and so may need assistance with diagnosis and management of rare conditions.

Other telehealth approaches include TeleHelp Ukraine. There are WhatsApp groups with hundreds of volunteers who translate Ukrainian medical records to other languages to help non-Ukrainian physicians understand a patient’s history. Expertise is also needed in engineering, emergency medicine, surgery, various fields of oncology, and other specialties. Dr. Kowalchuk noted that Good Samaritan laws generally shield volunteers in these types of programs from legal liability.

International hospital networks taking part in these efforts include St. Jude, European Cancer Organization, American Cancer Society, American Society for Clinical Oncology, and ASTRO.

None of the presenters have relevant financial disclosures.

CHARLOTTE, N.C. – Several factors appear to influence the risk for acute pancreatitis among patients who start taking glucagon-like peptide (GLP-1) receptor agonist medications for weight management, a new study has found.

Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.

On the other hand, a higher body mass index (BMI) – 36 kg/m² or higher – appeared to protect people against developing the condition.

“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.

The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
 

Popularity comes at a price

The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).

The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.

Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.

Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m².

The study only included patients starting GLP-1s for treating obesity, not for diabetes.

Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.

A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).

Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).

In contrast, researchers found those with a BMI of 36-40 kg/m² were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m². Patients with a BMI of greater than 40 kg/m² had a 73% lower risk (95% CI, 0.10-0.73; P = .01).

Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.

Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”

“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.

“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
 

Larger studies needed

The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.

However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.

“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.

Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.

Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.

Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.

The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.

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

CHARLOTTE, N.C. – Several factors appear to influence the risk for acute pancreatitis among patients who start taking glucagon-like peptide (GLP-1) receptor agonist medications for weight management, a new study has found.

Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.

On the other hand, a higher body mass index (BMI) – 36 kg/m² or higher – appeared to protect people against developing the condition.

“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.

The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
 

Popularity comes at a price

The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).

The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.

Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.

Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m².

The study only included patients starting GLP-1s for treating obesity, not for diabetes.

Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.

A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).

Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).

In contrast, researchers found those with a BMI of 36-40 kg/m² were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m². Patients with a BMI of greater than 40 kg/m² had a 73% lower risk (95% CI, 0.10-0.73; P = .01).

Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.

Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”

“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.

“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
 

Larger studies needed

The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.

However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.

“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.

Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.

Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.

Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.

The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.

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

CHARLOTTE, N.C. – Several factors appear to influence the risk for acute pancreatitis among patients who start taking glucagon-like peptide (GLP-1) receptor agonist medications for weight management, a new study has found.

Type 2 diabetes, advanced chronic kidney disease, and tobacco use were associated with greater risk for acute pancreatitis, researchers report.

On the other hand, a higher body mass index (BMI) – 36 kg/m² or higher – appeared to protect people against developing the condition.

“As this class of medications becomes increasingly popular in the United States, it is important for providers to know which patients are at a higher or lower risk of developing acute pancreatitis after being started on them,” said lead study author Robert Postlethwaite, MD, a gastroenterology resident at the University of Texas Southwestern Medical Center, Dallas.

The findings were presented at the annual meeting of the American College of Gastroenterology in Charlotte, N.C., being held in person and virtually.
 

Popularity comes at a price

The U.S. Food and Drug Administration has approved two GLP-1s for weight management – liraglutide (Victoza) in 2014 and semaglutide (Wegovy) in 2021. They work by targeting areas of the brain that control food intake and appetite. Other GLP-1s approved to treat type 2 diabetes include dulaglutide (Trulicity) and two other formulations of semaglutide (Rybelsus and Ozempic).

The demand for Wegovy has been so great that there is an ongoing shortage of the medication in the United States.

Although GLP-1s demonstrate a favorable side-effect profile, compared with other types of antiobesity medications, acute pancreatitis remains a serious and sometimes life-threatening complication, the researchers note. Some patients require hospitalization.

Dr. Postlethwaite and colleagues performed a retrospective, single-center study of 2,245 patients who attended an academic medical center’s Weight Wellness program from 2015 to 2019. The average age was about 50 years, and 81% were female. The average BMI of all patients was 39.7 kg/m².

The study only included patients starting GLP-1s for treating obesity, not for diabetes.

Of the 2,245 patients, 49 (2.2%) developed acute pancreatitis after starting a GLP-1.

A history of type 2 diabetes mellitus made acute pancreatitis twice as likely (95% confidence interval, 1.04-3.96; P = .04).

Stage 3 or higher chronic kidney disease increased risk 2.3 times (95% CI, 1.18-4.55; P = .01), while tobacco use upped it 3.3 times (95% CI, 1.70-6.50; P < .001).

In contrast, researchers found those with a BMI of 36-40 kg/m² were 88% less likely to develop acute pancreatitis (95% CI, 0.07-0.67; P = .007), compared with patients with a BMI of less than or equal to 30 kg/m². Patients with a BMI of greater than 40 kg/m² had a 73% lower risk (95% CI, 0.10-0.73; P = .01).

Dr. Postlethwaite and colleagues found no association with age, sex, or history of bariatric surgery or acute pancreatitis.

Because a history of acute pancreatitis was not a risk factor, he advised that clinicians not withhold these medications for this reason, “especially given the significant glycemic, cardiovascular, and weight-loss effects.”

“We hope that we can arm clinicians with evidence in order to risk stratify their patients and determine who is at high risk of developing pancreatitis,” Dr. Postlethwaite said.

“Hopefully, we can prevent the development of pancreatitis in some patients, especially high-risk individuals, or at least allow clinicians to be aware of it in higher-risk patients to identify it early enough to prevent complications of acute pancreatitis,” he added.
 

Larger studies needed

The study is “promising,” said session comoderator Baharak Moshiree, MD, a gastroenterologist at Atrium Health, Charlotte, N.C., who was not affiliated with the research.

However, because the study was retrospective and relatively small, it needs to be validated in larger, prospective studies, she added.

“With obesity being such a global issue, there are many patients on these GLP-1 agonists,” Dr. Moshiree said.

Generally, these medications are prescribed by endocrinologists, not gastroenterologists, she noted, and she said that gastroenterologists should be aware of the risks associated with them, including minor gastrointestinal side effects, like nausea and vomiting, that can occur because of delayed gastric emptying.

Dr. Postlethwaite noted that being unable to assess how much alcohol or tobacco individuals used was a limitation. The relatively low proportion of people who developed acute pancreatitis in the study also means larger studies are warranted, he added.

Going forward, Dr. Postlethwaite and colleagues want to study the risks for each individual GLP-1 and other therapies used to control high blood sugar in people with type 2 diabetes, such as DPP4 (dipeptidyl-peptidase 4) inhibitors.

The study was independently supported. Dr. Postlethwaite and Dr. Moshiree report no relevant financial relationships.

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

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

The relationship between estrogen levels and heart health makes it particularly important for clinicians to be aware of those patients who might be at risk for cardiovascular disease despite not having other traditional risk factors, according to a presentation Oct. 12 at the North American Menopause Society annual meeting in Atlanta.

”Endogenous estrogens are protective for cardiovascular disease in premenopausal women,” Chrisandra L. Shufelt, MD, chair of the division of general internal medicine and associate director of the Women’s Health Research Center at Mayo Clinic in Jacksonville, Fla., told attendees. Yet, “a substantial population of young women are dying prematurely from cardiovascular disease,” with rates of cardiovascular death increasing in women aged 35-44 even as rates have decreased in postmenopausal women and in men. One potential reason may be premature estrogen loss.

Dr. Shufelt reminded attendees of four major causes of premature estrogen loss: Natural premature menopause, surgical menopause, chemotherapy-induced menopause, and premature ovarian insufficiency. But she would go on to discuss a less widely recognized condition, functional hypothalamic amenorrhea, that also may be contributing to increased cardiovascular risk.

First, Dr. Shufelt reviewed the evidence supporting the relationship between estrogen and cardiovascular health, starting with the Framingham study’s findings that cardiovascular disease is approximately two to four times more common in postmenopausal women than in premenopausal women, depending on the age range.

“Menopause at an early age, particularly under the age of 40, matters,” Dr. Shufelt said. “So we should be discussing this with our patients.”

Surgical menopause makes a difference to cardiovascular health as well, she said. In women under age 35, for example, the risk of a nonfatal heart attack in those with a bilateral oophorectomy was 7.7 times greater than in women who retained both ovaries and their uterus, and 1.5 times greater in women who had a hysterectomy without bilateral oophorectomy.

In a 2019 study, surgical premature menopause was associated with an 87% increased risk of heart disease even after researchers accounted for age, cardiovascular risk factors, and some forms of hormone therapy. The increased risk from natural premature menopause, on the other hand, was lower – a 36% increased risk of heart disease – compared with those producing endogenous hormones. Although randomized controlled trials are unavailable and unlikely to be done, the Nurses’ Health Study and the Danish Nurses Cohort Study, both observational studies, found that heart disease risk was diminished in those taking hormone therapy after surgical premature menopause.

Recommendations for premature or early menopause, from a wide range of different medical societies including NAMS, are that women without contraindications be given estrogen-based hormone therapy until the average age of natural menopause. Though not included in the same guidance, research has also shown that estrogen after oophorectomy does not increase the risk of breast cancer in women with a BRCA1 mutation, Dr. Shufelt said. Hormone therapy for premature or early menopause should adequately replace the levels women have lost and that means younger menopausal women often need higher doses than what older women receive, such as 2 mg/day of oral estradiol rather than the standard doses of 0.5 or 1 mg/day.
 

Functional hypothalamic amenorrhea and cardiovascular risk

Dr. Shufelt then discussed functional hypothalamic amenorrhea (hypogonadotropic hypogonadism), a common type of secondary amenorrhea that affects at least 1.4 million U.S. women. Diagnosis includes lack of a period for at least 3 months in someone who previously menstruated plus lab values below 50 pg/mL for estradiol, below 10 mIU/L for follicle stimulating hormone, and below 10 mIU/L for luteinizing hormone. Causes of this reversible form of infertility can include stress, overexercising, undereating, or some combination of these, plus an underlying genetic predisposition.

“After ruling out polycystic ovary syndrome, prolactinoma, and thyroid dysfunction, clinicians need to consider the diagnosis of hypothalamic amenorrhea,” Dr. Shufelt said. This condition goes beyond low estrogen levels: Women have elevated cortisol, low thyroid levels, low leptin levels, and increased ghrelin.

”This is not going away,” Dr. Shufelt said, sharing data on stress levels among U.S. adults, particularly Gen Z and millennial adults, noting that the ongoing “national mental health crisis” may be contributing to functional hypothalamic amenorrhea.

A 2020 substudy from the Nurses’ Health Study II found an increased risk of premature death in those who didn’t have a period or always had irregular periods starting as early as 14-17 years old. The increased risk of premature death rose with age in those with irregular or absent cycles – a 37% higher risk in 18- to 22-year-olds and a 39% increased risk in 29- to 46-year-olds.

But clinicians aren’t adequately identifying the “phenotype of the hypothalamic women,” Dr. Shufelt said, despite research showing overlap between hypothalamic amenorrhea and a higher risk of cardiovascular disease. Hypothalamic amenorrhea is so understudied that the last original research on the topic was in 2008, Dr. Shufelt said in an interview. ”No research except mine has been done to evaluate heart health in these young women,” she said.

Dr. Shufelt described a study she led involving 30 women with functional hypothalamic amenorrhea, 29 women with normal menstrual cycles, and 30 women who were recently menopausal and not on hormone therapy. The women with hypothalamic amenorrhea had average stress levels but their depression scores were higher than those of the other two groups.

The results showed that women with hypothalamic amenorrhea had lower estradiol and leptin levels and higher testosterone levels compared with the control group, and they had higher cortisol levels than those of both groups. Despite having similar body mass indexes as the control and menopausal groups, women with hypothalamic amenorrhea had lower blood pressure than that of the other two groups, yet they had higher cholesterol levels than those of the control group. EndoPAT^© (Itamar Medical) testing showed that they had poor vascular function.

“In fact, one-third of the women [with hypothalamic amenorrhea] entered the trial with a diagnosis of what would be considered endothelial dysfunction,” Dr. Shufelt said. “Our results demonstrated significantly higher circulating levels of serum proinflammatory cytokines in the women with hypothalamic amenorrhea compared to eumenorrheic controls.”

Dr. Shufelt’s team then tested whether giving estradiol to the women with hypothalamic amenorrhea for 12 weeks would improve their vascular health, but they saw no significant differences between the women who received estrogen and those who received placebo.

“Endothelial function is partly mediated by estrogen, and it was expected that giving back estrogen would ‘fix’ the endothelium, but that is not what happened,” Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado at Denver, Aurora, said in interview. “The mechanisms that maintain vascular function in women are not limited to hormones,” said Dr. Santoro, who was not involved in Dr. Shufelt’s study but attended her lecture. “We need to think beyond the simple model of estrogen-good, no-estrogen-bad.”

Dr. Santoro noted how easy it is to overlook the women who may have cardiovascular risk because of hypothalamic amenorrhea.

“Because many women with functional hypothalamic amenorrhea are super athletic and do not have the typical features of people with cardiometabolic disease – such as glucose intolerance, obesity, abnormal cholesterol or triglycerides, or high blood pressure – clinicians tend to think of them as healthy and to think that simply giving back hormones will fix the problems with bone density and vascular function, but that is not enough,” Dr. Santoro said. “The cognitive-behavioral therapy model for treatment of women with functional hypothalamic amenorrhea addresses the stress-related factors that drive the disorder, and this needs to be considered the standard of care for treatment.”

Stephanie S. Faubion, MD, professor of medicine and director of Mayo Clinic’s Center for Women’s Health in Jacksonville, Fla., who was not involved in Dr. Shufelt’s presentation, also emphasized the importance of recognizing functional hypothalamic amenorrhea.

“This is an underrecognized entity to begin with, and the fact that these women appear to be at increased risk for vascular dysfunction and potentially increased risk for cardiovascular disease down the road makes it even more important for clinicians to identify them and provide interventions early on,” Dr. Faubion said in an interview. “These women need to be identified and the etiology of the amenorrhea addressed, whether it relates to overexercising, being underweight, or experiencing significant stressors that have led to the loss of menstrual cycles.”

Dr. Shufelt’s research was funded by the National Institutes of Health. She had no disclosures. Dr. Santoro is a member of the scientific advisory board for Astellas, Menogenix, Amazon Ember, and Que Oncology, and she consults for Ansh Labs. Dr. Faubion had no disclosures.

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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

MONTREAL – Remote assessment of atopic dermatitis (AD) severity is possible through the use of patient-provided clinical photos – opening a new avenue for improving access for patients, as well as the possibility of conducting remote clinical trials that would be less expensive and less burdensome for participants, according to investigators, who presented the study at the annual meeting of the International Society of Atopic Dermatitis.

Still, practical barriers need to be addressed, particularly the problem of image quality, noted study investigator Aviël Ragamin, MD, from the department of dermatology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

“Good-quality images are crucial, [and] in our study, patients didn’t have any incentive to provide images because they had already received their medical consultation,” he explained. He suggested that this problem could be overcome by providing technical support for patients and compensation for trial participants.

The study included 87 children (median age, 7 years), who were assessed for AD severity at an academic outpatient clinic. The in-person visit included assessment with the Eczema Area and Severity Index (EASI) score, as well as the collection of whole-body clinical images. Parents were then asked to return home and to provide their own clinical images and self-administered EASI assessments of their child for comparison. Four raters were asked to rate all images twice and to compare in-clinic and self-administered EASI scores based on the images.

At the in-clinic visit, the median EASI score of the group was 8.8. The majority of patients had moderate (46.6%) or severe (14.8%) AD. Roughly 40% of the patients had darker skin (Fitzpatrick skin types IV–VI).

Using Spearman rank correlation of 1,534 in-clinic and 425 patient-provided images, the study found good inter- and intra-rater reliability for clinical image assessment and strong agreement between images and the in-clinic EASI scores. The top outliers in the assessment were individuals with either darker skin or significant postinflammatory hyperpigmentation, which are “the most difficult cases to rate, based on images,” Dr. Ragamin noted.

There was only moderate correlation between the in-clinic and self-administered EASI scores, with a significant number of patients either underestimating or overestimating their AD severity, he added.

Overall, the main problem with remote assessment seems to be the feasibility of patients providing images, said Dr. Ragamin. Only 36.8% of parents provided any images at all, and of these, 1 of 5 were deemed too blurry, leaving just 13 for final assessment, he explained.

“Pragmatically, it’s tricky,” said Aaron Drucker, MD, a dermatologist at Women’s College Hospital and associate professor at the University of Toronto, who was asked to comment on the study. “It takes long enough to do an EASI score in person, let alone looking through blurry pictures that take too long to load into your electronic medical record. We know it works, but when our hospital went virtual [during the COVID pandemic] ... most of my patients with chronic eczema weren’t even sending me pictures.”

Regarding the utility of remote, full-body photography in clinical practice, he said, “There’s too many feasibility hoops to jump through at this point. The most promise I see is for clinical trials, where it’s hard to get people to come in.”

Dr. Ragamin and Dr. Drucker have disclosed no relevant financial relationships.

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