To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴

To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴

To the Editor:

One of the more common tick-borne infections seen in travelers returning from sub-Saharan Africa is caused by Rickettsia africae, which is the etiologic agent of African tick-bite fever (ATBF), the most common tick-borne bacterial zoonosis.¹ There are 2 known tick vectors of disease: Amblyomma variegatum, found in sub-Saharan Africa and the West Indies, and Amblyomma hebraeum, found specifically in southern Africa.^2,3

Unlike other disease-carrying ticks that passively wait on vegetation to be picked up by a host, A hebraeum uniquely attract other nearby ticks to the host. Studies have shown that male ticks feeding on a nonhuman host (usually cattle) can emit an aggression-attachment pheromone that attracts other ticks to the host. The presence of the pheromone allows unfed ticks to actively discriminate between hosts on which these parasites have fed successfully (ie, suitable hosts) and those on which they have not.⁴

The aggressive hunting nature of A hebraeum explains the clinical presentation of multiple eschars and why large groups of exposed travelers—such as soldiers, leisure safari tourists, game hunters, and foreign-aid workers—are affected.²

Another southern African spotted fever group, Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Ticks carrying R conorii exhibit a much less aggressive hunting stylethan A hebraeum; consequently, infected patients present with a single eschar site.⁵

Rickettsia africae is estimated to have very high prevalence (95.2%) in Amblyomma ticks and a fairly high prevalence (approximately 4.0% to 8.6%) in travelers coming from rural southern Africa,^6,7 with an incubation period of 5 to 10 days after inoculation by an infected tick.⁸ Signs include fever, a generalized maculopapular or papulovesicular rash, and regional lymphadenopathy; symptoms include fatigue, headache, and myalgia.

The inoculation eschar—single or multiple—commonly presents on the legs and is accompanied by tender lymphadenopathy of draining nodes^1,8 More severe findings, such as myocarditis and subacute neuropathy, have been reported in elderly patients.⁹

A 77-year-old man presented with a pruritic maculopapular and papulovesicular rash distributed over the upper and lower extremities of 3 weeks’ duration. The patient reported having been on a 12-day mission trip to Limpopo, South Africa, where he was constructing and installing safe toilets to replace dangerous toilet pits. He believed he had been bitten by 2 ticks, after which he noted a dark purple and black patch on the left lower leg by the third day of the trip. He developed a sudden persistent pruritic rash, first on the lower extremities and then spreading to the upper extremities. The patient was seen by an American physician in South Africa who gave him a 7-day course of oral doxycycline monohydrate 100 mg twice daily. He then returned to the United States.

Sixteen days after being bitten by the ticks, the patient was examined in our dermatology office. Physical examination revealed an erythematous plaque with a central eschar over the medial aspect of the left leg (Figure 1) and multiple 3- to 6-mm, erythematous, dome-shaped papules scattered over the dorsal aspects of the feet and ankles (Figure 2). The examination was otherwise normal. Blood was drawn the same day for laboratory analysis; no abnormalities of platelets, red blood cells, or white blood cells were found. Results of a chemistry panel and liver enzyme tests were within reference range.

Skin biopsies were taken to elucidate the underlying pathology. Although an arthropod assault was suspected, there also was concern for deep vessel vasculitis because of the presence of considerable petechiae and purpura (Figure 3). Histologically, leukocytoclasia was seen in deep dermal blood vessels. A mild eosinophilic spongiosis with a mixed dermal infiltrate was identified—strengthening our suspicion of an arthropod assault. Bacterial cultures for aerobes and anaerobes using material taken from the right shin showed no growth.

Ten days after the initial biopsies, serum specimens were drawn and swabs of eschar were collected and sent to the Centers for Disease Control and Prevention for further testing. Serum was tested by immunofluorescence assay (IFA) for spotted fever group IgG to detect Rocky Mountain spotted fever and ATBF antibodies; both tests were negative. Swab material from eschar was tested again by IFA for spotted fever group IgG (Rocky Mountain spotted fever) and antibodies to ATBF and with bacterial culture isolation and nucleic acid amplification; the culture and amplification came back positive for R africae.

Because the specialized tests confirmed infection with R africae, the patient was given triamcinolone cream 0.1% to apply twice daily to the pruritic lesions for as long as 4 weeks; an additional 14-day course of oral doxycycline monohydrate (100 mg twice daily) was given. At follow-up, the lesions had fully resolved without evident scarring.

Various diagnostic techniques can detect R africae. Bacterial culture and the polymerase chain reaction are specific and therefore diagnostic. In addition, the diagnosis of rickettsiosis can be made with serology testing, in which disease-specific antibodies are detected by indirect IFA using disease-specific antigens.

Antigens from R rickettsii (the agent of Rocky Mountain spotted fever), R conorii (Mediterranean spotted fever), and R africae (ATBF) are commercially available for making the diagnosis of rickettsiosis. However, antigens from R conorii exhibit cross-reactivity with R africae, which can confound the diagnosis.^1,10 Serologic IFA tests have been shown to be less sensitive, especially when performed after antibacterial treatment has started.

In a study, 17 of 65 (26%) ATBF-confirmed patients were seronegative (acute and convalescent-phase sera) against R africae; 14 had received doxycycline during the first week of clinical signs. The current hypothesis is that R africae is highly sensitive to doxycycline and that early exposure to the drug prevented development of detectable titers of reactive antibodies, thus producing a negative serology test.¹¹

Furthermore, it has been shown that seroconversion of IgG and IgM antibodies in R africae–infected sera is delayed compared to what is observed with R conorii–infected sera. Typically, seroconversion of R conorii–infected sera can be detected within 2 weeks; seroconversion in R africae–infected sera can take 4 weeks or longer.¹¹

Our patient had a confirmed case of ATBF secondary to R africae infection, which was evident from tissue culture isolation and polymerase chain reaction analysis of swab material obtained from eschar sites, both of which yielded a positive result for R africae. The traveler’s negative serologic status might be due to his early exposure to doxycycline or to the 4-week delay in R africae seroconversion; his serum was collected only 3 weeks after the tick bites.

Clinical signs also aid in making the diagnosis of ATBF and distinguishing R conorii from R africae infection. Because of the aggressive hunting nature of the tick carrying R africae, they are associated with multiple eschars and tend to affect groups of multiple people, especially in rural areas.^4,5 In contrast, ticks carrying R conorii yield a single eschar due to their passive style of infecting a host and because they favor a single host within urban areas.⁵ Both infections exhibit a maculopapular or papulovesicular rash and are accompanied by fatigue, headache, and myalgia, though ATBF tends to present with a milder rash than MSF.

Infection with either R conorii or R africae responds to tetracyclines, quinolones, and macrolides.^10,12

African tick-bite fever is becoming more common, which should encourage clinicians to become familiar with the disease. Less than 2 decades ago, ATBF virtually was unknown outside of Zimbabwe, Botswana, Tanzania, Zambia, and Kenya, where it is endemic. However, after the abolition of apartheid in the 1990s, international tourism in southern Africa increased 6-fold.¹³ African tick-bite fever is now one of the most common rickettsial infections in Africa.⁷ In addition to diagnosing ATBF and managing infected patients, clinicians can help prevent ATBF in individuals who travel to endemic areas by recommending commercial topical insect repellents containing at least 19.5% N,N-diethyl-meta-toluamide (DEET).¹⁴

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

There are millions of immature connections between the neurons in brains of adults that remain inactive until they’re recruited to help form new memories, according to neuroscientists from the Massachusetts Institute of Technology.

What to know:

• An estimated 30% of all synapses in the brain’s cortex are silent and become active to allow the adult brain to continually form new memories and leave existing conventional synapses unmodified.
• Silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened to allow the brain to remember new things.
• Using the silent synapses for the new memories does not overwrite the important memories stored in more mature synapses, which are harder to change.
• The brain’s neurons display a wide range of plasticity mechanisms that account for how brains can efficiently learn new things and retain them in long-term memory.
• Flexibility of synapses is critical for acquiring new information, and stability is required to retain important information, enabling one to more easily adjust and change behaviors and habits or incorporate new information.

This is a summary of the article, “Filopodia Are a Structural Substrate for Silent Synapses in Adult Neocortex,” published in Nature Nov. 30, 2022. The full article can be found at nature.com .

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

There are millions of immature connections between the neurons in brains of adults that remain inactive until they’re recruited to help form new memories, according to neuroscientists from the Massachusetts Institute of Technology.

What to know:

• An estimated 30% of all synapses in the brain’s cortex are silent and become active to allow the adult brain to continually form new memories and leave existing conventional synapses unmodified.
• Silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened to allow the brain to remember new things.
• Using the silent synapses for the new memories does not overwrite the important memories stored in more mature synapses, which are harder to change.
• The brain’s neurons display a wide range of plasticity mechanisms that account for how brains can efficiently learn new things and retain them in long-term memory.
• Flexibility of synapses is critical for acquiring new information, and stability is required to retain important information, enabling one to more easily adjust and change behaviors and habits or incorporate new information.

This is a summary of the article, “Filopodia Are a Structural Substrate for Silent Synapses in Adult Neocortex,” published in Nature Nov. 30, 2022. The full article can be found at nature.com .

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

There are millions of immature connections between the neurons in brains of adults that remain inactive until they’re recruited to help form new memories, according to neuroscientists from the Massachusetts Institute of Technology.

What to know:

• An estimated 30% of all synapses in the brain’s cortex are silent and become active to allow the adult brain to continually form new memories and leave existing conventional synapses unmodified.
• Silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened to allow the brain to remember new things.
• Using the silent synapses for the new memories does not overwrite the important memories stored in more mature synapses, which are harder to change.
• The brain’s neurons display a wide range of plasticity mechanisms that account for how brains can efficiently learn new things and retain them in long-term memory.
• Flexibility of synapses is critical for acquiring new information, and stability is required to retain important information, enabling one to more easily adjust and change behaviors and habits or incorporate new information.

This is a summary of the article, “Filopodia Are a Structural Substrate for Silent Synapses in Adult Neocortex,” published in Nature Nov. 30, 2022. The full article can be found at nature.com .

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

When New York oncologist Gabriel Sara, MD, approached the French actress and film director Emmanuelle Bercot after a screening of one of her films in Manhattan, he was thinking big.

He never dreamed she would think bigger.  

“I thought maybe she will do a movie about some of my beliefs,” he said.

“Ma’am, would you like to go in the trenches of cancer?” he asked her, inviting her to tour the oncology department at Mount Sinai West.

Whether it was the Lebanese-born doctor’s Parisian French, his gentle, double-handed handshake, or the perpetual twinkle in his eye, something convinced Ms. Bercot to go. After the visit, she decided to base an entire film on the doctor’s philosophy about death, and she even cast him as one of the leads.

With no formal training in acting, “it’s incredible and prodigious what he did,” Ms. Bercot said in an interview at the 2021 Cannes Film Festival, where the film, “Peaceful” (“De Son Vivant”) premiered.

“This is a guy we took from his cancer ward to a film set, and he was able to be as real and authentic as he is in his doctor’s office,” she said.

Dr. Sara said that authenticity came easily, given that “a lot of my dialogue – maybe most – came from things I shared with Emmanuelle,” he said in an interview with this news organization. “She took the information from me, and she created the whole story. She studied my character and came up with really all the messages that I was hoping to share.”

He said that acting alongside professionals was not intimidating once he realized he was simply playing himself. “At some point ... it clicked in my head. Let me stop acting – I should just be me,” he recalled.

“Peaceful,” performed in French with English subtitles, was nominated for Best Film at the 2022 Lumières Awards.

It tells the story of a 39-year-old man (played by French actor Benoît Magimel) diagnosed with stage 4 pancreatic cancer and the journey, along with his mother (played by renowned actress Catherine Deneuve), through diagnosis, denial, and eventual acceptance of his death.

It is also the story of an oncologist, played by Dr. Sara as himself, who takes his patient by the hand, and refuses to sugarcoat the truth, because he believes that it is only by facing the facts that patients can continue to live – and then die – in peace.

“You’ll never hear me say I’ll cure your cancer. I’d be a liar if I did,” he tells his patient in the film.

“Patients put their life in your hands, so if you don’t tell them the truth you are betraying them,” he explained in the interview. “I have refused to see patients whose family did not allow them to come to the consultation to hear the truth. ... Nobody hears the truth and feels great about it the next day, but the truth helps them focus on what they need to deal with. And once they focus, they’re in control ... a big part of what is terrible for patients is that loss of control.”

The approach may sound harsh, but it is conveyed tenderly in the film. “[Your mother] thinks that half-truths will hurt you half as much,” he tells his patient gently, but “the scariest thing is realizing someone is lying to you. ... We have a tough journey ahead, there’s no room for lies. ... For me, truth is nonnegotiable.”  

Dr. Sara is brimming with stories of real-life patients whose lives were enriched and empowered by the clarity they gained in knowing the full truth.

However, not all oncologists agree with his style.

After screenings of the film in other parts of the world, and even in the United States, he has encountered some physicians who strongly disagree with his uncompromising honesty. “You always have somebody who says you know, in America, you will receive the truth but not in our culture – people are not used to it. I hear this all the time,” he said.

“And a long time ago, I decided I’m not going to accept that conversation. Truth works with all patients across all cultures,” Dr. Sara insisted.

“However, as caregivers, we have to be sensitive and present to the kind of culture we are dealing with. The content has to be always 100% honest but we adapt our language to the cultural and emotional state of the patient in order to successfully transmit the message,” he added.

Helping patients digest the news of their diagnosis and prognosis has been Dr. Sara’s recipe for his own survival at work. Now 68 and recently retired as medical director of the chemotherapy infusion suite and executive director of the patient services initiative at Mount Sinai West, he says he emerged from 40 years of practice without burning out by learning to step in time with each patient.

“My recipe for it is tango,” he said. Regular tango performances on his cancer ward were among his many real-life techniques that Ms. Bercot incorporated into the film. “I feel that we have to dance closely with our patients’ emotion,” he explained. “We have to feel our patients’ emotion and work with that. If you don’t move in harmony with your partner, you trip together and both of you will fall,” he told an audience after a screening of his film in New York City.

“I completely try to isolate my mind from anything else in order to be with the patient – this is what presence is about for me – to be right there for them, close to them. To spend that whole moment with them. That’s what will make the consultation really helpful, and will make me feel that I can move to the next page without feeling exhausted from the first one.”

A key scene in the film comes after the patient’s mother is stunned to discover a cheerful tango performance on her son’s ward, and confronts the doctor angrily.

“It’s like I’m abandoning him,” she says tearfully, when the doctor urges her to accept that her son’s chemotherapy is no longer working and let him live what life he has left.

“Give him permission to go,” he urges her. “It would be your greatest gift of love.”

Dr. Sara encourages a similar approach in his staff. He warns them about the “hero syndrome,” in which dying patients are made to feel they need to “hang on” and “fight” for the sake of their caregivers and families.

“The patient never asked to be the hero, but our attitude is telling him that he’s the hero,” he says in the film. “That puts him in an intolerable impasse because he figures that if he gives up, if he dies, he’s betraying his fans. He needs the exact opposite: to be set free. He needs the permission to die. That permission is given by two people: his doctor and his family.”

Of course, not all cancer patients have such a dim prognosis, and Dr. Sara is the first to forge ahead if he feels it’s appropriate. “If, if there is no option for them, I’m going to be aggressive to protect them. But when there is a curable disease, I will go broke to try to treat my patient. I’m willing to give them toxic drugs and hold their hand, get them through the storm if I believe it’s going to cure what they have, and I will coach them to accept being sick.”

He also believes in physical contact with the patient. “If we have some intimacy with the patient, we can at least palpate the kind of person they are,” he said. But his wife Nada pointed out that physical examinations can sometimes make patients nervous. “She told me, if you have a tie, they might have fun looking at it.” Thus began Dr. Sara’s collection of about 30 fun ties decorated with unicorns or jellyfish tailored to various patients’ preferences.

In the film, his patient teases him about this quirk, but Dr. Sara insists it is a small gesture that carries meaning. “One patient told me a story about lovebugs. She would see them in her kitchen when she was feeling well – so lovebugs became a sign of hope for her. I was telling the story to my wife ... so she got me a tie with lovebugs on it, and my patient was so happy when she saw me wearing that.”

In the film – and in real life – Dr. Sara often played guitar at breakfast music sessions with his staff in which he encouraged them to express their feelings about patients’ struggles. “If you cry, don’t be ashamed. Your patient will feel you’re with him,” he said in the film. In the final scenes, wearing a cloud-covered tie, he says goodbye to his patient with tears in his eyes. “They [the tears] are sincere,” he recalled. “Because I really felt I was looking at a dying patient. I really did.”

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

When New York oncologist Gabriel Sara, MD, approached the French actress and film director Emmanuelle Bercot after a screening of one of her films in Manhattan, he was thinking big.

He never dreamed she would think bigger.  

“I thought maybe she will do a movie about some of my beliefs,” he said.

“Ma’am, would you like to go in the trenches of cancer?” he asked her, inviting her to tour the oncology department at Mount Sinai West.

Whether it was the Lebanese-born doctor’s Parisian French, his gentle, double-handed handshake, or the perpetual twinkle in his eye, something convinced Ms. Bercot to go. After the visit, she decided to base an entire film on the doctor’s philosophy about death, and she even cast him as one of the leads.

With no formal training in acting, “it’s incredible and prodigious what he did,” Ms. Bercot said in an interview at the 2021 Cannes Film Festival, where the film, “Peaceful” (“De Son Vivant”) premiered.

“This is a guy we took from his cancer ward to a film set, and he was able to be as real and authentic as he is in his doctor’s office,” she said.

Dr. Sara said that authenticity came easily, given that “a lot of my dialogue – maybe most – came from things I shared with Emmanuelle,” he said in an interview with this news organization. “She took the information from me, and she created the whole story. She studied my character and came up with really all the messages that I was hoping to share.”

He said that acting alongside professionals was not intimidating once he realized he was simply playing himself. “At some point ... it clicked in my head. Let me stop acting – I should just be me,” he recalled.

“Peaceful,” performed in French with English subtitles, was nominated for Best Film at the 2022 Lumières Awards.

It tells the story of a 39-year-old man (played by French actor Benoît Magimel) diagnosed with stage 4 pancreatic cancer and the journey, along with his mother (played by renowned actress Catherine Deneuve), through diagnosis, denial, and eventual acceptance of his death.

It is also the story of an oncologist, played by Dr. Sara as himself, who takes his patient by the hand, and refuses to sugarcoat the truth, because he believes that it is only by facing the facts that patients can continue to live – and then die – in peace.

“You’ll never hear me say I’ll cure your cancer. I’d be a liar if I did,” he tells his patient in the film.

“Patients put their life in your hands, so if you don’t tell them the truth you are betraying them,” he explained in the interview. “I have refused to see patients whose family did not allow them to come to the consultation to hear the truth. ... Nobody hears the truth and feels great about it the next day, but the truth helps them focus on what they need to deal with. And once they focus, they’re in control ... a big part of what is terrible for patients is that loss of control.”

The approach may sound harsh, but it is conveyed tenderly in the film. “[Your mother] thinks that half-truths will hurt you half as much,” he tells his patient gently, but “the scariest thing is realizing someone is lying to you. ... We have a tough journey ahead, there’s no room for lies. ... For me, truth is nonnegotiable.”  

Dr. Sara is brimming with stories of real-life patients whose lives were enriched and empowered by the clarity they gained in knowing the full truth.

However, not all oncologists agree with his style.

After screenings of the film in other parts of the world, and even in the United States, he has encountered some physicians who strongly disagree with his uncompromising honesty. “You always have somebody who says you know, in America, you will receive the truth but not in our culture – people are not used to it. I hear this all the time,” he said.

“And a long time ago, I decided I’m not going to accept that conversation. Truth works with all patients across all cultures,” Dr. Sara insisted.

“However, as caregivers, we have to be sensitive and present to the kind of culture we are dealing with. The content has to be always 100% honest but we adapt our language to the cultural and emotional state of the patient in order to successfully transmit the message,” he added.

Helping patients digest the news of their diagnosis and prognosis has been Dr. Sara’s recipe for his own survival at work. Now 68 and recently retired as medical director of the chemotherapy infusion suite and executive director of the patient services initiative at Mount Sinai West, he says he emerged from 40 years of practice without burning out by learning to step in time with each patient.

“My recipe for it is tango,” he said. Regular tango performances on his cancer ward were among his many real-life techniques that Ms. Bercot incorporated into the film. “I feel that we have to dance closely with our patients’ emotion,” he explained. “We have to feel our patients’ emotion and work with that. If you don’t move in harmony with your partner, you trip together and both of you will fall,” he told an audience after a screening of his film in New York City.

“I completely try to isolate my mind from anything else in order to be with the patient – this is what presence is about for me – to be right there for them, close to them. To spend that whole moment with them. That’s what will make the consultation really helpful, and will make me feel that I can move to the next page without feeling exhausted from the first one.”

A key scene in the film comes after the patient’s mother is stunned to discover a cheerful tango performance on her son’s ward, and confronts the doctor angrily.

“It’s like I’m abandoning him,” she says tearfully, when the doctor urges her to accept that her son’s chemotherapy is no longer working and let him live what life he has left.

“Give him permission to go,” he urges her. “It would be your greatest gift of love.”

Dr. Sara encourages a similar approach in his staff. He warns them about the “hero syndrome,” in which dying patients are made to feel they need to “hang on” and “fight” for the sake of their caregivers and families.

“The patient never asked to be the hero, but our attitude is telling him that he’s the hero,” he says in the film. “That puts him in an intolerable impasse because he figures that if he gives up, if he dies, he’s betraying his fans. He needs the exact opposite: to be set free. He needs the permission to die. That permission is given by two people: his doctor and his family.”

Of course, not all cancer patients have such a dim prognosis, and Dr. Sara is the first to forge ahead if he feels it’s appropriate. “If, if there is no option for them, I’m going to be aggressive to protect them. But when there is a curable disease, I will go broke to try to treat my patient. I’m willing to give them toxic drugs and hold their hand, get them through the storm if I believe it’s going to cure what they have, and I will coach them to accept being sick.”

He also believes in physical contact with the patient. “If we have some intimacy with the patient, we can at least palpate the kind of person they are,” he said. But his wife Nada pointed out that physical examinations can sometimes make patients nervous. “She told me, if you have a tie, they might have fun looking at it.” Thus began Dr. Sara’s collection of about 30 fun ties decorated with unicorns or jellyfish tailored to various patients’ preferences.

In the film, his patient teases him about this quirk, but Dr. Sara insists it is a small gesture that carries meaning. “One patient told me a story about lovebugs. She would see them in her kitchen when she was feeling well – so lovebugs became a sign of hope for her. I was telling the story to my wife ... so she got me a tie with lovebugs on it, and my patient was so happy when she saw me wearing that.”

In the film – and in real life – Dr. Sara often played guitar at breakfast music sessions with his staff in which he encouraged them to express their feelings about patients’ struggles. “If you cry, don’t be ashamed. Your patient will feel you’re with him,” he said in the film. In the final scenes, wearing a cloud-covered tie, he says goodbye to his patient with tears in his eyes. “They [the tears] are sincere,” he recalled. “Because I really felt I was looking at a dying patient. I really did.”

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

When New York oncologist Gabriel Sara, MD, approached the French actress and film director Emmanuelle Bercot after a screening of one of her films in Manhattan, he was thinking big.

He never dreamed she would think bigger.  

“I thought maybe she will do a movie about some of my beliefs,” he said.

“Ma’am, would you like to go in the trenches of cancer?” he asked her, inviting her to tour the oncology department at Mount Sinai West.

Whether it was the Lebanese-born doctor’s Parisian French, his gentle, double-handed handshake, or the perpetual twinkle in his eye, something convinced Ms. Bercot to go. After the visit, she decided to base an entire film on the doctor’s philosophy about death, and she even cast him as one of the leads.

With no formal training in acting, “it’s incredible and prodigious what he did,” Ms. Bercot said in an interview at the 2021 Cannes Film Festival, where the film, “Peaceful” (“De Son Vivant”) premiered.

“This is a guy we took from his cancer ward to a film set, and he was able to be as real and authentic as he is in his doctor’s office,” she said.

Dr. Sara said that authenticity came easily, given that “a lot of my dialogue – maybe most – came from things I shared with Emmanuelle,” he said in an interview with this news organization. “She took the information from me, and she created the whole story. She studied my character and came up with really all the messages that I was hoping to share.”

He said that acting alongside professionals was not intimidating once he realized he was simply playing himself. “At some point ... it clicked in my head. Let me stop acting – I should just be me,” he recalled.

“Peaceful,” performed in French with English subtitles, was nominated for Best Film at the 2022 Lumières Awards.

It tells the story of a 39-year-old man (played by French actor Benoît Magimel) diagnosed with stage 4 pancreatic cancer and the journey, along with his mother (played by renowned actress Catherine Deneuve), through diagnosis, denial, and eventual acceptance of his death.

It is also the story of an oncologist, played by Dr. Sara as himself, who takes his patient by the hand, and refuses to sugarcoat the truth, because he believes that it is only by facing the facts that patients can continue to live – and then die – in peace.

“You’ll never hear me say I’ll cure your cancer. I’d be a liar if I did,” he tells his patient in the film.

“Patients put their life in your hands, so if you don’t tell them the truth you are betraying them,” he explained in the interview. “I have refused to see patients whose family did not allow them to come to the consultation to hear the truth. ... Nobody hears the truth and feels great about it the next day, but the truth helps them focus on what they need to deal with. And once they focus, they’re in control ... a big part of what is terrible for patients is that loss of control.”

The approach may sound harsh, but it is conveyed tenderly in the film. “[Your mother] thinks that half-truths will hurt you half as much,” he tells his patient gently, but “the scariest thing is realizing someone is lying to you. ... We have a tough journey ahead, there’s no room for lies. ... For me, truth is nonnegotiable.”  

Dr. Sara is brimming with stories of real-life patients whose lives were enriched and empowered by the clarity they gained in knowing the full truth.

However, not all oncologists agree with his style.

After screenings of the film in other parts of the world, and even in the United States, he has encountered some physicians who strongly disagree with his uncompromising honesty. “You always have somebody who says you know, in America, you will receive the truth but not in our culture – people are not used to it. I hear this all the time,” he said.

“And a long time ago, I decided I’m not going to accept that conversation. Truth works with all patients across all cultures,” Dr. Sara insisted.

“However, as caregivers, we have to be sensitive and present to the kind of culture we are dealing with. The content has to be always 100% honest but we adapt our language to the cultural and emotional state of the patient in order to successfully transmit the message,” he added.

Helping patients digest the news of their diagnosis and prognosis has been Dr. Sara’s recipe for his own survival at work. Now 68 and recently retired as medical director of the chemotherapy infusion suite and executive director of the patient services initiative at Mount Sinai West, he says he emerged from 40 years of practice without burning out by learning to step in time with each patient.

“My recipe for it is tango,” he said. Regular tango performances on his cancer ward were among his many real-life techniques that Ms. Bercot incorporated into the film. “I feel that we have to dance closely with our patients’ emotion,” he explained. “We have to feel our patients’ emotion and work with that. If you don’t move in harmony with your partner, you trip together and both of you will fall,” he told an audience after a screening of his film in New York City.

“I completely try to isolate my mind from anything else in order to be with the patient – this is what presence is about for me – to be right there for them, close to them. To spend that whole moment with them. That’s what will make the consultation really helpful, and will make me feel that I can move to the next page without feeling exhausted from the first one.”

A key scene in the film comes after the patient’s mother is stunned to discover a cheerful tango performance on her son’s ward, and confronts the doctor angrily.

“It’s like I’m abandoning him,” she says tearfully, when the doctor urges her to accept that her son’s chemotherapy is no longer working and let him live what life he has left.

“Give him permission to go,” he urges her. “It would be your greatest gift of love.”

Dr. Sara encourages a similar approach in his staff. He warns them about the “hero syndrome,” in which dying patients are made to feel they need to “hang on” and “fight” for the sake of their caregivers and families.

“The patient never asked to be the hero, but our attitude is telling him that he’s the hero,” he says in the film. “That puts him in an intolerable impasse because he figures that if he gives up, if he dies, he’s betraying his fans. He needs the exact opposite: to be set free. He needs the permission to die. That permission is given by two people: his doctor and his family.”

Of course, not all cancer patients have such a dim prognosis, and Dr. Sara is the first to forge ahead if he feels it’s appropriate. “If, if there is no option for them, I’m going to be aggressive to protect them. But when there is a curable disease, I will go broke to try to treat my patient. I’m willing to give them toxic drugs and hold their hand, get them through the storm if I believe it’s going to cure what they have, and I will coach them to accept being sick.”

He also believes in physical contact with the patient. “If we have some intimacy with the patient, we can at least palpate the kind of person they are,” he said. But his wife Nada pointed out that physical examinations can sometimes make patients nervous. “She told me, if you have a tie, they might have fun looking at it.” Thus began Dr. Sara’s collection of about 30 fun ties decorated with unicorns or jellyfish tailored to various patients’ preferences.

In the film, his patient teases him about this quirk, but Dr. Sara insists it is a small gesture that carries meaning. “One patient told me a story about lovebugs. She would see them in her kitchen when she was feeling well – so lovebugs became a sign of hope for her. I was telling the story to my wife ... so she got me a tie with lovebugs on it, and my patient was so happy when she saw me wearing that.”

In the film – and in real life – Dr. Sara often played guitar at breakfast music sessions with his staff in which he encouraged them to express their feelings about patients’ struggles. “If you cry, don’t be ashamed. Your patient will feel you’re with him,” he said in the film. In the final scenes, wearing a cloud-covered tie, he says goodbye to his patient with tears in his eyes. “They [the tears] are sincere,” he recalled. “Because I really felt I was looking at a dying patient. I really did.”

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

The American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI) have jointly issued new guidance outlining competency-based advanced training requirements for interventional cardiology trainees.

It’s the first document of its kind to define the training requirements for the full breadth of interventional cardiology for adults, including coronary interventions, peripheral vascular interventions (PVIs), and structural heart interventions (SHIs), the organizations say.

enot-poloskun/Getty Images

Minimum of 250 procedures

To gain the necessary experience in interventional cardiology, cardiovascular fellows are advised to complete the following:

• A 3-year general cardiovascular disease fellowship (successful completion consists of Level I competency in all aspects of cardiovascular medicine and Level II competency in diagnostic cardiac catheterization to pursue interventional cardiology training);
• A 1-year accredited interventional cardiology fellowship, the focus of which is coronary intervention with the opportunity to gain procedural experience in various aspects of PVI or SHI (Level III competency);
• An option for additional post-fellowship training based on the trainee’s career goals.

The goal of Level III training is to provide the interventional cardiology trainees with a “well-rounded, competency-based education,” including didactic instruction, clinical experience in the diagnosis and care of patients, and hands-on procedural experience, the writing group says.

Competency requirements are defined using the Accreditation Council for Graduate Medical Education’s six “essential” competency domains: medical knowledge; patient care and procedural skills; practice-based learning and improvement; systems-based practice; interpersonal and communication skills; and professionalism.

To support attaining these competencies, the writing committee recommends a minimum of 250 interventional cardiology procedures. Of these, 200 should be coronary procedures, with the remaining 50 specialized in coronary, PVI, or SHI, which allows the fellows to customize training on the basis of their career goals.

Adjunctive procedures related to physiologic assessment and intracoronary imaging are also required (25 of each). “These minimum numbers are meant to provide trainees with exposure to a variety and spectrum of complexity of clinical case material and give supervising faculty sufficient opportunity to evaluate trainees’ competency,” the writing group says.

In addition to their procedural skills, evaluation of interventional cardiology trainee proficiency should include regular assessment of a trainee’s ability to clinically diagnose and manage patients across the broad spectrum of diseases.

Assessment of trainees should involve multiple components, including direct observation by instructors, case logs, chart reviews (including adherence to guideline recommendations, appropriate use criteria, and patient outcomes), simulation training, and assessment of leadership skills.

Trainees must also acquire experience working as part of a multidisciplinary team to provide a holistic approach to patient care. The document also highlights the importance of leadership skills, mentorship and lifelong learning beyond initial training.

The 2023 ACC/AHA/SCAI Advanced Training Statement on Interventional Cardiology (Coronary, Peripheral Vascular, and Structural Heart Interventions) was published online in the Journal of the American College of Cardiology.

The statement was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American Society of Echocardiography, the Heart Failure Society of America, the Heart Rhythm Society, the Society of Cardiovascular Anesthesiologists, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

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

The American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI) have jointly issued new guidance outlining competency-based advanced training requirements for interventional cardiology trainees.

It’s the first document of its kind to define the training requirements for the full breadth of interventional cardiology for adults, including coronary interventions, peripheral vascular interventions (PVIs), and structural heart interventions (SHIs), the organizations say.

enot-poloskun/Getty Images

Minimum of 250 procedures

To gain the necessary experience in interventional cardiology, cardiovascular fellows are advised to complete the following:

• A 3-year general cardiovascular disease fellowship (successful completion consists of Level I competency in all aspects of cardiovascular medicine and Level II competency in diagnostic cardiac catheterization to pursue interventional cardiology training);
• A 1-year accredited interventional cardiology fellowship, the focus of which is coronary intervention with the opportunity to gain procedural experience in various aspects of PVI or SHI (Level III competency);
• An option for additional post-fellowship training based on the trainee’s career goals.

The goal of Level III training is to provide the interventional cardiology trainees with a “well-rounded, competency-based education,” including didactic instruction, clinical experience in the diagnosis and care of patients, and hands-on procedural experience, the writing group says.

Competency requirements are defined using the Accreditation Council for Graduate Medical Education’s six “essential” competency domains: medical knowledge; patient care and procedural skills; practice-based learning and improvement; systems-based practice; interpersonal and communication skills; and professionalism.

To support attaining these competencies, the writing committee recommends a minimum of 250 interventional cardiology procedures. Of these, 200 should be coronary procedures, with the remaining 50 specialized in coronary, PVI, or SHI, which allows the fellows to customize training on the basis of their career goals.

Adjunctive procedures related to physiologic assessment and intracoronary imaging are also required (25 of each). “These minimum numbers are meant to provide trainees with exposure to a variety and spectrum of complexity of clinical case material and give supervising faculty sufficient opportunity to evaluate trainees’ competency,” the writing group says.

In addition to their procedural skills, evaluation of interventional cardiology trainee proficiency should include regular assessment of a trainee’s ability to clinically diagnose and manage patients across the broad spectrum of diseases.

Assessment of trainees should involve multiple components, including direct observation by instructors, case logs, chart reviews (including adherence to guideline recommendations, appropriate use criteria, and patient outcomes), simulation training, and assessment of leadership skills.

Trainees must also acquire experience working as part of a multidisciplinary team to provide a holistic approach to patient care. The document also highlights the importance of leadership skills, mentorship and lifelong learning beyond initial training.

The 2023 ACC/AHA/SCAI Advanced Training Statement on Interventional Cardiology (Coronary, Peripheral Vascular, and Structural Heart Interventions) was published online in the Journal of the American College of Cardiology.

The statement was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American Society of Echocardiography, the Heart Failure Society of America, the Heart Rhythm Society, the Society of Cardiovascular Anesthesiologists, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

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

The American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI) have jointly issued new guidance outlining competency-based advanced training requirements for interventional cardiology trainees.

It’s the first document of its kind to define the training requirements for the full breadth of interventional cardiology for adults, including coronary interventions, peripheral vascular interventions (PVIs), and structural heart interventions (SHIs), the organizations say.

enot-poloskun/Getty Images

Minimum of 250 procedures

To gain the necessary experience in interventional cardiology, cardiovascular fellows are advised to complete the following:

• A 3-year general cardiovascular disease fellowship (successful completion consists of Level I competency in all aspects of cardiovascular medicine and Level II competency in diagnostic cardiac catheterization to pursue interventional cardiology training);
• A 1-year accredited interventional cardiology fellowship, the focus of which is coronary intervention with the opportunity to gain procedural experience in various aspects of PVI or SHI (Level III competency);
• An option for additional post-fellowship training based on the trainee’s career goals.

The goal of Level III training is to provide the interventional cardiology trainees with a “well-rounded, competency-based education,” including didactic instruction, clinical experience in the diagnosis and care of patients, and hands-on procedural experience, the writing group says.

Competency requirements are defined using the Accreditation Council for Graduate Medical Education’s six “essential” competency domains: medical knowledge; patient care and procedural skills; practice-based learning and improvement; systems-based practice; interpersonal and communication skills; and professionalism.

To support attaining these competencies, the writing committee recommends a minimum of 250 interventional cardiology procedures. Of these, 200 should be coronary procedures, with the remaining 50 specialized in coronary, PVI, or SHI, which allows the fellows to customize training on the basis of their career goals.

Adjunctive procedures related to physiologic assessment and intracoronary imaging are also required (25 of each). “These minimum numbers are meant to provide trainees with exposure to a variety and spectrum of complexity of clinical case material and give supervising faculty sufficient opportunity to evaluate trainees’ competency,” the writing group says.

In addition to their procedural skills, evaluation of interventional cardiology trainee proficiency should include regular assessment of a trainee’s ability to clinically diagnose and manage patients across the broad spectrum of diseases.

Assessment of trainees should involve multiple components, including direct observation by instructors, case logs, chart reviews (including adherence to guideline recommendations, appropriate use criteria, and patient outcomes), simulation training, and assessment of leadership skills.

Trainees must also acquire experience working as part of a multidisciplinary team to provide a holistic approach to patient care. The document also highlights the importance of leadership skills, mentorship and lifelong learning beyond initial training.

The 2023 ACC/AHA/SCAI Advanced Training Statement on Interventional Cardiology (Coronary, Peripheral Vascular, and Structural Heart Interventions) was published online in the Journal of the American College of Cardiology.

The statement was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, the American Society of Echocardiography, the Heart Failure Society of America, the Heart Rhythm Society, the Society of Cardiovascular Anesthesiologists, the Society of Cardiovascular Computed Tomography, the Society for Cardiovascular Magnetic Resonance, the Society of Thoracic Surgeons, and the Society for Vascular Medicine.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

In the first study to examine how intermittent fasting combined with exercise impacts nonalcoholic fatty liver disease (NAFLD), the combined strategy was more effective than aerobic exercise alone or no intervention (control).

However, the combined approach did not give significantly added benefit, compared with fasting alone, the researchers report.

Eighty patients with NAFLD were randomized to one of four lifestyle strategies (alternate-day fasting, aerobic exercise, both, or neither) for 3 months.

The primary outcome was change in intrahepatic triglyceride (IHTG) content from baseline to study end, measured by magnetic resonance imaging proton density fat fraction.

The results suggest that “combining intermittent fasting with exercise is effective for reducing hepatic steatosis [fatty liver] in patients with NAFLD but may offer no additional benefit versus fasting alone,” Mark Ezpeleta, PhD, formerly at the University of Illinois, Chicago, and now at the University of Colorado Anschutz Medical Campus, and colleagues conclude.

“Our findings also indicate that the combination intervention was effective for reducing body weight, fat mass, waist circumference, [the liver enzyme alanine transaminase (ALT)], fasting insulin, [and] insulin resistance and increasing insulin sensitivity, among patients with obesity and NAFLD versus controls,” the group reports.  

“When we compared the results of our study groups, we saw clearly that the most improved patients were in the group that followed the alternate-day fasting diet and exercised 5 days a week,” senior author Krista A. Varady, PhD, professor of nutrition, University of Illinois, said in a press release from the university.

“The people who only dieted or only exercised did not see the same improvements,” she added, “which reinforces the importance of these two relatively inexpensive lifestyle modifications on overall health and on combating chronic diseases like fatty liver disease.”

Moreover, “alternate-day fasting and exercise interventions can be difficult for people to stick to, and in prior studies we have seen significant dropout,” she noted. “It was very interesting to see that in this trial we had very high adherence to the interventions.”

The study was recently published in Cell Metabolism.  

An estimated 65% of people with obesity have NAFLD, or fat in the liver that is not the result of excessive alcohol consumption, which is strongly related to the development of insulin resistance and type 2 diabetes, the group writes.

Thiazolidinediones such as pioglitazone reduce hepatic steatosis, but there is mounting concern about the weight-gaining effect of these compounds.

Recent attention has focused on lifestyle interventions to resolve hepatic steatosis, and previous trials showed that alternate-day fasting was effective for certain outcomes in NAFLD, but those studies did not measure changes in IHTG content or include an exercise intervention.

The researchers enrolled 80 adults with obesity and NAFLD and randomized them to one of four groups for 3 months:

• Alternate day fasting group: Participants were instructed to consume 600 kcal at dinner between 5 PM and 8 PM on a fasting day alternating with food as desired on a feasting day.
• Exercise group: A 60-minute moderate-intensity aerobic exercise session 5 times a week.
• Fasting plus exercise group.
• Control group (no intervention).

Participants were age 23-65 (mean age, 44) and 81% were women.

Half were Hispanic, and the rest were Black (30%), White (11%), or Asian (9%).

They had a mean weight of 99 kg (218 lb) and a mean body mass index of 36 kg/m².

Dropout rates were minimal in the combination group (0%) and fasting groups (5%) and moderately high in the exercise group (25%).

IHTG content was reduced by a significantly greater amount in the combination group (–5.48%) than in the exercise alone group (–1.30%; P = .02) or in the control group (–0.17%; P < .01) and by a greater amount than in the fasting alone group, although this was not significant (–2.25%; P = .05).

Lean mass, aspartate transaminase (AST), A1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups.

Researchers acknowledge that although the combination intervention resulted in improved NAFLD parameters, IHTG and ALT did not reach the normal range.  

Participants likely had early stage NAFLD (their baseline IHTG was in the 16% to 18% range, where 5% to 33% is mild steatosis) and they were likely highly motivated (indicated by the low dropout rate), so the findings may not be generalizable.

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Dr. Varady has reported receiving author fees from the Hachette Book Group for the book entitled “The Every Other Day Diet.” The other authors have reported no relevant financial relationships.

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

In a proof-of-concept feasibility study among adults with difficult-to-treat asthma and body mass index ≥ 30kg/m², an evidence-based, dietitian-led program resulted in clinically important improvements in asthma control and quality of life over 16 weeks compared to usual care.

The Counterweight-Plus weight management program (CWP) used in the study includes 12 weeks of total diet replacement (TDR), stepwise food reintroduction in weeks 13-18, and weight loss maintenance up to 1 year, according to a report by Varun Sharma, MBChB, and fellow researchers at University of Glasgow.

Difficult-to-treat asthma, found among about 17% of asthma-affected patients, may be attributed to factors such as poor inhaler technique, treatment nonadherence, and comorbidities such as obesity. Obesity is frequently associated with difficult-to-treat, uncontrolled asthma and increased morbidity and mortality. Among multifactorial effects of obesity on asthma are direct ones on thoracic wall mechanics, increased airway closure, airway hyper-responsiveness and airway inflammation. Prior research showing that weight loss may improve asthma outcomes has been conducted among heterogeneous asthma populations, with no clear consensus regarding optimal methods of weight management, according to the authors.

They tested whether use of the CWP compared to usual care (1:1) would improve asthma control and quality of life in this population of patients with obesity. The TDR phase comprised a low-energy liquid diet consisting of 825-853 kcal/day (approximately 59% carbohydrate, 13% fat, 26% protein, 2% fiber), with meals supplied dried in sachets by the dietitian team and reconstituted with water by the participants. A review by the dietitian team at 1 week was followed by reviews every other week.

The primary outcome was difference in change in Asthma Control Questionnaire (ACQ6) from baseline (visit 1) to 16 weeks (visit 2), between CWP and usual care.

The single-center trial included 33 evaluable adult patients (75 years or younger; mean age 53 years; 63% women) with asthma (as per Global Initiative for Asthma guidelines) that was difficult to treat (as per Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines). The study population consisted of patients with frequent exacerbations with uncontrolled disease as reflected by the median interquartile range (IQR) for oral corticosteroid courses in the previous 12 months of 3 (2 to 5) and mean ACQ6 of 2.8 (2.4 to 3.1). Mean overall Asthma Quality of Life Questionnaire (AQLQ) was 3.8 (3.4 to 4.2). Median weight was 101.7 (91.4 to 118.7) kg, with a median BMI of 37.5 (35.0 to 42.3) kg/m². Recruitment was discontinued before the target of 40 patients because the CWP dropout rate (n = 2) was lower than expected.

The researchers reported that the mean change in ACQ6 over 16 weeks was –0.45 for CWP and 0.23 for usual care with a mean difference of –0.69 (P = .048) between groups. The secondary outcome of mean change in overall AQLQ was 0.81 for CWP and 0.08 for usual care with a mean difference of 0.76 (P = .013) between groups.

No unexpected serious adverse events or intervention-related adverse events were observed during the trial.

“In this pragmatic open label, randomized, controlled trial we showed that delivery of a supported low-calorie total diet replacement program (Counterweight-Plus) to patients with difficult-to treat asthma and obesity, was safe and led to significant improvements in asthma control and quality of life compared to usual care over 16 weeks,” the authors wrote.

“Findings from the study are a welcome addition to this field of study,” Diego J. Maselli, MD, associate professor of medicine and interim chief, division of pulmonary diseases and critical care, UT Health at San Antonio, said in an interview. “Over the past years there has been an increase in the focus of comorbid conditions that may influence asthma control, particularly in severe disease.  Obesity is an important comorbid condition because, although by itself it may have an effect on asthma patients, it is also associated with other comorbidities such as gastroesophageal reflux disease, obstructive sleep apnea, anxiety, depression, and others that in turn can affect asthmatics. Also, obesity may influence pulmonary physiology and it’s considered a proinflammatory state by many, and this can favor uncontrolled disease.”  

While underscoring the clinically relevant weight loss and improvements in ACQ6 and AQLQ, Dr. Maselli said that the study did not follow the patients long enough to determine if weight loss was associated with a reduction in exacerbations and other long-term outcomes in asthma such as resource utilization and changes in maintenance medications, which may be explored in future studies.

“It remains to be seen if the weight loss of these types of programs can be sustained over longer periods of time, given the considerable caloric restriction in the initial stages of the weight reduction program. Interestingly, the majority of the patients in the study did not exhibit features of type 2 inflammation and had low-T2 endotype with low eosinophil count and low FeNO [fractional exhaled nitric oxide],” Dr. Maselli added. “Although obesity has been linked to this phenotype, the vast majority of [people with asthma], about 80%, have high T2 phenotype. Future studies are still need with larger and more representative samples and with longer follow-up times to determine the effects of weight loss on asthma outcomes, especially in severe asthma,” he concluded.

The trial was funded by an NHS Greater Glasgow and Clyde Endowment Fund grant. Several of the authors reported having received travel awards to attend conferences and funding from Cambridge Weight Plan and one author is an employee of and another a medical adviser for Counterweight Ltd., the developer of the program used. Other authors reported receiving funding from a variety of pharmaceutical companies. Dr. Maselli reported no relevant conflicts.

In a proof-of-concept feasibility study among adults with difficult-to-treat asthma and body mass index ≥ 30kg/m², an evidence-based, dietitian-led program resulted in clinically important improvements in asthma control and quality of life over 16 weeks compared to usual care.

The Counterweight-Plus weight management program (CWP) used in the study includes 12 weeks of total diet replacement (TDR), stepwise food reintroduction in weeks 13-18, and weight loss maintenance up to 1 year, according to a report by Varun Sharma, MBChB, and fellow researchers at University of Glasgow.

Difficult-to-treat asthma, found among about 17% of asthma-affected patients, may be attributed to factors such as poor inhaler technique, treatment nonadherence, and comorbidities such as obesity. Obesity is frequently associated with difficult-to-treat, uncontrolled asthma and increased morbidity and mortality. Among multifactorial effects of obesity on asthma are direct ones on thoracic wall mechanics, increased airway closure, airway hyper-responsiveness and airway inflammation. Prior research showing that weight loss may improve asthma outcomes has been conducted among heterogeneous asthma populations, with no clear consensus regarding optimal methods of weight management, according to the authors.

They tested whether use of the CWP compared to usual care (1:1) would improve asthma control and quality of life in this population of patients with obesity. The TDR phase comprised a low-energy liquid diet consisting of 825-853 kcal/day (approximately 59% carbohydrate, 13% fat, 26% protein, 2% fiber), with meals supplied dried in sachets by the dietitian team and reconstituted with water by the participants. A review by the dietitian team at 1 week was followed by reviews every other week.

The primary outcome was difference in change in Asthma Control Questionnaire (ACQ6) from baseline (visit 1) to 16 weeks (visit 2), between CWP and usual care.

The single-center trial included 33 evaluable adult patients (75 years or younger; mean age 53 years; 63% women) with asthma (as per Global Initiative for Asthma guidelines) that was difficult to treat (as per Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines). The study population consisted of patients with frequent exacerbations with uncontrolled disease as reflected by the median interquartile range (IQR) for oral corticosteroid courses in the previous 12 months of 3 (2 to 5) and mean ACQ6 of 2.8 (2.4 to 3.1). Mean overall Asthma Quality of Life Questionnaire (AQLQ) was 3.8 (3.4 to 4.2). Median weight was 101.7 (91.4 to 118.7) kg, with a median BMI of 37.5 (35.0 to 42.3) kg/m². Recruitment was discontinued before the target of 40 patients because the CWP dropout rate (n = 2) was lower than expected.

The researchers reported that the mean change in ACQ6 over 16 weeks was –0.45 for CWP and 0.23 for usual care with a mean difference of –0.69 (P = .048) between groups. The secondary outcome of mean change in overall AQLQ was 0.81 for CWP and 0.08 for usual care with a mean difference of 0.76 (P = .013) between groups.

No unexpected serious adverse events or intervention-related adverse events were observed during the trial.

“In this pragmatic open label, randomized, controlled trial we showed that delivery of a supported low-calorie total diet replacement program (Counterweight-Plus) to patients with difficult-to treat asthma and obesity, was safe and led to significant improvements in asthma control and quality of life compared to usual care over 16 weeks,” the authors wrote.

“Findings from the study are a welcome addition to this field of study,” Diego J. Maselli, MD, associate professor of medicine and interim chief, division of pulmonary diseases and critical care, UT Health at San Antonio, said in an interview. “Over the past years there has been an increase in the focus of comorbid conditions that may influence asthma control, particularly in severe disease.  Obesity is an important comorbid condition because, although by itself it may have an effect on asthma patients, it is also associated with other comorbidities such as gastroesophageal reflux disease, obstructive sleep apnea, anxiety, depression, and others that in turn can affect asthmatics. Also, obesity may influence pulmonary physiology and it’s considered a proinflammatory state by many, and this can favor uncontrolled disease.”  

While underscoring the clinically relevant weight loss and improvements in ACQ6 and AQLQ, Dr. Maselli said that the study did not follow the patients long enough to determine if weight loss was associated with a reduction in exacerbations and other long-term outcomes in asthma such as resource utilization and changes in maintenance medications, which may be explored in future studies.

“It remains to be seen if the weight loss of these types of programs can be sustained over longer periods of time, given the considerable caloric restriction in the initial stages of the weight reduction program. Interestingly, the majority of the patients in the study did not exhibit features of type 2 inflammation and had low-T2 endotype with low eosinophil count and low FeNO [fractional exhaled nitric oxide],” Dr. Maselli added. “Although obesity has been linked to this phenotype, the vast majority of [people with asthma], about 80%, have high T2 phenotype. Future studies are still need with larger and more representative samples and with longer follow-up times to determine the effects of weight loss on asthma outcomes, especially in severe asthma,” he concluded.

The trial was funded by an NHS Greater Glasgow and Clyde Endowment Fund grant. Several of the authors reported having received travel awards to attend conferences and funding from Cambridge Weight Plan and one author is an employee of and another a medical adviser for Counterweight Ltd., the developer of the program used. Other authors reported receiving funding from a variety of pharmaceutical companies. Dr. Maselli reported no relevant conflicts.

In a proof-of-concept feasibility study among adults with difficult-to-treat asthma and body mass index ≥ 30kg/m², an evidence-based, dietitian-led program resulted in clinically important improvements in asthma control and quality of life over 16 weeks compared to usual care.

The Counterweight-Plus weight management program (CWP) used in the study includes 12 weeks of total diet replacement (TDR), stepwise food reintroduction in weeks 13-18, and weight loss maintenance up to 1 year, according to a report by Varun Sharma, MBChB, and fellow researchers at University of Glasgow.

Difficult-to-treat asthma, found among about 17% of asthma-affected patients, may be attributed to factors such as poor inhaler technique, treatment nonadherence, and comorbidities such as obesity. Obesity is frequently associated with difficult-to-treat, uncontrolled asthma and increased morbidity and mortality. Among multifactorial effects of obesity on asthma are direct ones on thoracic wall mechanics, increased airway closure, airway hyper-responsiveness and airway inflammation. Prior research showing that weight loss may improve asthma outcomes has been conducted among heterogeneous asthma populations, with no clear consensus regarding optimal methods of weight management, according to the authors.

They tested whether use of the CWP compared to usual care (1:1) would improve asthma control and quality of life in this population of patients with obesity. The TDR phase comprised a low-energy liquid diet consisting of 825-853 kcal/day (approximately 59% carbohydrate, 13% fat, 26% protein, 2% fiber), with meals supplied dried in sachets by the dietitian team and reconstituted with water by the participants. A review by the dietitian team at 1 week was followed by reviews every other week.

The primary outcome was difference in change in Asthma Control Questionnaire (ACQ6) from baseline (visit 1) to 16 weeks (visit 2), between CWP and usual care.

The single-center trial included 33 evaluable adult patients (75 years or younger; mean age 53 years; 63% women) with asthma (as per Global Initiative for Asthma guidelines) that was difficult to treat (as per Scottish Intercollegiate Guidelines Network/British Thoracic Society guidelines). The study population consisted of patients with frequent exacerbations with uncontrolled disease as reflected by the median interquartile range (IQR) for oral corticosteroid courses in the previous 12 months of 3 (2 to 5) and mean ACQ6 of 2.8 (2.4 to 3.1). Mean overall Asthma Quality of Life Questionnaire (AQLQ) was 3.8 (3.4 to 4.2). Median weight was 101.7 (91.4 to 118.7) kg, with a median BMI of 37.5 (35.0 to 42.3) kg/m². Recruitment was discontinued before the target of 40 patients because the CWP dropout rate (n = 2) was lower than expected.

The researchers reported that the mean change in ACQ6 over 16 weeks was –0.45 for CWP and 0.23 for usual care with a mean difference of –0.69 (P = .048) between groups. The secondary outcome of mean change in overall AQLQ was 0.81 for CWP and 0.08 for usual care with a mean difference of 0.76 (P = .013) between groups.

No unexpected serious adverse events or intervention-related adverse events were observed during the trial.

“In this pragmatic open label, randomized, controlled trial we showed that delivery of a supported low-calorie total diet replacement program (Counterweight-Plus) to patients with difficult-to treat asthma and obesity, was safe and led to significant improvements in asthma control and quality of life compared to usual care over 16 weeks,” the authors wrote.

“Findings from the study are a welcome addition to this field of study,” Diego J. Maselli, MD, associate professor of medicine and interim chief, division of pulmonary diseases and critical care, UT Health at San Antonio, said in an interview. “Over the past years there has been an increase in the focus of comorbid conditions that may influence asthma control, particularly in severe disease.  Obesity is an important comorbid condition because, although by itself it may have an effect on asthma patients, it is also associated with other comorbidities such as gastroesophageal reflux disease, obstructive sleep apnea, anxiety, depression, and others that in turn can affect asthmatics. Also, obesity may influence pulmonary physiology and it’s considered a proinflammatory state by many, and this can favor uncontrolled disease.”  

While underscoring the clinically relevant weight loss and improvements in ACQ6 and AQLQ, Dr. Maselli said that the study did not follow the patients long enough to determine if weight loss was associated with a reduction in exacerbations and other long-term outcomes in asthma such as resource utilization and changes in maintenance medications, which may be explored in future studies.

“It remains to be seen if the weight loss of these types of programs can be sustained over longer periods of time, given the considerable caloric restriction in the initial stages of the weight reduction program. Interestingly, the majority of the patients in the study did not exhibit features of type 2 inflammation and had low-T2 endotype with low eosinophil count and low FeNO [fractional exhaled nitric oxide],” Dr. Maselli added. “Although obesity has been linked to this phenotype, the vast majority of [people with asthma], about 80%, have high T2 phenotype. Future studies are still need with larger and more representative samples and with longer follow-up times to determine the effects of weight loss on asthma outcomes, especially in severe asthma,” he concluded.

The trial was funded by an NHS Greater Glasgow and Clyde Endowment Fund grant. Several of the authors reported having received travel awards to attend conferences and funding from Cambridge Weight Plan and one author is an employee of and another a medical adviser for Counterweight Ltd., the developer of the program used. Other authors reported receiving funding from a variety of pharmaceutical companies. Dr. Maselli reported no relevant conflicts.

Adults with the inflammatory autoimmune myopathy dermatomyositis are at increased for concurrent cancers, but new research suggests that certain autoantibodies in patients with a specific dermatomyositis subtype may actually protect against cancer.

A study of cohorts of patients with dermatomyositis, other rheumatic diseases, and those without disease showed that among patients with dermatomyositis positive for antitranscriptional intermediary factor 1 (anti–TIF1-gamma) autoantibodies – a disease subtype associated with increased cancer risk – the presence of autoantibodies directed against cell division cycle and apoptosis regulator 1 (CCAR1) was associated with reduced cancer risk “to a level comparable to that seen in the general population,” Christopher A. Mecoli, MD, MHS, of Johns Hopkins University, Baltimore, and colleagues reported.

“Our prior data suggest that there are autoantigens that, when targeted simultaneously with CCAR1, provide additional cancer protection. Although these autoantigens are less frequently targeted, it is likely that additional, more prevalent ‘autoantigen hubs’ remain undiscovered,” they wrote in Arthritis & Rheumatology.

Identification of other autoantibodies both in the anti–TIF1-gamma–positive and other dermatomyositis subgroups may help with cancer risk stratification in patients with the disease and may ultimately improve cancer screening for adults with dermatomyositis, the investigators said.
 

Toward precision medicine

“I think this is a step toward precision medicine in patients with rheumatic disease, specifically myositis,” Dr. Mecoli said in an interview.

The study supports earlier work showing that dermatomyositis and related myopathies are heterogeneous, he said, noting that, “if you put 10 myositis patients in the same room, you wouldn’t get that they all have the same disease because they can look so different from one another.”

The association of dermatomyositis with concurrent cancers has been known for decades, but in recent years his team and other investigators have noted that the association holds true for only some patients with dermatomyositis, most notably those patients positive for anti–TIF1-gamma autoantibodies.

“And then, of course, once you really start studying just one gamma-positive dermatomyositis patient, you realize that even among that group it is heterogeneous in terms of their cancer risk, and that was the main focus of this study: to reconcile this clinical observation that I had a lot of patients with TIF1-gamma dermatomyositis who never get diagnosed with cancer,” Dr. Mecoli said.

Study details

Dr. Dr. Mecoli and colleagues previously reported that immune responses to CCAR1 and other autoantigens seen in patients with dermatomyositis were associated with lower probability of cancer occurrence.

In the current study, they focused on the disease specificity, clinical phenotype, and cancer risk for patients with dermatomyositis and anti-CCAR1 autoantibodies.

They looked at all patients aged 18 or older with a probable or definite finding of dermatomyositis, according to 2017 American College of Rheumatology/European Alliance of Associations for Rheumatology Idiopathic Inflammatory Myopathy criteria, who were seen at Stanford (Calif.) University Medical Center from August 2004 to April 2020 (101 patients), or the Johns Hopkins Myositis Center (141 patients) from January 2007 to December 2020.

Controls included 44 patients evaluated at the Johns Hopkins Myositis Center with immune-mediated necrotizing myopathy, 186 patients with anti–TIF1-gamma–negative dermatomyositis (defined as an enzyme-linked immunosorbent assay readout of less than seven units) evaluated at either Stanford or Johns Hopkins, 44 patients with inclusion body myositis evaluated at Johns Hopkins, and 46 patients with systemic lupus erythematosus from the Hopkins Lupus Cohort. The investigators also assayed serum from 32 healthy individuals.

They found that patients with anti–TIF1-gamma–positive dermatomyositis were significantly more likely than those with anti–TIF1-gamma–negative dermatomyositis to have anti-CCAR1 autoantibodies (32% vs. 8%; P < .001). Additionally, they noted that the anti-CCAR1 autoantibodies were not seen in serum from healthy controls and were found at only very low frequencies among patients with other rheumatic diseases.

When they looked at the incidence of cancer from the time of dermatomyositis onset (defined as the first patient-reported symptoms of rash, weakness, myalgia, or dyspnea) they found that the standardized incidence ratio in anti–TIF1-gamma–positive patients in both the Stanford and Hopkins cohorts was higher than expected, with SIRs of 3.49 and 4.54, respectively (P < .001 for each comparison).

However, among those patients who were both anti–TIF1-gamma positive and anti-CCAR1 positive, the SIRs were 1.78 in the Stanford cohort and 1.61 in the Hopkins cohort, and neither SIR was significantly higher than that of the general population.
 

Risk prediction

Their findings suggest that autoantibody profiles might be used for cancer risk stratification in patients with anti–TIF1-gamma–positive dermatomyositis, Dr. Mecoli said.

“Are we overscreening? What is the cost in terms of patient anxiety, in terms of radiation, and in terms of false positive results?” he asked. “If I had a patient in front of me with anti–TIF1-gamma dermatomyositis, I would probably manage them differently if I knew that they were CCAR1 positive, because the presence of that additional autoantibody attenuates their cancer risk relative to the general population.”

In an editorial accompanying the study, Manabu Fujimoto, MD, of the department of dermatology at Osaka (Japan) University, commented that it “is of clinical importance in that combination of autoantibodies can predict cancer risk with more accuracy. At the same time, this study will give an insight into the pathomechanisms of how antitumor activity may shape autoimmunity in dermatomyositis.”

It will be “intriguing” to discover whether anti-CCAR1 autoantibodies act only against tumors or might also have an impact on dermatomyositis itself, Dr. Fujimoto said.

The research was supported by grants from the National Institutes of Health; Huayi and Siuling Zhang Discovery Fund; Peter Buck, MD; and the Donald B. and Dorothy L. Stabler Foundation. The authors and Dr. Fujimoto reported no relevant financial relationships.

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

Adults with the inflammatory autoimmune myopathy dermatomyositis are at increased for concurrent cancers, but new research suggests that certain autoantibodies in patients with a specific dermatomyositis subtype may actually protect against cancer.

A study of cohorts of patients with dermatomyositis, other rheumatic diseases, and those without disease showed that among patients with dermatomyositis positive for antitranscriptional intermediary factor 1 (anti–TIF1-gamma) autoantibodies – a disease subtype associated with increased cancer risk – the presence of autoantibodies directed against cell division cycle and apoptosis regulator 1 (CCAR1) was associated with reduced cancer risk “to a level comparable to that seen in the general population,” Christopher A. Mecoli, MD, MHS, of Johns Hopkins University, Baltimore, and colleagues reported.

“Our prior data suggest that there are autoantigens that, when targeted simultaneously with CCAR1, provide additional cancer protection. Although these autoantigens are less frequently targeted, it is likely that additional, more prevalent ‘autoantigen hubs’ remain undiscovered,” they wrote in Arthritis & Rheumatology.

Identification of other autoantibodies both in the anti–TIF1-gamma–positive and other dermatomyositis subgroups may help with cancer risk stratification in patients with the disease and may ultimately improve cancer screening for adults with dermatomyositis, the investigators said.
 

Toward precision medicine

“I think this is a step toward precision medicine in patients with rheumatic disease, specifically myositis,” Dr. Mecoli said in an interview.

The study supports earlier work showing that dermatomyositis and related myopathies are heterogeneous, he said, noting that, “if you put 10 myositis patients in the same room, you wouldn’t get that they all have the same disease because they can look so different from one another.”

The association of dermatomyositis with concurrent cancers has been known for decades, but in recent years his team and other investigators have noted that the association holds true for only some patients with dermatomyositis, most notably those patients positive for anti–TIF1-gamma autoantibodies.

“And then, of course, once you really start studying just one gamma-positive dermatomyositis patient, you realize that even among that group it is heterogeneous in terms of their cancer risk, and that was the main focus of this study: to reconcile this clinical observation that I had a lot of patients with TIF1-gamma dermatomyositis who never get diagnosed with cancer,” Dr. Mecoli said.

Study details

Dr. Dr. Mecoli and colleagues previously reported that immune responses to CCAR1 and other autoantigens seen in patients with dermatomyositis were associated with lower probability of cancer occurrence.

In the current study, they focused on the disease specificity, clinical phenotype, and cancer risk for patients with dermatomyositis and anti-CCAR1 autoantibodies.

They looked at all patients aged 18 or older with a probable or definite finding of dermatomyositis, according to 2017 American College of Rheumatology/European Alliance of Associations for Rheumatology Idiopathic Inflammatory Myopathy criteria, who were seen at Stanford (Calif.) University Medical Center from August 2004 to April 2020 (101 patients), or the Johns Hopkins Myositis Center (141 patients) from January 2007 to December 2020.

Controls included 44 patients evaluated at the Johns Hopkins Myositis Center with immune-mediated necrotizing myopathy, 186 patients with anti–TIF1-gamma–negative dermatomyositis (defined as an enzyme-linked immunosorbent assay readout of less than seven units) evaluated at either Stanford or Johns Hopkins, 44 patients with inclusion body myositis evaluated at Johns Hopkins, and 46 patients with systemic lupus erythematosus from the Hopkins Lupus Cohort. The investigators also assayed serum from 32 healthy individuals.

They found that patients with anti–TIF1-gamma–positive dermatomyositis were significantly more likely than those with anti–TIF1-gamma–negative dermatomyositis to have anti-CCAR1 autoantibodies (32% vs. 8%; P < .001). Additionally, they noted that the anti-CCAR1 autoantibodies were not seen in serum from healthy controls and were found at only very low frequencies among patients with other rheumatic diseases.

When they looked at the incidence of cancer from the time of dermatomyositis onset (defined as the first patient-reported symptoms of rash, weakness, myalgia, or dyspnea) they found that the standardized incidence ratio in anti–TIF1-gamma–positive patients in both the Stanford and Hopkins cohorts was higher than expected, with SIRs of 3.49 and 4.54, respectively (P < .001 for each comparison).

However, among those patients who were both anti–TIF1-gamma positive and anti-CCAR1 positive, the SIRs were 1.78 in the Stanford cohort and 1.61 in the Hopkins cohort, and neither SIR was significantly higher than that of the general population.
 

Risk prediction

Their findings suggest that autoantibody profiles might be used for cancer risk stratification in patients with anti–TIF1-gamma–positive dermatomyositis, Dr. Mecoli said.

“Are we overscreening? What is the cost in terms of patient anxiety, in terms of radiation, and in terms of false positive results?” he asked. “If I had a patient in front of me with anti–TIF1-gamma dermatomyositis, I would probably manage them differently if I knew that they were CCAR1 positive, because the presence of that additional autoantibody attenuates their cancer risk relative to the general population.”

In an editorial accompanying the study, Manabu Fujimoto, MD, of the department of dermatology at Osaka (Japan) University, commented that it “is of clinical importance in that combination of autoantibodies can predict cancer risk with more accuracy. At the same time, this study will give an insight into the pathomechanisms of how antitumor activity may shape autoimmunity in dermatomyositis.”

It will be “intriguing” to discover whether anti-CCAR1 autoantibodies act only against tumors or might also have an impact on dermatomyositis itself, Dr. Fujimoto said.

The research was supported by grants from the National Institutes of Health; Huayi and Siuling Zhang Discovery Fund; Peter Buck, MD; and the Donald B. and Dorothy L. Stabler Foundation. The authors and Dr. Fujimoto reported no relevant financial relationships.

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

Adults with the inflammatory autoimmune myopathy dermatomyositis are at increased for concurrent cancers, but new research suggests that certain autoantibodies in patients with a specific dermatomyositis subtype may actually protect against cancer.

A study of cohorts of patients with dermatomyositis, other rheumatic diseases, and those without disease showed that among patients with dermatomyositis positive for antitranscriptional intermediary factor 1 (anti–TIF1-gamma) autoantibodies – a disease subtype associated with increased cancer risk – the presence of autoantibodies directed against cell division cycle and apoptosis regulator 1 (CCAR1) was associated with reduced cancer risk “to a level comparable to that seen in the general population,” Christopher A. Mecoli, MD, MHS, of Johns Hopkins University, Baltimore, and colleagues reported.

“Our prior data suggest that there are autoantigens that, when targeted simultaneously with CCAR1, provide additional cancer protection. Although these autoantigens are less frequently targeted, it is likely that additional, more prevalent ‘autoantigen hubs’ remain undiscovered,” they wrote in Arthritis & Rheumatology.

Identification of other autoantibodies both in the anti–TIF1-gamma–positive and other dermatomyositis subgroups may help with cancer risk stratification in patients with the disease and may ultimately improve cancer screening for adults with dermatomyositis, the investigators said.
 

Toward precision medicine

“I think this is a step toward precision medicine in patients with rheumatic disease, specifically myositis,” Dr. Mecoli said in an interview.

The study supports earlier work showing that dermatomyositis and related myopathies are heterogeneous, he said, noting that, “if you put 10 myositis patients in the same room, you wouldn’t get that they all have the same disease because they can look so different from one another.”

The association of dermatomyositis with concurrent cancers has been known for decades, but in recent years his team and other investigators have noted that the association holds true for only some patients with dermatomyositis, most notably those patients positive for anti–TIF1-gamma autoantibodies.

“And then, of course, once you really start studying just one gamma-positive dermatomyositis patient, you realize that even among that group it is heterogeneous in terms of their cancer risk, and that was the main focus of this study: to reconcile this clinical observation that I had a lot of patients with TIF1-gamma dermatomyositis who never get diagnosed with cancer,” Dr. Mecoli said.

Study details

Dr. Dr. Mecoli and colleagues previously reported that immune responses to CCAR1 and other autoantigens seen in patients with dermatomyositis were associated with lower probability of cancer occurrence.

In the current study, they focused on the disease specificity, clinical phenotype, and cancer risk for patients with dermatomyositis and anti-CCAR1 autoantibodies.

They looked at all patients aged 18 or older with a probable or definite finding of dermatomyositis, according to 2017 American College of Rheumatology/European Alliance of Associations for Rheumatology Idiopathic Inflammatory Myopathy criteria, who were seen at Stanford (Calif.) University Medical Center from August 2004 to April 2020 (101 patients), or the Johns Hopkins Myositis Center (141 patients) from January 2007 to December 2020.

Controls included 44 patients evaluated at the Johns Hopkins Myositis Center with immune-mediated necrotizing myopathy, 186 patients with anti–TIF1-gamma–negative dermatomyositis (defined as an enzyme-linked immunosorbent assay readout of less than seven units) evaluated at either Stanford or Johns Hopkins, 44 patients with inclusion body myositis evaluated at Johns Hopkins, and 46 patients with systemic lupus erythematosus from the Hopkins Lupus Cohort. The investigators also assayed serum from 32 healthy individuals.

They found that patients with anti–TIF1-gamma–positive dermatomyositis were significantly more likely than those with anti–TIF1-gamma–negative dermatomyositis to have anti-CCAR1 autoantibodies (32% vs. 8%; P < .001). Additionally, they noted that the anti-CCAR1 autoantibodies were not seen in serum from healthy controls and were found at only very low frequencies among patients with other rheumatic diseases.

When they looked at the incidence of cancer from the time of dermatomyositis onset (defined as the first patient-reported symptoms of rash, weakness, myalgia, or dyspnea) they found that the standardized incidence ratio in anti–TIF1-gamma–positive patients in both the Stanford and Hopkins cohorts was higher than expected, with SIRs of 3.49 and 4.54, respectively (P < .001 for each comparison).

However, among those patients who were both anti–TIF1-gamma positive and anti-CCAR1 positive, the SIRs were 1.78 in the Stanford cohort and 1.61 in the Hopkins cohort, and neither SIR was significantly higher than that of the general population.
 

Risk prediction

Their findings suggest that autoantibody profiles might be used for cancer risk stratification in patients with anti–TIF1-gamma–positive dermatomyositis, Dr. Mecoli said.

“Are we overscreening? What is the cost in terms of patient anxiety, in terms of radiation, and in terms of false positive results?” he asked. “If I had a patient in front of me with anti–TIF1-gamma dermatomyositis, I would probably manage them differently if I knew that they were CCAR1 positive, because the presence of that additional autoantibody attenuates their cancer risk relative to the general population.”

In an editorial accompanying the study, Manabu Fujimoto, MD, of the department of dermatology at Osaka (Japan) University, commented that it “is of clinical importance in that combination of autoantibodies can predict cancer risk with more accuracy. At the same time, this study will give an insight into the pathomechanisms of how antitumor activity may shape autoimmunity in dermatomyositis.”

It will be “intriguing” to discover whether anti-CCAR1 autoantibodies act only against tumors or might also have an impact on dermatomyositis itself, Dr. Fujimoto said.

The research was supported by grants from the National Institutes of Health; Huayi and Siuling Zhang Discovery Fund; Peter Buck, MD; and the Donald B. and Dorothy L. Stabler Foundation. The authors and Dr. Fujimoto reported no relevant financial relationships.

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