Dermatology News

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

Patients who are immunocompromised showed no increased risk of surgical site infection when undergoing Mohs micrographic surgery, regardless of whether or not they received antibiotics, suggesting that antibiotic prophylaxis, which is often used for these patients, may not be necessary, according to new research.

The retrospective cohort study found that “immunosuppressed patients had similar infection rates as immunocompetent patients following Mohs micrographic surgery,” first author Tuyet A. Nguyen, MD, of the department of dermatology, Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Therefore, antibiotic prescribing patterns should not change simply due to immunosuppression. Furthermore, immunosuppressed patients appear to respond well to antibiotics and recover similarly to immunocompetent patients,” she said.

Dr. Nguyen

Overall, postprocedural infections occurred in 1.6% (95) of patients, a rate that mirrors that of the general population, Dr. Nguyen noted. No significant differences in surgical site infection rates were observed between immunocompromised patients (2.1%, n = 15) and those who were immunocompetent (1.6%, n = 80; P = .30).

Importantly, among those who were immunocompromised, the rates of infection were not significantly different between those who did receive antibiotics (3.0%, n = 8) and those who did not receive antibiotics (1.5%, n = 7; P = .19).

The lack of a difference in surgical site infection rates among those who did and those who did not receive antibiotics extended to the entire study population (2.0% vs. 1.4%; P = .12).

The study cohort mainly comprised immunosuppressed transplant patients, notably, heart, lung, and kidney transplant patients. However, “even in this population, we did not see a higher rate of infection,” senior author Nima M. Gharavi, MD, PhD, director of dermatologic surgery and Mohs micrographic surgery and associate professor of medicine and pathology and laboratory medicine at Cedars-Sinai Medical Center, said in an interview.

Dr. Nima M. Gharavi

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

As increasing numbers of patients in their 80s, 90s, and even 100s present for possible Mohs micrographic surgery, surgeons are confronted with deciding when the risks of treatment may outweigh the benefits.

In one of two presentations at the annual meeting of the American College of Mohs Surgery that addressed this topic, Howard W. Rogers, MD, of Advanced Dermatology in Norwich, Conn., said that the crux of the issue is the concern not to undertreat. He noted that reduced access to dermatologic care during the pandemic has provided a stark lesson in the risks of delaying treatment in all age groups. “Mohs surgeons have all seen the consequences of delayed treatment due to the pandemic with enormous, destructive, and sometimes fatal cancers coming to the office in the last year,” he told this news organization.

“Pandemic-related treatment delay has caused increased suffering and morbidity for countless skin cancer patients across the U.S.,” he said. “In general, not treating skin cancer and hoping it’s not going to grow or having significant delays in treatment are a recipe for disastrous outcomes.”

That said, active monitoring may be appropriate “for select small cancers that tend to grow slowly in the very elderly,” added Dr. Rogers, the incoming ACMS president. Among the key situations where the benefits of active monitoring may outweigh the risks of surgery are small, slowly growing cancers, when frailty is an issue.

Frailty has been equated to compromised functionality, which can increase the risk of an array of complications, including prolonged wound healing and secondary complications stemming from immobility. The toll those issues can take on patients’ quality of life can be considerable, Dr. Rogers said.

When weighing treatment options with elderly patients, he emphasized that careful consideration should be given to whether the “time needed to benefit from a Mohs procedure is longer than the patient’s life expectancy.” Furthermore, a decision not to treat does not have to be the last word. “We need to have an honest dialogue on the consequences of nontreatment, but part of that should be that just because we don’t treat today, doesn’t mean we can’t treat it tomorrow, if necessary.”

Of note, he added, “more than 100,00 patients have surgery for basal cell carcinoma [BCC] in their last year of life.” And that figure will likely rise exponentially if population projections come to fruition, considering that the population of people over the age of 85 is predicted to increase to nearly 18 million in 2050, from 5.8 million in 2012, Dr. Rogers said.

Until more research emerges on how to best treat this age group, Dr. Rogers noted that experts recommend that for elderly patients, “treatment should be individualized with consideration of active monitoring of primary BCC that is not in the H-zone, asymptomatic, smaller than 1 cm, with treatment initiated if there is substantial growth or symptoms.” Ultimately, he urged surgeons to “be sensitive and treat our patients like ourselves or our family members.”
 

When appropriate – Mohs is safe in the very elderly

Taking on the issue in a separate presentation, Deborah MacFarlane, MD, professor of dermatology and head and neck surgery at MD Anderson Cancer Center, Houston, said that for skin cancer cases that warrant treatment, clinicians should not let age alone stand in the way of Mohs surgery.

The evidence of its safety in the elderly dates back to a paper published in 1997 that Dr. MacFarlane coauthored, describing Mohs surgery of BCCs, squamous cell cancers (SCCs), and melanomas among 115 patients aged 90 and older (average, 92.4 years) who had an average of 1.9 comorbid medical conditions, and were taking an average of 2.3 medications. “Overall, we had just one complication among the patients,” she said.

In a subsequent paper, Dr. MacFarlane and her colleagues found that age at the time of Mohs surgery, even in older patients, was unrelated to survival, stage of cancer, or the type of repair. “We have concluded that this rapidly growing segment of the population can undergo Mohs surgery and should not be relegated to less effective treatment out of fear of its affecting their survival,” Dr. MacFarlane said.

She agreed with the concern about frailty and hence functionality, which may need to be factored in when making a decision to perform Mohs surgery. “I think this is something we do intuitively anyway,” she added. “We’re going to offer Mohs to someone who we think will survive and who is in relatively good health,” Dr. MacFarlane noted.

The point is illustrated in a new multicenter study of 1,181 patients at 22 U.S. sites, aged 85 years and older with nonmelanoma skin cancer referred for Mohs surgery. In the study, published in JAMA Dermatology after the ACMS meeting, patients who had Mohs surgery were almost four times more likely to have high functional status (P < .001) and were more likely to have facial tumors (P < .001), compared with those who had an alternate surgery.

The main reasons provided by the surgeons for opting to treat with Mohs included a patient’s desire for treatment with a high cure rate (66%), good/excellent patient functional status for age (57%), and a high risk associated with the tumor based on histology (40%), noted Dr. MacFarlane, one of the authors.

She reiterated the point raised by Dr. Rogers that “this is something we’re going to increasingly face,” noting that people over 85 represent the fastest growing segment of the population. “I have more patients over the age of 100 than I’ve ever had before,” she said.

Nevertheless, her own experience with elderly patients speaks to the safety of Mohs surgery in this population: Dr. MacFarlane reported a review of her practice’s records of 171 patients aged 85 years and older between May 2016 and May 2022, who received 414 separate procedures, without a single complication.

Sharing many of Dr. Rogers’ concerns about using caution in at-risk patients, Dr. MacFarlane offered recommendations for the optimal treatment of elderly patients receiving Mohs, including handling tissue delicately, and “keep undermining to a minimum.” She noted that intermediate closures and full thickness skin grafts are ideal closures for the elderly, while flaps may be performed in selected robust skin. It is also important to involve caretakers from the onset, talk and listen to patients – and play their choice of music during treatment, she said.

Commenting on the debate, comoderator Nahid Y. Vidal, MD, of the department of dermatology, Mayo Clinic, Rochester, Minn., noted that the expanding older population is accompanied by increases in skin cancer, in addition to more immunosenescence that is related to development of infections, autoimmune disease, and malignant tumors.

“In our academic practice, as with both the reference speakers, we do frequently see elderly, and not uncommonly the super-elderly,” she told this news organization. “The take-home point for me is to treat your whole patient, not just the tumor,” considering social factors, frailty/spry factor, and preferences, “and to do the humanistic thing, while also remaining evidence based,” she said.

“Don’t assume that increased age translates to morbidity, worse outcomes, or futility of treatment,” she added. “Chances are, if [a patient] made it to 90 years old with only a few medications and few medical problems, they may make it to 100, so why put the patient at risk for metastasis and death from a treatable/curable skin cancer,” in the case of SCC, she said.

“By the same token, why not perform more conservative treatments such as ED&C [electrodesiccation and curettage] for very low-risk skin cancers in low-risk locations, such as a superficial basal cell carcinoma on the trunk?” Overall, instead of trying to determine how long a super-elderly individual will live, Dr. Vidal said that “it’s better to educate the patient, engage in a discussion about goals of care, and to make few assumptions.”

Dr. Rogers, Dr. MacFarlane, and Dr. Vidal report no disclosures.

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

Trauma surgeons are in the tough position of seeing victims just after gun violence across the United States, and they have some advice.

Their strategies can work regardless of where you stand on the Second Amendment of the Constitution, said Patricia Turner, MD. “Our proposals are embraced by both gun owners and non–gun owners alike, and we are unique in that regard.”

These “implementable solutions” could prevent the next massacre, Dr. Turner, executive director of the American College of Surgeons, said during a news briefing the group sponsored on June 2.

“Our future – indeed all of our futures – depend on our ability to find durable, actionable steps that we can implement tomorrow to save lives,” she said.
 

Firsthand perspective

“Sadly I’m here today as a trauma surgeon who has cared for two of the largest mass shootings in modern U.S. history,” said Ronald Stewart, MD, chair of the department of surgery at University Hospital in San Antonio, Texas.

Dr. Stewart treated victims of the 2017 Sutherland Springs First Baptist Church shooting – where 27 people died, including the shooter – and the recent Uvalde school shooting, both in Texas.

“The injuries inflicted by high-velocity weapons used at both of these attacks are horrific. A high-capacity, magazine-fed automatic rifle such as the AR-15 causes extremely destructive tissue wounds,” he said.

One of the group’s proposals is to increase the regulation of high-velocity weapons, including AR-15s.

“These wounds are horribly lethal at close range, and sadly, most victims do not survive long enough to make it to a trauma center,” Dr. Stewart said.

On a positive note, “all of our current [Uvalde] patients are improving, which really brings us joy in this dark time,” he said. “But all of them have a long road to deal with recovery with both the physical and emotional impact of their injuries.”

Jeffrey Kerby, MD, agreed.

“Trauma surgeons see the short-term physical effects of these injuries and watch patients struggle with the long-term impact of these wounds,” said Dr. Kerby, director of trauma and acute care surgery at the University of Alabama at Birmingham.
 

Surgeons feel ‘profound impact’ of shootings

“Firearm violence has a profound impact on surgeons, and we are the undisputed subject matter experts in treating the tragic results,” said Patrick Bailey, MD, medical director for advocacy at the American College of Surgeons.

“This impacts surgeons as well,” said Dr. Kerby, chair of the Committee on Trauma for the surgeons’ group. “We are human, and we can’t help but share in the grief, the pain, and the suffering that our patients endure.

“As a pediatric surgeon ... I have too often witnessed the impact of firearm violence, and obviously, the devastation extends beyond the victims to their families,” he said. “To put it succinctly, in our culture, parents are not supposed to be put in a position of burying their children.”
 

A public health crisis

“It’s important to recognize that we’ve been talking about a public health approach,” said Eileen Bulger, MD, acting chief of the trauma division at the University of Washington in Seattle. That strategy is important for engaging both firearm owners and communities that have a higher risk for firearm violence, she said.

A committee of the American College of Surgeons developed specific recommendations in 2018, which are still valid today. The group brought together surgeons from across the U.S. including “passionate firearm owners and experts in firearm safety,” Dr. Bulger said.

The committee, for example, agreed on 10 specific recommendations “that we believe are bipartisan and could have an immediate impact in saving lives.”

“I’m a lifelong gun owner,” Dr. Bailey said, emphasizing that the team’s process included participation and perspective from other surgeons “who, like me, are also gun owners, but gun owners who also seek to reduce the impact of firearm violence in our country.”

The recommendations address these areas:

• Gun ownership
• Firearm registration
• Licensure
• Education and training
• Ownership responsibilities
• Mandatory reporting and risk reduction
• Safety innovation and technology
• Research
• The culture of violence
• Social isolation and mental health

For example, “we currently have certain classes of weapons with significant offensive capability,” Dr. Bulger said, “that are appropriately restricted and regulated under the National Firearms Act as Class 3 weapons.”

This group includes fully automatic machine guns, explosive devices, and short-barrel shotguns.

“We recommend a formal reassessment of the firearms designated within each of these national firearms classifications,” Dr. Bulger said.

For example, high-capacity, magazine-fed semiautomatic rifles, such as the AR-15, should be considered for reclassification as NFA Class 3 firearms, or they should get a new designation with tighter regulation.

The ACS endorses formal firearm safety training for all new gun owners. Also, owners who do not provide reasonably safe firearm storage should be held responsible for events related to the discharge of their firearms, Dr. Bulger said. And people who are deemed an imminent threat to themselves or others through firearm ownership should be temporarily or permanently restricted, with due process.
 

Research and reporting reforms

The ACS is also calling for research on firearm injuries and firearm injury prevention to be federally funded, Dr. Bulger said. The research should be done in a nonpartisan manner, she said.

“We have concerns that the manner and tone in which information is released to the public may lead to copycat mass killers,” she said. “The ACS recommends that law enforcement officials and the press take steps to eliminate the notoriety of the shooter, for example.”

Dr. Bulger also addressed the mental health angle. “We encourage recognition of mental health warning signs and social isolation by teachers, counselors, peers, and parents.” When identified, immediate referral to professionals is needed.

In addition to these recommendations, another team from the American College of Surgeons has published an overview of ways to address the inequities that contribute to violence. “We advocate for federal funding to support the development of hospital-based and community programs for violence intervention and prevention,” Dr. Bulger said.

Dr. Bailey said that as a gun owner himself, he thinks other gun owners would support these recommendations.

“I do not believe that the steps recommended ... pose undue burden on the rights of individual gun owners,” he said.
 

The time is now

Most firearm injuries are not from mass shooting events, Dr. Kerby said.

“My own trauma center has seen a 40% increase in the number of firearm injuries just in the last 2 years,” he added, “and these numbers continue to grow.”

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

Scientists have confirmed that a receptor long suspected to be linked to lupus is, in fact, a major driver of the autoimmune disease for at least some subset of patients, according to a study recently published in Nature. Researchers discovered the crucial role of toll-like receptor 7 (TLR7) because of a rare mutation in a pediatric patient with systemic lupus erythematosus (SLE) who had a particularly severe presentation.

“Sometimes it’s valuable to find these very severe cases where there is one mutation that has a strong effect because if we understand how those mutations work, the lessons we learn can generally tell us about disease mechanisms,” explained senior author Carola G. Vinuesa, MD, PhD, of the Centre for Personalised Immunology at Australian National University in Canberra and The Francis Crick Institute in London.

courtesy Michael Bowles

“It’s quite difficult to find one mutation that can alone cause the entire disease,” Dr. Vinuesa added, but what it reveals about how the disease develops may lead to more effective targeted therapies than the immune suppressants most often used to treat lupus currently.

The mutation they found was in the TLR7 gene that encodes the TLR7 protein. TLR7 is a receptor used by immune cells to identify viral RNA so they can fight off viral infections, including COVID-19. But if the body’s own genetic material binds to TLR7 in susceptible individuals, it can lead to an overproduction of type 1 interferons, which are cytokines that trigger or exacerbate the immune reactions that lead to lupus symptoms. The TLR7 gene occurs on the X chromosome, which may explain men’s greater susceptibility to COVID-19 and the greater incidence of lupus in women, who have two X chromosomes instead of the one that men have, Dr. Vinuesa said.

Previous research had shown an association between TLR7 and lupus, but this new study is the first to provide definitive proof that a TLR7 mutation by itself can directly cause human lupus. After discovering the variant in the patient, Dr. Vinuesa’s team used CRISPR to edit the genome of a mouse model and introduce the same mutation the patient had. “And they developed full-blown disease, just with this one single base-pair substitution – 1 letter in the 3 billion letters of the genome,” Dr. Vinuesa said. “It tells us that these receptors are not just there to recognize viral RNA, that in some circumstances, they could be triggered by our own nucleic acids.”
 

One pathway among many?

The finding does not mean that every lupus patient has this mutation, which remains rare, but suggests that overactivity in this receptor already reported in many lupus patients may be causally related to disease, Dr. Vinuesa said.

Noa Schwartz, MD, an assistant professor of medicine at Albert Einstein College of Medicine, New York, and director of the Montefiore-Einstein Institute for Lupus Care and Research, said in an interview that lupus is thought of as a syndrome, a collection of different but similar diseases that don’t necessarily have a single cause. But finding a single gene mutation that could potentially lead to lupus is an important piece of the puzzle, said Dr. Schwartz, who was not involved in the study. Based on past research in mice models, “we’ve hypothesized that TLR7 is important in humans as well, but this is the last nail in the coffin.”

One of the key questions this finding has prompted is how many patients’ disease results from TLR7 activity. “Because of the evidence from Ignacio Sanz’s group demonstrating TLR7 overactivity in a significant fraction of SLE patients, we believe that it is probably going to be pretty important,” Dr. Vinuesa said. “My feeling is that it is going to be quite a central pathway in lupus pathogenesis, if not the central pathway.”

Dr. Schwartz was more cautious, noting that it is probably important for a subset of patients but may “have a limited effect on the general lupus population.” While it’s not yet clear how large that subset is, it is possible it will include people with cutaneous lupus, those with primarily dermatologic symptoms.

“Hydroxychloroquine works particularly well for cutaneous manifestations of lupus, and one of the ways that works is by inhibiting TLR7 and TLR9, so this [finding] potentially matters for skin disease and lupus, but it’s very early,” Dr. Schwartz said. If it does turn out that TLR7 activity is particularly associated with cutaneous lupus, it may mean therapies with fewer side effects, she said. “Specifically for cutaneous lupus, the concept of suppressing the entire immune system for skin illness sometimes feels, especially to patients, very extreme, so they are [patients] who directed therapy could be so especially relevant for.”

Laura Lewandowski, MD, an assistant clinical investigator and head of the lupus genomics and global health disparities unit at the National Institute of Arthritis and Musculoskeletal and Skin Disease, described this study as particularly remarkable in the way it revealed the mechanism leading to lupus symptoms.

“As whole genome sequencing becomes faster and less expensive, more and more people are employing them in their studies,” most of which report changes in certain genes, Dr. Lewandowski said. “One of the most striking findings about this paper was that they took it to the next step and did a really elegant study on the exact way this gain-of-function TLR7 mutation leads to the autoimmunity that we see in lupus. The detail of mechanism in this paper is really unique.”
 

A step toward personalized medicine

Dr. Lewandowski is part of a team that recently presented a poster related to genomic sequencing in lupus patients at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance. Her study reported on the whole genome sequencing of patients with childhood-onset SLE who were already enrolled in the CARRA Lupus Registry. Children with lupus may be more likely than adults to have rare genetic variants, so a registry of childhood-onset SLE patients with fully sequenced genomes provides an opportunity to look for single-gene mutations specifically linked to lupus, said Dr. Lewandowski, who has recently begun a research collaboration with Dr. Vinuesa.

“As we move forward and more and more patients are included in these studies, we will understand a little bit more about the genetic architecture of patients who have rare variations leading to disease, or even common variations,” Dr. Lewandowski said about the intersection between her research and Dr. Vinuesa’s study. The more data they gather, the more they can explore the possible interactions of rare and common variants that play a role in SLE as well as what environmental triggers, such as viral infection or pollution exposure, might tip someone into having an autoimmune disease. “We’re just starting to peek under the hood,” Dr. Lewandowski said.

If further research can reveal the relative contribution of genetics to the disease and what those genetic drivers are, it may allow for greater precision in therapies and “ultimately improve the quality of life for our patients, the ultimate goal of all of these studies,” Dr. Lewandowski said.

Drugs that target TLR7 already exist for other indications, and clinical trials have already begun to see if these TLR7 inhibitors benefit lupus patients.

“If the clinical trials work, this will be quite a nice, targeted therapy with potentially much less side effects than other therapies on the market at the moment,” Dr. Vinuesa said. She is cautiously hopeful, saying it’s likely to make an impact on lupus treatment, but it’s too early to say precisely how much.

“It allows us to understand the disease mechanisms a little bit better and to try and assess what percentage of patients’ disease can be explained by overactivity in this receptor,” Dr. Vinuesa said. She thinks it’s possible that TLR7 over activation may be relevant to other systemic autoimmune diseases as well, such as Sjögren’s syndrome, rheumatoid arthritis, or juvenile dermatomyositis, but it will take more studies to find out.

“Right now, we have medicines that broadly inhibit the immune system and aren’t as targeted, but we have a lot more clinical and scientific work to do before we move this field forward for lupus patients,” Dr. Lewandowski said. “This is one case where they were able to find the exact molecular defect, and it’s not the end of the path of precision medicine — it’s the beginning.”

Dr. Vinuesa, Dr. Schwartz, and Dr. Lewandowski reported no disclosures.

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

Scientists have confirmed that a receptor long suspected to be linked to lupus is, in fact, a major driver of the autoimmune disease for at least some subset of patients, according to a study recently published in Nature. Researchers discovered the crucial role of toll-like receptor 7 (TLR7) because of a rare mutation in a pediatric patient with systemic lupus erythematosus (SLE) who had a particularly severe presentation.

“Sometimes it’s valuable to find these very severe cases where there is one mutation that has a strong effect because if we understand how those mutations work, the lessons we learn can generally tell us about disease mechanisms,” explained senior author Carola G. Vinuesa, MD, PhD, of the Centre for Personalised Immunology at Australian National University in Canberra and The Francis Crick Institute in London.

courtesy Michael Bowles

“It’s quite difficult to find one mutation that can alone cause the entire disease,” Dr. Vinuesa added, but what it reveals about how the disease develops may lead to more effective targeted therapies than the immune suppressants most often used to treat lupus currently.

The mutation they found was in the TLR7 gene that encodes the TLR7 protein. TLR7 is a receptor used by immune cells to identify viral RNA so they can fight off viral infections, including COVID-19. But if the body’s own genetic material binds to TLR7 in susceptible individuals, it can lead to an overproduction of type 1 interferons, which are cytokines that trigger or exacerbate the immune reactions that lead to lupus symptoms. The TLR7 gene occurs on the X chromosome, which may explain men’s greater susceptibility to COVID-19 and the greater incidence of lupus in women, who have two X chromosomes instead of the one that men have, Dr. Vinuesa said.

Previous research had shown an association between TLR7 and lupus, but this new study is the first to provide definitive proof that a TLR7 mutation by itself can directly cause human lupus. After discovering the variant in the patient, Dr. Vinuesa’s team used CRISPR to edit the genome of a mouse model and introduce the same mutation the patient had. “And they developed full-blown disease, just with this one single base-pair substitution – 1 letter in the 3 billion letters of the genome,” Dr. Vinuesa said. “It tells us that these receptors are not just there to recognize viral RNA, that in some circumstances, they could be triggered by our own nucleic acids.”
 

One pathway among many?

The finding does not mean that every lupus patient has this mutation, which remains rare, but suggests that overactivity in this receptor already reported in many lupus patients may be causally related to disease, Dr. Vinuesa said.

Noa Schwartz, MD, an assistant professor of medicine at Albert Einstein College of Medicine, New York, and director of the Montefiore-Einstein Institute for Lupus Care and Research, said in an interview that lupus is thought of as a syndrome, a collection of different but similar diseases that don’t necessarily have a single cause. But finding a single gene mutation that could potentially lead to lupus is an important piece of the puzzle, said Dr. Schwartz, who was not involved in the study. Based on past research in mice models, “we’ve hypothesized that TLR7 is important in humans as well, but this is the last nail in the coffin.”

One of the key questions this finding has prompted is how many patients’ disease results from TLR7 activity. “Because of the evidence from Ignacio Sanz’s group demonstrating TLR7 overactivity in a significant fraction of SLE patients, we believe that it is probably going to be pretty important,” Dr. Vinuesa said. “My feeling is that it is going to be quite a central pathway in lupus pathogenesis, if not the central pathway.”

Dr. Schwartz was more cautious, noting that it is probably important for a subset of patients but may “have a limited effect on the general lupus population.” While it’s not yet clear how large that subset is, it is possible it will include people with cutaneous lupus, those with primarily dermatologic symptoms.

“Hydroxychloroquine works particularly well for cutaneous manifestations of lupus, and one of the ways that works is by inhibiting TLR7 and TLR9, so this [finding] potentially matters for skin disease and lupus, but it’s very early,” Dr. Schwartz said. If it does turn out that TLR7 activity is particularly associated with cutaneous lupus, it may mean therapies with fewer side effects, she said. “Specifically for cutaneous lupus, the concept of suppressing the entire immune system for skin illness sometimes feels, especially to patients, very extreme, so they are [patients] who directed therapy could be so especially relevant for.”

Laura Lewandowski, MD, an assistant clinical investigator and head of the lupus genomics and global health disparities unit at the National Institute of Arthritis and Musculoskeletal and Skin Disease, described this study as particularly remarkable in the way it revealed the mechanism leading to lupus symptoms.

“As whole genome sequencing becomes faster and less expensive, more and more people are employing them in their studies,” most of which report changes in certain genes, Dr. Lewandowski said. “One of the most striking findings about this paper was that they took it to the next step and did a really elegant study on the exact way this gain-of-function TLR7 mutation leads to the autoimmunity that we see in lupus. The detail of mechanism in this paper is really unique.”
 

A step toward personalized medicine

Dr. Lewandowski is part of a team that recently presented a poster related to genomic sequencing in lupus patients at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance. Her study reported on the whole genome sequencing of patients with childhood-onset SLE who were already enrolled in the CARRA Lupus Registry. Children with lupus may be more likely than adults to have rare genetic variants, so a registry of childhood-onset SLE patients with fully sequenced genomes provides an opportunity to look for single-gene mutations specifically linked to lupus, said Dr. Lewandowski, who has recently begun a research collaboration with Dr. Vinuesa.

“As we move forward and more and more patients are included in these studies, we will understand a little bit more about the genetic architecture of patients who have rare variations leading to disease, or even common variations,” Dr. Lewandowski said about the intersection between her research and Dr. Vinuesa’s study. The more data they gather, the more they can explore the possible interactions of rare and common variants that play a role in SLE as well as what environmental triggers, such as viral infection or pollution exposure, might tip someone into having an autoimmune disease. “We’re just starting to peek under the hood,” Dr. Lewandowski said.

If further research can reveal the relative contribution of genetics to the disease and what those genetic drivers are, it may allow for greater precision in therapies and “ultimately improve the quality of life for our patients, the ultimate goal of all of these studies,” Dr. Lewandowski said.

Drugs that target TLR7 already exist for other indications, and clinical trials have already begun to see if these TLR7 inhibitors benefit lupus patients.

“If the clinical trials work, this will be quite a nice, targeted therapy with potentially much less side effects than other therapies on the market at the moment,” Dr. Vinuesa said. She is cautiously hopeful, saying it’s likely to make an impact on lupus treatment, but it’s too early to say precisely how much.

“It allows us to understand the disease mechanisms a little bit better and to try and assess what percentage of patients’ disease can be explained by overactivity in this receptor,” Dr. Vinuesa said. She thinks it’s possible that TLR7 over activation may be relevant to other systemic autoimmune diseases as well, such as Sjögren’s syndrome, rheumatoid arthritis, or juvenile dermatomyositis, but it will take more studies to find out.

“Right now, we have medicines that broadly inhibit the immune system and aren’t as targeted, but we have a lot more clinical and scientific work to do before we move this field forward for lupus patients,” Dr. Lewandowski said. “This is one case where they were able to find the exact molecular defect, and it’s not the end of the path of precision medicine — it’s the beginning.”

Dr. Vinuesa, Dr. Schwartz, and Dr. Lewandowski reported no disclosures.

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

Scientists have confirmed that a receptor long suspected to be linked to lupus is, in fact, a major driver of the autoimmune disease for at least some subset of patients, according to a study recently published in Nature. Researchers discovered the crucial role of toll-like receptor 7 (TLR7) because of a rare mutation in a pediatric patient with systemic lupus erythematosus (SLE) who had a particularly severe presentation.

“Sometimes it’s valuable to find these very severe cases where there is one mutation that has a strong effect because if we understand how those mutations work, the lessons we learn can generally tell us about disease mechanisms,” explained senior author Carola G. Vinuesa, MD, PhD, of the Centre for Personalised Immunology at Australian National University in Canberra and The Francis Crick Institute in London.

courtesy Michael Bowles

“It’s quite difficult to find one mutation that can alone cause the entire disease,” Dr. Vinuesa added, but what it reveals about how the disease develops may lead to more effective targeted therapies than the immune suppressants most often used to treat lupus currently.

The mutation they found was in the TLR7 gene that encodes the TLR7 protein. TLR7 is a receptor used by immune cells to identify viral RNA so they can fight off viral infections, including COVID-19. But if the body’s own genetic material binds to TLR7 in susceptible individuals, it can lead to an overproduction of type 1 interferons, which are cytokines that trigger or exacerbate the immune reactions that lead to lupus symptoms. The TLR7 gene occurs on the X chromosome, which may explain men’s greater susceptibility to COVID-19 and the greater incidence of lupus in women, who have two X chromosomes instead of the one that men have, Dr. Vinuesa said.

Previous research had shown an association between TLR7 and lupus, but this new study is the first to provide definitive proof that a TLR7 mutation by itself can directly cause human lupus. After discovering the variant in the patient, Dr. Vinuesa’s team used CRISPR to edit the genome of a mouse model and introduce the same mutation the patient had. “And they developed full-blown disease, just with this one single base-pair substitution – 1 letter in the 3 billion letters of the genome,” Dr. Vinuesa said. “It tells us that these receptors are not just there to recognize viral RNA, that in some circumstances, they could be triggered by our own nucleic acids.”
 

One pathway among many?

The finding does not mean that every lupus patient has this mutation, which remains rare, but suggests that overactivity in this receptor already reported in many lupus patients may be causally related to disease, Dr. Vinuesa said.

Noa Schwartz, MD, an assistant professor of medicine at Albert Einstein College of Medicine, New York, and director of the Montefiore-Einstein Institute for Lupus Care and Research, said in an interview that lupus is thought of as a syndrome, a collection of different but similar diseases that don’t necessarily have a single cause. But finding a single gene mutation that could potentially lead to lupus is an important piece of the puzzle, said Dr. Schwartz, who was not involved in the study. Based on past research in mice models, “we’ve hypothesized that TLR7 is important in humans as well, but this is the last nail in the coffin.”

One of the key questions this finding has prompted is how many patients’ disease results from TLR7 activity. “Because of the evidence from Ignacio Sanz’s group demonstrating TLR7 overactivity in a significant fraction of SLE patients, we believe that it is probably going to be pretty important,” Dr. Vinuesa said. “My feeling is that it is going to be quite a central pathway in lupus pathogenesis, if not the central pathway.”

Dr. Schwartz was more cautious, noting that it is probably important for a subset of patients but may “have a limited effect on the general lupus population.” While it’s not yet clear how large that subset is, it is possible it will include people with cutaneous lupus, those with primarily dermatologic symptoms.

“Hydroxychloroquine works particularly well for cutaneous manifestations of lupus, and one of the ways that works is by inhibiting TLR7 and TLR9, so this [finding] potentially matters for skin disease and lupus, but it’s very early,” Dr. Schwartz said. If it does turn out that TLR7 activity is particularly associated with cutaneous lupus, it may mean therapies with fewer side effects, she said. “Specifically for cutaneous lupus, the concept of suppressing the entire immune system for skin illness sometimes feels, especially to patients, very extreme, so they are [patients] who directed therapy could be so especially relevant for.”

Laura Lewandowski, MD, an assistant clinical investigator and head of the lupus genomics and global health disparities unit at the National Institute of Arthritis and Musculoskeletal and Skin Disease, described this study as particularly remarkable in the way it revealed the mechanism leading to lupus symptoms.

“As whole genome sequencing becomes faster and less expensive, more and more people are employing them in their studies,” most of which report changes in certain genes, Dr. Lewandowski said. “One of the most striking findings about this paper was that they took it to the next step and did a really elegant study on the exact way this gain-of-function TLR7 mutation leads to the autoimmunity that we see in lupus. The detail of mechanism in this paper is really unique.”
 

A step toward personalized medicine

Dr. Lewandowski is part of a team that recently presented a poster related to genomic sequencing in lupus patients at the annual meeting of the Childhood Arthritis and Rheumatology Research Alliance. Her study reported on the whole genome sequencing of patients with childhood-onset SLE who were already enrolled in the CARRA Lupus Registry. Children with lupus may be more likely than adults to have rare genetic variants, so a registry of childhood-onset SLE patients with fully sequenced genomes provides an opportunity to look for single-gene mutations specifically linked to lupus, said Dr. Lewandowski, who has recently begun a research collaboration with Dr. Vinuesa.

“As we move forward and more and more patients are included in these studies, we will understand a little bit more about the genetic architecture of patients who have rare variations leading to disease, or even common variations,” Dr. Lewandowski said about the intersection between her research and Dr. Vinuesa’s study. The more data they gather, the more they can explore the possible interactions of rare and common variants that play a role in SLE as well as what environmental triggers, such as viral infection or pollution exposure, might tip someone into having an autoimmune disease. “We’re just starting to peek under the hood,” Dr. Lewandowski said.

If further research can reveal the relative contribution of genetics to the disease and what those genetic drivers are, it may allow for greater precision in therapies and “ultimately improve the quality of life for our patients, the ultimate goal of all of these studies,” Dr. Lewandowski said.

Drugs that target TLR7 already exist for other indications, and clinical trials have already begun to see if these TLR7 inhibitors benefit lupus patients.

“If the clinical trials work, this will be quite a nice, targeted therapy with potentially much less side effects than other therapies on the market at the moment,” Dr. Vinuesa said. She is cautiously hopeful, saying it’s likely to make an impact on lupus treatment, but it’s too early to say precisely how much.

“It allows us to understand the disease mechanisms a little bit better and to try and assess what percentage of patients’ disease can be explained by overactivity in this receptor,” Dr. Vinuesa said. She thinks it’s possible that TLR7 over activation may be relevant to other systemic autoimmune diseases as well, such as Sjögren’s syndrome, rheumatoid arthritis, or juvenile dermatomyositis, but it will take more studies to find out.

“Right now, we have medicines that broadly inhibit the immune system and aren’t as targeted, but we have a lot more clinical and scientific work to do before we move this field forward for lupus patients,” Dr. Lewandowski said. “This is one case where they were able to find the exact molecular defect, and it’s not the end of the path of precision medicine — it’s the beginning.”

Dr. Vinuesa, Dr. Schwartz, and Dr. Lewandowski reported no disclosures.

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

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

SAN DIEGO – Twelve years ago, Merete Haedersdal, MD, PhD, and colleagues published data from a swine study, which showed for the first time that the ablative fractional laser can be used to boost the uptake of drugs into the skin.

That discovery paved the way for what are now well-established clinical applications of laser-assisted drug delivery for treating actinic keratoses and scars. According to Dr. Haedersdal, professor of dermatology at the University of Copenhagen, evolving clinical indications for laser-assisted drug delivery include rejuvenation, local anesthesia, melasma, onychomycosis, hyperhidrosis, alopecia, and vitiligo, while emerging indications include treatment of skin cancer with PD-1 inhibitors and combination chemotherapy regimens, and vaccinations.

During a presentation at the annual conference of the American Society for Laser Medicine and Surgery, she said that researchers have much to learn about laser-assisted drug delivery, including biodistribution of the drug being delivered. Pointing out that so far, “what we have been dealing with is primarily looking at the skin as a black box,” she asked, “what happens when we drill the holes and drugs are applied on top of the skin and swim through the tiny channels?”

By using high-performance liquid chromatography (HPLC) and HPLC mass spectrometry to measure drug concentration in the skin, she and her colleagues have observed enhanced uptake of drugs – 4-fold to 40-fold greater – primarily in ex vivo pig skin. “We do know from ex vivo models that it’s much easier to boost the uptake in the skin” when compared with in vivo human use, where much lower drug concentrations are detected, said Dr. Haedersdal, who, along with Emily Wenande, MD, PhD, and R. Rox Anderson, MD, at the Wellman Center for Photomedicine, at Massachusetts General Hospital, Boston, authored a clinical review, published in 2020, on the basics of laser-assisted drug delivery.

“What we are working on now is visualizing what’s taking place when we apply the holes and the drugs in the skin. This is the key to tailoring laser-assisted uptake to specific dermatologic diseases being treated,” she said. To date, she and her colleagues have examined the interaction with tissue using different devices, including ex vivo confocal microscopy, to view the thermal response to ablative fractional laser and radiofrequency. “We want to take that to the next level and look at the drug biodistribution.”

Efforts are underway to compare the pattern of drug distribution with different modes of delivery, such as comparing ablative fractional laser to intradermal needle injection. “We are also working on pneumatic jet injection, which creates a focal drug distribution,” said Dr. Haedersdal, who is a visiting scientist at the Wellman Center. “In the future, we may take advantage of device-tailored biodistribution, depending on which clinical indication we are treating.”

Another important aspect to consider is drug retention in the skin. In a study presented as an abstract at the meeting, led by Dr. Wenande, she, Dr. Haedersdal, and colleagues used a pig model to evaluate the effect of three vasoregulative interventions on ablative fractional laser-assisted 5-fluororacil concentrations in in vivo skin. The three interventions were brimonidine 0.33% solution, epinephrine 10 mcg/mL gel, and a 595-nm pulsed dye laser (PDL) in designated treatment areas.

“What we learned from that was in the short term – 1-4 hours – the ablative fractional laser enhanced the uptake of 5-FU, but it was very transient,” with a twofold increased concentration of 5-FU, Dr. Haedersdal said. Over 48-72 hours, after PDL, there was “sustained enhancement of drug in the skin by three to four times,” she noted.

The synergy of systemic drugs with ablative fractional laser therapy is also being evaluated. In a mouse study led by Dr. Haedersdal’s colleague, senior researcher Uffe H. Olesen, PhD, the treatment of advanced squamous cell carcinoma tumors with a combination of ablative fractional laser and systemic treatment with PD-1 inhibitors resulted in the clearance of more tumors than with either treatment as monotherapy. “What we want to explore is the laser-induced tumor immune response in keratinocyte cancers,” she added.

“When you shine the laser on the skin, there is a robust increase of neutrophilic granulocytes.” Combining this topical immune-boosting response with systemic delivery of PD-1 inhibitors in a mouse model with basal cell carcinoma, she said, “we learned that, when we compare systemic PD-1 inhibitors alone to the laser alone and then with combination therapy, there was an increased tumor clearance of basal cell carcinomas and also enhanced survival of the mice” with the combination, she said. There were also “enhanced neutrophilic counts and both CD4- and CD8-positive cells were increased,” she added.

Dr. Haedersdal disclosed that she has received grants or research funding from Lutronic, Venus Concept, Leo Pharma, and Mirai Medical.

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

NEW ORLEANS – The COVID-19 pandemic has challenged the academic and psychological stability of medical students, leading to high rates of burnout.

Researchers surveyed 613 medical students representing all years of a medical program during the last week of the Spring semester of 2021.

Based on the Maslach Burnout Inventory-Student Survey (MBI-SS), more than half (54%) of the students had symptoms of burnout.

Eighty percent of students scored high on emotional exhaustion, 57% scored high on cynicism, and 36% scored low on academic effectiveness.

Compared with male medical students, female medical students were more apt to exhibit signs of burnout (60% vs. 44%), emotional exhaustion (80% vs. 73%), and cynicism (62% vs. 49%).

After adjusting for associated factors, female medical students were significantly more likely to suffer from burnout than male students (odds ratio, 1.90; 95% confidence interval, 1.34-2.70; P < .001).

Smoking was also linked to higher likelihood of burnout among medical students (OR, 2.12; 95% CI, 1.18-3.81; P < .05). The death of a family member from COVID-19 also put medical students at heightened risk for burnout (OR, 1.60; 95% CI, 1.08-2.36; P < .05).

The survey results were presented at the American Psychiatric Association (APA) Annual Meeting.

The findings point to the need to study burnout prevalence in universities and develop strategies to promote the mental health of future physicians, presenter Sofia Jezzini-Martínez, fourth-year medical student, Autonomous University of Nuevo Leon, Monterrey, Mexico, wrote in her conference abstract.

In related research presented at the APA meeting, researchers surveyed second-, third-, and fourth-year medical students from California during the pandemic.

Roughly 80% exhibited symptoms of anxiety and 68% exhibited depressive symptoms, of whom about 18% also reported having thoughts of suicide.

Yet only about half of the medical students exhibiting anxiety or depressive symptoms sought help from a mental health professional, and 20% reported using substances to cope with stress.

“Given that the pandemic is ongoing, we hope to draw attention to mental health needs of medical students and influence medical schools to direct appropriate and timely resources to this group,” presenter Sarthak Angal, MD, psychiatry resident, Kaiser Permanente San Jose Medical Center, California, wrote in his conference abstract.
 

Managing expectations

Weighing in on medical student burnout, Ihuoma Njoku, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, noted that, “particularly for women in multiple fields, including medicine, there’s a lot of burden placed on them.”

“Women are pulled in a lot of different directions and have increased demands, which may help explain their higher rate of burnout,” Dr. Njoku commented.

She noted that these surveys were conducted during the COVID-19 pandemic, “a period when students’ education experience was a lot different than what they expected and maybe what they wanted.”

Dr. Njoku noted that the challenges of the pandemic are particularly hard on fourth-year medical students.

“A big part of fourth year is applying to residency, and many were doing virtual interviews for residency. That makes it hard to really get an appreciation of the place you will spend the next three to eight years of your life,” she told this news organization.

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

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

SAN DIEGO – In a 2006 report of complications from laser dermatologic surgery, one of the authors, Dieter Manstein, MD, PhD, who had subjected his forearm to treatment with a fractional laser skin resurfacing prototype device, was included as 1 of the 19 featured cases.

Dr. Manstein, of the Cutaneous Biology Research Center in the department of dermatology at Massachusetts General Hospital, Boston, was exposed to three test spots in the evaluation of the effects of different microscopic thermal zone densities for the prototype device, emitting at 1,450 nm and an energy per MTZ of 3 mJ.

Two years later, hypopigmentation persisted at the test site treated with the highest MTZ density, while two other sites treated with the lower MTZ densities did not show any dyspigmentation. But he noticed something else during the experiment: He felt minimal to no pain as each test site was being treated.

“It took 7 minutes without any cooling or anesthesia,” Dr. Manstein recalled at the annual meeting of the American Society for Laser Medicine and Surgery. “It was not completely painless, but each time the laser was applied, sometimes I felt a little prick, sometimes I felt nothing.” Essentially, he added, “we created cell injury with a focused laser beam without anesthesia,” but this could also indicate that if skin is treated with a fractional laser very slowly, anesthesia is not needed. “Current devices are meant to treat very quickly, but if we [treat] slowly, maybe you could remove lesions painlessly without anesthesia.”

The observation from that experiment also led Dr. Manstein and colleagues to wonder: Could a focused laser beam pattern be used to assess cutaneous innervation? If so, they postulated, perhaps it could be used to not only assess nerve sensitivity of candidates for dermatologic surgery, but as a tool to help diagnose small fiber neuropathies such as diabetic neuropathy, and neuropathies in patients with HIV and sarcoidosis.

The current gold standard for making these diagnoses involves a skin biopsy, immunohistochemical analysis, and nerve fiber quantification, which is not widely available. It also requires strict histologic processing and nerve counting rules. Confocal microscopy of nerve fibers in the cornea is another approach, but is very difficult to perform, “so it would be nice if there was a simple way” to determine nerve fiber density in the skin using a focused laser beam, Dr. Manstein said.

With help from Payal Patel, MD, a dermatology research fellow at MGH, Dr. Manstein and colleagues have developed an intraepidermal nerve fiber density diagnostic device prototype that uses an erbium laser to conduct in vivo exposures, records each subject’s perception of a stimulus, and maps the areas of stimulus response. Current diameters being studied range from 0.076-1.15 mm and depths less than 0.71 mm. “We can focus the laser beam, preset the beam diameter, and very slowly, in a controlled manner, make a rectangular pattern, and after each time, inquire if the subject felt the pulse or not,” Dr. Manstein explained.

“This laser could become a new method for diagnosing nerve fiber neuropathies. If this works well, I think we can miniaturize the device,” he added.

Dr. Manstein disclosed that he is a consultant for Blossom Innovations, R2 Dermatology, and AVAVA. He is also a member of the advisory board for Blossom Innovations.

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

As the number of people reporting persistent, and sometimes debilitating, symptoms from COVID-19 increases, researchers have struggled to pinpoint exactly how common so-called “long COVID” is, as well as how to clearly define exactly who has it or who is likely to get it.

Now, Centers for Disease Control and Prevention researchers have concluded that one in five adults aged 18 and older have at least one health condition that might be related to their previous COVID-19 illness; that number goes up to one in four among those 65 and older. Their data was published in the CDC’s Morbidity and Mortality Weekly Report.

The conditions associated with what’s been officially termed postacute sequelae of COVID-19, or PASC, include kidney failure, blood clots, other vascular issues, respiratory issues, heart problems, mental health or neurologic problems, and musculoskeletal conditions. But none of those conditions is unique to long COVID.

Another new study, published in The Lancet Digital Health, is trying to help better characterize what long COVID is, and what it isn’t.

The research team, supported by the National Institutes of Health, used machine learning techniques to analyze electronic health record data to identify new information about long COVID and detect patterns that could help identify those likely to develop it.
 

CDC data

The CDC team came to its conclusions by evaluating the EHRs of more than 353,000 adults who were diagnosed with COVID-19 or got a positive test result, then comparing those records with 1.6 million patients who had a medical visit in the same month without a positive test result or a COVID-19 diagnosis.

They looked at data from March 2020 to November 2021, tagging 26 conditions often linked to post-COVID issues.

Overall, more than 38% of the COVID patients and 16% of those without COVID had at least one of these 26 conditions. They assessed the absolute risk difference between the patients and the non-COVID patients who developed one of the conditions, finding a 20.8–percentage point difference for those 18-64, yielding the one in five figure, and a 26.9–percentage point difference for those 65 and above, translating to about one in four.

“These findings suggest the need for increased awareness for post-COVID conditions so that improved post-COVID care and management of patients who survived COVID-19 can be developed and implemented,” said study author Lara Bull-Otterson, PhD, MPH, colead of data analytics at the Healthcare Data Advisory Unit of the CDC.
 

Pinpointing long COVID characteristics

Long COVID is difficult to identify, because many of its symptoms are similar to those of other conditions, so researchers are looking for better ways to characterize it to help improve both diagnosis and treatment.

Researchers on the Lancet study evaluated data from the National COVID Cohort Collaborative, N3C, a national NIH database that includes information from more than 8 million people. The team looked at the health records of 98,000 adult COVID patients and used that information, along with data from about nearly 600 long-COVID patients treated at three long-COVID clinics, to create three machine learning models for identifying long-COVID patients.

The models aimed to identify long-COVID patients in three groups: all patients, those hospitalized with COVID, and those with COVID but not hospitalized. The models were judged by the researchers to be accurate because those identified at risk for long COVID from the database were similar to those actually treated for long COVID at the clinics.

“Our algorithm is not intended to diagnose long COVID,” said lead author Emily Pfaff, PhD, research assistant professor of medicine at the University of North Carolina at Chapel Hill. “Rather, it is intended to identify patients in EHR data who ‘look like’ patients seen by physicians for long COVID.’’

Next, the researchers say, they will incorporate the new patterns they found with a diagnosis code for COVID and include it in the models to further test their accuracy. The models could also be used to help recruit patients for clinical trials, the researchers say.
 

Perspective and caveats

The figures of one in five and one in four found by the CDC researchers don’t surprise David Putrino, PT, PhD, director of rehabilitation innovation for Mount Sinai Health System in New York and director of its Abilities Research Center, which cares for long-COVID patients.

“Those numbers are high and it’s alarming,” he said. “But we’ve been sounding the alarm for quite some time, and we’ve been assuming that about one in five end up with long COVID.”

He does see a limitation to the CDC research – that some symptoms could have emerged later, and some in the control group could have had an undiagnosed COVID infection and gone on to develop long COVID.

As for machine learning, “this is something we need to approach with caution,” Dr. Putrino said. “There are a lot of variables we don’t understand about long COVID,’’ and that could result in spurious conclusions.

“Although I am supportive of this work going on, I am saying, ‘Scrutinize the tools with a grain of salt.’ Electronic records, Dr. Putrino points out, include information that the doctors enter, not what the patient says.

Dr. Pfaff responds: “It is entirely appropriate to approach both machine learning and EHR data with relevant caveats in mind. There are many clinical factors that are not recorded in the EHR, and the EHR is not representative of all persons with long COVID.” Those data can only reflect those who seek care for a condition, a natural limitation.

When it comes to algorithms, they are limited by data they have access to, such as the electronic health records in this research. However, the immense size and diversity in the data used “does allow us to make some assertations with much more confidence than if we were using data from a single or small number of health care systems,” she said.

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

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Monitoring serum brodalumab levels may help doctors treat some patients with psoriasis more effectively, the authors of a small Danish case series report.

In a study of patients with psoriasis who had previously failed treatment with interleukin-17 receptor A inhibitor therapy, “all patients with quantifiable levels of brodalumab after 12 weeks of therapy experienced PASI reductions” and subquantifiable brodalumab levels were associated with a lack of response after 12 weeks, they wrote in JAMA Dermatology.

Lead study author Christian Enevold, PhD, a researcher at the Institute for Inflammation Research at Copenhagen University Hospital, and colleagues monitored patients with plaque psoriasis who had not improved with previous IL-17A inhibitor therapy, to evaluate whether trough levels and antidrug antibodies were associated with clinical response in this group of patients.

The 20 consecutive adult patients were treated at two academic hospital dermatology clinics between 2018 and 2020 and ranged in age from 19 to 66 years; 13 were male. At baseline, their weight ranged from 59 to 182 kg (median, 103 kg), their body mass index (BMI) ranged from 20 to 50 (median, 32), and their Psoriasis Area and Severity Index (PASI) scores ranged from 7 to 26 (median, 13). All had failed treatment with at least one IL-17A inhibitor, and 90% had failed treatment with at least one tumor necrosis factor–alpha or IL-12/-23 inhibitor.

Patients stopped taking systemic psoriasis therapies for 4 weeks before entering the study, then received subcutaneous injections of 210 mg of the IL-17A inhibitor brodalumab (Siliq) at weeks 0, 1, 2, and every 2 weeks thereafter. Patients whose PASI scores did not improve at least 75% from baseline (PASI 75) after 12 weeks of brodalumab discontinued treatment and left the study, while those who maintained PASI 75 were monitored for up to 52 weeks.

The researchers used assays to compare decreases in PASI score with brodalumab levels as well as with antibrodalumab antibodies at 12 weeks, and determined the following:

• Participants with quantifiable brodalumab levels (≥ 0.05 mcg/mL) showed a greater drop in PASI scores (median, 93%; range, 61%-100%) than those without quantifiable brodalumab levels (median, −3; range, −49% to 94%) (P = .006).
• Four of 5 patients (80%) who did not achieve a PASI 75, compared with 3 of 14 PASI 75 responders (21%), had drug levels too low to be measured (< 0.05 mcg/mL).
• The eight patients who did not have obesity (BMI < 30) had PASI reductions of at least 77%, and seven of the eight patients (88%) had quantifiable brodalumab levels.
• Six of the 12 patients with obesity (BMI ≥ 30) had brodalumab levels too low to be measured. Of those, four had increased PASI after 12 weeks of treatment. For all patients with obesity with quantifiable brodalumab levels, PASI scores dropped by at least 61% after 12 weeks.
• Five of the 12 (42%) patients with obesity versus 7 of the 8 (88%) patients without obesity had quantifiable brodalumab levels.
• None of the seven patients (35%) with subquantifiable drug levels after 12 weeks remained PASI responders.
• No antibrodalumab antibodies were detected in any serum samples.

The authors acknowledged that there were limitations of the study, including its retrospective design and restriction to the few available participants with a history of treatment failure.

Dr. Han

George Han, MD, PhD, associate professor of dermatology at Hofstra University, Hempstead, N.Y., said in an interview that he found the study interesting. “The authors did an admirable job looking at many factors to try to understand response to treatment in a challenging population of patients who had failed at least one, and in many cases, numerous, biologics from different classes.”

“The most interesting finding is that patients with higher BMIs had much higher rates of low-to-undetectable drug concentration,” said Dr. Han, who was not involved in the study. “This very practical finding could help patient care immediately. While it’s impractical to start performing assays of drug concentration in clinical practice, this finding certainly would guide my conversations with my heavier-set patients who have had multiple failures on previous biologics.

“I’m looking forward to further studies that explore this issue and provide better evidence-based guidance for treating patients who have experienced multi-biologic failure,” he added.

UC San Diego Health Sciences

Robert A. Dorschner, MD, assistant professor of dermatology at the UC San Diego Health System, also welcomed the study’s results.

“Current psoriasis treatment is based on trial-and-error application of various biologics targeting different pathways, with initial selection frequently based on insurance preference, not patient characteristics,” he said in an interview.

“Studies like this help clinicians make more informed decisions about whether a patient may benefit from a different dose or may require a different drug, and make those decisions earlier in therapy,” he said. “This can improve patient care and decrease costs associated with prolonged treatments with ineffective drugs.”

But Dr. Dorschner, who also was not involved in the study, cautions clinicians to not draw conclusions about dose adjustments from these results. “These findings need to be verified in a larger cohort,” he advised, “and they should drive future studies with larger cohorts and prospective designs.”

“The last couple of decades have seen an explosion in the availability of biologics targeting different cytokines, with significant benefits to patients,” Dr. Dorschner explained. “However, there is a dearth of information on how to choose the right biologic for a particular patient and how to assess the benefit of dose alteration versus changing the drug target. Medicine needs more studies like this one.”

Several authors of the study report financial relationships with LEO Pharma and other pharmaceutical companies. Most authors, including Dr. Enevold, reported no relevant financial relationships. Dr. Dorschner reported no relevant financial relationships. Dr. Han reported financial relationships with pharmaceutical companies not involved in the study. The study was funded by LEO Pharma and the Danish Biotechnology Program.
 

Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”

Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”

Doctor, doctor, gimme the news. I got a bad case of knowing better than you

Stop us if you’ve heard this before. One of your parents (let’s be honest, probably your ornery father) refuses to go to the doctor. You tell him it’s for the best, but in his words, “Doctors don’t know nothin’. I’m fine.” How many TV shows with grumpy fathers feature this exact plot in an episode as the frustrated child attempts increasingly convoluted traps to encourage the stubborn parent to get himself to the doctor?

rudall30/iStockphoto.com

As is so often the case, wacky sitcoms reflect reality, according to a new study from the Journal of the Economics of Aging. In a massive survey of 80,000 Europeans aged 50 years and older, the researchers found that individuals who were overconfident and rated their health as better than it actually was visited their doctor 17% less often than did those who correctly judge their own health. Fewer medical visits leaves them more vulnerable to chronic disease, since they’re not getting the preventive care they need to catch illnesses early.

Perhaps unsurprisingly, the inverse is also true: People who underestimate their health status visit the doctor 21% more often. On the one hand, regular visits to the doctor are a good thing, as is awareness of how healthy one really is. On the other hand, though, extra visits cost money and time, especially relevant in an aging society with high public health costs.

Nobody likes visiting the doctor, but it is kind of important, especially as we age and our bodies start to let us down. Confidence is fine, but don’t be overly confident. And if you do go, don’t be like a certain former president of the United States. Don’t pay a sycophant to look in your general direction and then declare that you are in very good (great!) condition on Twitter. That’s not how medicine is meant to work.
 

Your liver stays toddler age

Rapid cell regeneration might seem like something straight out of a sci-fi novel, but it happens to your liver all the time. So much so that the human liver is never a day over 3 years old.

Peter Gridley/Getty Images

How’s that possible? The liver deals with a lot of toxic substances in its job as the Brita filter of the human body, so it has a unique capacity among organs to regenerate itself after damage.

Dr. Olaf Bergmann and his team at Technical University Dresden’s (Germany) Center for Regenerative Therapies used retrospective radiocarbon birth dating to determine the age of the livers of a group of people who died at the ages of 20-84 years. The results were the same regardless of age.

This information could be a complete game changer for understanding cell regeneration. It’s important in determining cancer cell formation in the liver but also if new heart muscle cells can be generated in people with cardiovascular disease, which the researchers are looking into.

So sure, your liver may be totally capable of filtering those drinks at happy hour, but as old as it is, a juice box might be more appropriate.
 

To bee, or not to bee? That is the vacation

Sleeping is pretty important for humans, no doubt about that, so anything that improves sleep is worth considering, right? But how far would you go for a good night’s sleep? Would you be willing to travel to Italy to experience the ultimate white-noise generator?

Airbnb

For more on this exciting, yet also sleep-inducing, news story, let’s go to the village of Grottole in southern Italy, where we meet bee keeper and Airbnb host Rocco Filomeno. ”This is the first place in the world where you can sleep immersed in the distinctive sound and aroma of the bees, experiencing ‘bee-therapy’ in the most authentic and natural way,” he said in a written statement for Airbnb.

Mr. Filomeno worked with local NGO Wonder Grottole and a self-build specialist to take the next step in tiny-house evolution. The resulting structure cost just $17,000 – crowdfunded, of course, and built by 25 local bee-lievers (aka volunteers) – and consists of a single room surrounded by nine apiaries, which contain a combined total of 1 million working bees. It is now available to book on Airbnb, and guests “will receive their first lesson on bees and how to live with them,” Airbnb said.

The immersion in bee sound/scent is fully realized through the building’s most prominent interior feature, a screened box in the ceiling with a working hive that allows guests to see the bees and fall asleep to the “gently humming sound,” Airbnb explained. The sound from the hive is said to have a soothing effect that “acts as salve to day-to-day stressors,” according to the BBC.

This is just the start of a trend and we want in on it. Should our tiny house feature the sights/smells/sounds of angry rattlesnakes or a swarm of locusts?
 

Joysticks can make the world a better place

Someday, it might be possible for surgeons to treat a stroke or aneurysm during the “golden hour,” even if they’re not in the same hospital as the patient. MIT engineers have created a robotic system that can be controlled remotely with a modified joystick, so the patient can go to a closer, smaller hospital and be treated by a surgeon at a larger facility through live imaging.

Xuanhe Zhao et al/MIT

Endovascular surgery seems difficult enough with the patient and doctor in the same hospital, “but having a robot twist with the same level of sophistication [as a surgeon] is challenging,” Yoonho Kim, lead author of a study in Science Robotics, said in a written statement. “Our system is based on a fundamentally different mechanism.”

It involves “a medical-grade robotic arm with a magnet attached to its wrist. With a joystick and live imaging, an operator can adjust the magnet’s orientation and manipulate the arm to guide a soft and thin magnetic wire through arteries and vessels,” MIT explained in the statement.

The system was tested using life-like models, and it took each surgeon about an hour of training to learn how to use the new joystick and other equipment. Another perk: No exposure to radiation from x-ray imaging.

If someone you know is obsessed with video games, stop thinking “slacker” and start thinking “neurosurgeon.”