SAN DIEGO – The need for antibiotic prophylaxis in dermatologic surgery depends on the type of procedure, the patient, what infection you’re trying to keep at bay, and the type of wound, according to Tissa Hata, MD, professor of dermatology at the University of California, San Diego.

Among the many studies in the medical literature that have examined the use of antibiotics to prevent surgical site infections, one study published in 2006 has the largest number of patients to date, Dr. Hata said at a conference on superficial anatomy and cutaneous surgery sponsored by UCSD and Scripps Clinic. In the prospective study of wound infections in patients undergoing dermatologic surgery without prophylactic antibiotics, researchers in Australia prospectively examined 5,091 lesions, mostly nonmelanoma skin cancers, in 2,424 patients over the course of 3 years.

By procedure, the infection rate was highest for skin grafts (8.70%) and wedge excision of the lip or ear (8.57%), followed by skin flap repairs (2.94%), curettage (0.73%), and simple excision and closure (0.54%). By anatomic site, groin excisional surgery had the highest infection rate (10%), followed by surgical procedures below the knee (6.92%), while those performed on the face had a low rate (0.81%). “Based on their analysis, they suggest antibiotic prophylaxis for all procedures below the knee and groin, wedge excisions of the lip and ear, and all skin grafts,” Dr. Hata said.

In 2008, an advisory statement published in the Journal of the American Academy of Dermatology expanded the procedure location and techniques requiring antibiotic prophylaxis to include procedures on the nose and the lower extremity (especially the leg), and for patients with extensive inflammatory disease. According to the statement, in patients without a penicillin allergy, the suggested antibiotic prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 2 g oral cephalexin or dicloxacillin. In patients with penicillin allergy, the recommended prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin.

In the statement, for patients with no penicillin allergy, the suggested prophylaxis regimen for lesions in the groin or on the lower extremities include 2 g oral cephalexin, 1 tablet of oral trimethoprim/sulfamethoxazole (TMP-SMX) DS, or 500 mg of levofloxacin. In patients with penicillin allergy, the recommended prophylaxis regimen for lesions on the groin and lower extremities is 1 tablet of TMP-SMX DS or 500 mg of levofloxacin.

In 2020, a meta-analysis of surgical site infections in patients undergoing Mohs surgery of the ear and nose found that there was no difference in infections in those locations whether patients received oral antibiotic prophylaxis or not. “But the researchers did not specify the type of closure, whether it was a graft or a flap closure,” Dr. Hata commented.

Endocarditis prophylaxis

Dr. Hata also discussed antibiotic recommendations for endocarditis prophylaxis, noting that the mortality rate from endocarditis is as high as 76%, and an estimated 40% of affected patients require heart valve replacement within 5-8 years. “But the good news is that fewer than 10 cases have been possibly linked to dermatologic procedures,” she said.

During outpatient dermatologic surgery, the incidence of bacteremia is in the range of 1.9%-3%, similar to the incidence of 2% that occurs spontaneously in healthy adults, according to Dr. Hata. She said that the following activities or procedures pose a much higher risk of bacteremia: mastication (17%-24%), tooth brushing (24%-40%), tooth extraction (60%-90%), and incision and drainage of an abscess (38%).

American Heart Association guidelines from 2007 recommend antibiotic prophylaxis in only the highest-risk categories of patients. These guidelines were updated in 2017 to include patients with transcatheter prosthetic valves and those with prosthetic material in valve repair. “The primary reason for revision of guidelines is that endocarditis is much more likely to result from frequent exposure to random bacteremia associated with daily activity such as brushing our teeth or having a tooth extracted,” Dr. Hata explained. “Prophylaxis may prevent an exceedingly small number of cases. Authors of the guidelines concluded that the risk of antibiotic-associated adverse event exceeds the benefit of prophylactic therapy, and that maintenance of optimal oral health is more important than prophylactic antibiotics.”

The 2017 AHA guidelines recommend antibiotic prophylaxis in patients with the following cardiac conditions: those with a prosthetic cardiac valve including transcatheter-implanted prostheses and homografts; those with previous endocarditis; those with prosthetic material used for heart valve repair, such as annuloplasty rings, chords or clips; cardiac transplantation recipients who develop cardiac valvulopathy; and those with certain types of congenital heart disease, including unrepaired cyanotic CHD, a completely repaired congenital heart defect with a prosthetic material or device during the first 6 months after the procedure, and repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device.

Procedures that may require prophylaxis for endocarditis include all dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures that involve incision or biopsy of the respiratory mucosa such as tonsillectomy or adenoidectomy. Antibiotic prophylaxis is not recommended for procedures involving the gastrointestinal tract or the genitourinary tract unless an active infection is present. As for skin procedures, the guidelines recommend antibiotic prophylaxis for patients in the high-risk category who undergo a surgical procedure that involves infected skin, skin structure, or musculoskeletal tissue.

In the 2017 AHA guidelines, patients with no penicillin allergy, the suggested antibiotic prophylaxis regimen for endocarditis in non-oral sites includes 2 g oral cephalexin or dicloxacillin, while in patients with penicillin allergy, the suggested prophylaxis for endocarditis in non-oral sites includes 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin. In patients without a penicillin allergy, the suggested prophylaxis for endocarditis in oral sites is 2 g oral amoxicillin, while in those with penicillin allergy, the suggested antibiotic prophylaxis for endocarditis in oral sites is 500 mg azithromycin/clarithromycin or doxycycline 100 mg.

“Antibiotic prophylaxis for endocarditis should be given 30-60 minutes prior to surgery, and a follow-up dose of antibiotics is no longer recommended,” Dr. Hata said. “If you forget [to administer the antibiotics] or the patient forgets, antibiotics may be given up to 2 hours after the procedure.”

Dr. Hata reported having no relevant disclosures.

SAN DIEGO – The need for antibiotic prophylaxis in dermatologic surgery depends on the type of procedure, the patient, what infection you’re trying to keep at bay, and the type of wound, according to Tissa Hata, MD, professor of dermatology at the University of California, San Diego.

Among the many studies in the medical literature that have examined the use of antibiotics to prevent surgical site infections, one study published in 2006 has the largest number of patients to date, Dr. Hata said at a conference on superficial anatomy and cutaneous surgery sponsored by UCSD and Scripps Clinic. In the prospective study of wound infections in patients undergoing dermatologic surgery without prophylactic antibiotics, researchers in Australia prospectively examined 5,091 lesions, mostly nonmelanoma skin cancers, in 2,424 patients over the course of 3 years.

By procedure, the infection rate was highest for skin grafts (8.70%) and wedge excision of the lip or ear (8.57%), followed by skin flap repairs (2.94%), curettage (0.73%), and simple excision and closure (0.54%). By anatomic site, groin excisional surgery had the highest infection rate (10%), followed by surgical procedures below the knee (6.92%), while those performed on the face had a low rate (0.81%). “Based on their analysis, they suggest antibiotic prophylaxis for all procedures below the knee and groin, wedge excisions of the lip and ear, and all skin grafts,” Dr. Hata said.

In 2008, an advisory statement published in the Journal of the American Academy of Dermatology expanded the procedure location and techniques requiring antibiotic prophylaxis to include procedures on the nose and the lower extremity (especially the leg), and for patients with extensive inflammatory disease. According to the statement, in patients without a penicillin allergy, the suggested antibiotic prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 2 g oral cephalexin or dicloxacillin. In patients with penicillin allergy, the recommended prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin.

In the statement, for patients with no penicillin allergy, the suggested prophylaxis regimen for lesions in the groin or on the lower extremities include 2 g oral cephalexin, 1 tablet of oral trimethoprim/sulfamethoxazole (TMP-SMX) DS, or 500 mg of levofloxacin. In patients with penicillin allergy, the recommended prophylaxis regimen for lesions on the groin and lower extremities is 1 tablet of TMP-SMX DS or 500 mg of levofloxacin.

In 2020, a meta-analysis of surgical site infections in patients undergoing Mohs surgery of the ear and nose found that there was no difference in infections in those locations whether patients received oral antibiotic prophylaxis or not. “But the researchers did not specify the type of closure, whether it was a graft or a flap closure,” Dr. Hata commented.

Endocarditis prophylaxis

Dr. Hata also discussed antibiotic recommendations for endocarditis prophylaxis, noting that the mortality rate from endocarditis is as high as 76%, and an estimated 40% of affected patients require heart valve replacement within 5-8 years. “But the good news is that fewer than 10 cases have been possibly linked to dermatologic procedures,” she said.

During outpatient dermatologic surgery, the incidence of bacteremia is in the range of 1.9%-3%, similar to the incidence of 2% that occurs spontaneously in healthy adults, according to Dr. Hata. She said that the following activities or procedures pose a much higher risk of bacteremia: mastication (17%-24%), tooth brushing (24%-40%), tooth extraction (60%-90%), and incision and drainage of an abscess (38%).

American Heart Association guidelines from 2007 recommend antibiotic prophylaxis in only the highest-risk categories of patients. These guidelines were updated in 2017 to include patients with transcatheter prosthetic valves and those with prosthetic material in valve repair. “The primary reason for revision of guidelines is that endocarditis is much more likely to result from frequent exposure to random bacteremia associated with daily activity such as brushing our teeth or having a tooth extracted,” Dr. Hata explained. “Prophylaxis may prevent an exceedingly small number of cases. Authors of the guidelines concluded that the risk of antibiotic-associated adverse event exceeds the benefit of prophylactic therapy, and that maintenance of optimal oral health is more important than prophylactic antibiotics.”

The 2017 AHA guidelines recommend antibiotic prophylaxis in patients with the following cardiac conditions: those with a prosthetic cardiac valve including transcatheter-implanted prostheses and homografts; those with previous endocarditis; those with prosthetic material used for heart valve repair, such as annuloplasty rings, chords or clips; cardiac transplantation recipients who develop cardiac valvulopathy; and those with certain types of congenital heart disease, including unrepaired cyanotic CHD, a completely repaired congenital heart defect with a prosthetic material or device during the first 6 months after the procedure, and repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device.

Procedures that may require prophylaxis for endocarditis include all dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures that involve incision or biopsy of the respiratory mucosa such as tonsillectomy or adenoidectomy. Antibiotic prophylaxis is not recommended for procedures involving the gastrointestinal tract or the genitourinary tract unless an active infection is present. As for skin procedures, the guidelines recommend antibiotic prophylaxis for patients in the high-risk category who undergo a surgical procedure that involves infected skin, skin structure, or musculoskeletal tissue.

In the 2017 AHA guidelines, patients with no penicillin allergy, the suggested antibiotic prophylaxis regimen for endocarditis in non-oral sites includes 2 g oral cephalexin or dicloxacillin, while in patients with penicillin allergy, the suggested prophylaxis for endocarditis in non-oral sites includes 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin. In patients without a penicillin allergy, the suggested prophylaxis for endocarditis in oral sites is 2 g oral amoxicillin, while in those with penicillin allergy, the suggested antibiotic prophylaxis for endocarditis in oral sites is 500 mg azithromycin/clarithromycin or doxycycline 100 mg.

“Antibiotic prophylaxis for endocarditis should be given 30-60 minutes prior to surgery, and a follow-up dose of antibiotics is no longer recommended,” Dr. Hata said. “If you forget [to administer the antibiotics] or the patient forgets, antibiotics may be given up to 2 hours after the procedure.”

Dr. Hata reported having no relevant disclosures.

SAN DIEGO – The need for antibiotic prophylaxis in dermatologic surgery depends on the type of procedure, the patient, what infection you’re trying to keep at bay, and the type of wound, according to Tissa Hata, MD, professor of dermatology at the University of California, San Diego.

Among the many studies in the medical literature that have examined the use of antibiotics to prevent surgical site infections, one study published in 2006 has the largest number of patients to date, Dr. Hata said at a conference on superficial anatomy and cutaneous surgery sponsored by UCSD and Scripps Clinic. In the prospective study of wound infections in patients undergoing dermatologic surgery without prophylactic antibiotics, researchers in Australia prospectively examined 5,091 lesions, mostly nonmelanoma skin cancers, in 2,424 patients over the course of 3 years.

By procedure, the infection rate was highest for skin grafts (8.70%) and wedge excision of the lip or ear (8.57%), followed by skin flap repairs (2.94%), curettage (0.73%), and simple excision and closure (0.54%). By anatomic site, groin excisional surgery had the highest infection rate (10%), followed by surgical procedures below the knee (6.92%), while those performed on the face had a low rate (0.81%). “Based on their analysis, they suggest antibiotic prophylaxis for all procedures below the knee and groin, wedge excisions of the lip and ear, and all skin grafts,” Dr. Hata said.

In 2008, an advisory statement published in the Journal of the American Academy of Dermatology expanded the procedure location and techniques requiring antibiotic prophylaxis to include procedures on the nose and the lower extremity (especially the leg), and for patients with extensive inflammatory disease. According to the statement, in patients without a penicillin allergy, the suggested antibiotic prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 2 g oral cephalexin or dicloxacillin. In patients with penicillin allergy, the recommended prophylaxis regimen for wedge excision of the lip/ear, flaps on the nose, or all skin grafts include 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin.

In the statement, for patients with no penicillin allergy, the suggested prophylaxis regimen for lesions in the groin or on the lower extremities include 2 g oral cephalexin, 1 tablet of oral trimethoprim/sulfamethoxazole (TMP-SMX) DS, or 500 mg of levofloxacin. In patients with penicillin allergy, the recommended prophylaxis regimen for lesions on the groin and lower extremities is 1 tablet of TMP-SMX DS or 500 mg of levofloxacin.

In 2020, a meta-analysis of surgical site infections in patients undergoing Mohs surgery of the ear and nose found that there was no difference in infections in those locations whether patients received oral antibiotic prophylaxis or not. “But the researchers did not specify the type of closure, whether it was a graft or a flap closure,” Dr. Hata commented.

Endocarditis prophylaxis

Dr. Hata also discussed antibiotic recommendations for endocarditis prophylaxis, noting that the mortality rate from endocarditis is as high as 76%, and an estimated 40% of affected patients require heart valve replacement within 5-8 years. “But the good news is that fewer than 10 cases have been possibly linked to dermatologic procedures,” she said.

During outpatient dermatologic surgery, the incidence of bacteremia is in the range of 1.9%-3%, similar to the incidence of 2% that occurs spontaneously in healthy adults, according to Dr. Hata. She said that the following activities or procedures pose a much higher risk of bacteremia: mastication (17%-24%), tooth brushing (24%-40%), tooth extraction (60%-90%), and incision and drainage of an abscess (38%).

American Heart Association guidelines from 2007 recommend antibiotic prophylaxis in only the highest-risk categories of patients. These guidelines were updated in 2017 to include patients with transcatheter prosthetic valves and those with prosthetic material in valve repair. “The primary reason for revision of guidelines is that endocarditis is much more likely to result from frequent exposure to random bacteremia associated with daily activity such as brushing our teeth or having a tooth extracted,” Dr. Hata explained. “Prophylaxis may prevent an exceedingly small number of cases. Authors of the guidelines concluded that the risk of antibiotic-associated adverse event exceeds the benefit of prophylactic therapy, and that maintenance of optimal oral health is more important than prophylactic antibiotics.”

The 2017 AHA guidelines recommend antibiotic prophylaxis in patients with the following cardiac conditions: those with a prosthetic cardiac valve including transcatheter-implanted prostheses and homografts; those with previous endocarditis; those with prosthetic material used for heart valve repair, such as annuloplasty rings, chords or clips; cardiac transplantation recipients who develop cardiac valvulopathy; and those with certain types of congenital heart disease, including unrepaired cyanotic CHD, a completely repaired congenital heart defect with a prosthetic material or device during the first 6 months after the procedure, and repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device.

Procedures that may require prophylaxis for endocarditis include all dental procedures that involve manipulation of the gingival tissue or the periapical region of teeth or perforation of the oral mucosa, and respiratory tract procedures that involve incision or biopsy of the respiratory mucosa such as tonsillectomy or adenoidectomy. Antibiotic prophylaxis is not recommended for procedures involving the gastrointestinal tract or the genitourinary tract unless an active infection is present. As for skin procedures, the guidelines recommend antibiotic prophylaxis for patients in the high-risk category who undergo a surgical procedure that involves infected skin, skin structure, or musculoskeletal tissue.

In the 2017 AHA guidelines, patients with no penicillin allergy, the suggested antibiotic prophylaxis regimen for endocarditis in non-oral sites includes 2 g oral cephalexin or dicloxacillin, while in patients with penicillin allergy, the suggested prophylaxis for endocarditis in non-oral sites includes 600 mg oral clindamycin or 500 mg oral azithromycin/clarithromycin. In patients without a penicillin allergy, the suggested prophylaxis for endocarditis in oral sites is 2 g oral amoxicillin, while in those with penicillin allergy, the suggested antibiotic prophylaxis for endocarditis in oral sites is 500 mg azithromycin/clarithromycin or doxycycline 100 mg.

“Antibiotic prophylaxis for endocarditis should be given 30-60 minutes prior to surgery, and a follow-up dose of antibiotics is no longer recommended,” Dr. Hata said. “If you forget [to administer the antibiotics] or the patient forgets, antibiotics may be given up to 2 hours after the procedure.”

Dr. Hata reported having no relevant disclosures.

Systemic sclerosis patients with both interstitial lung disease and pulmonary hypertension had worse survival than those without both conditions, based on data from more than 3,000 individuals.

Pulmonary complications are now the most common causes of death in adults with systemic sclerosis (SSc), but the impact of patient characteristics and risk factors such as interstitial lung disease (ILD) and pulmonary hypertension (PH) on SSc outcomes remains unclear, wrote Pia Moinzadeh, MD, of University Hospital Cologne (Germany) and colleagues.

Although the role of ILD and PH in different SSc subtypes has been studied, larger studies of the effects of ILD and combining ILD and PH on outcomes are needed, since survival rates can change over time with new classification criteria, diagnostic tools, and improved therapies, they said.

In a study published in the journal Chest, the researchers reviewed data from 3,257 adults aged 18 years and older with SSc over a mean follow-up of 3.45 years. Participants were part of the German Network for Systemic Sclerosis (DNSS) that included 25 clinical centers in Germany. The participants were divided into SSc subsets: 54.2% with limited cutaneous SSc (lcSSc), 31.4% with diffuse cutaneous SSc (dcSSc), and 14.4% SSc overlapping syndromes.

The baseline prevalence of ILD was 34.5%, including 200 patients with ILD-PH and 923 with ILD but without PH. The baseline prevalence of PH without ILD was 4.5%. ILD was defined as SSc associated when other causes were excluded. PH was defined as an increase in mean arterial pressure of at least 25 mm Hg at rest, and also was defined by an estimated right ventricular systolic pressure greater than 35 mm Hg based on echocardiography.

By the end of the study period, 47.6% of SSc patients had ILD, 15.2% had ILD-PH, and 6.5% had pulmonary arterial hypertension (PAH). Of the SSc patients with ILD, 57.3% had dcSSc; the prevalence of PAH was not significantly different between the SSc subtypes. Patients with dcSSc were more likely to develop ILD-PH (52.2%) and ILD without PH (52.1%); patients with lcSSc were more likely to have PAH (64.9%) or no pulmonary involvement (64.1%).

“For all subsets, a significant increase in the frequency of SSc-ILD was observed during follow-ups,” the researchers noted.

Overall survival at 5 years was worst for patients with both ILD and PH (79.1%). Five-year OS for patients with PAH was 85.0%. OS at 5 years was significantly better for patients with ILD without PH (92.8%) and those with no pulmonary involvement (96.4%), compared with the ILD and PH patients (P < 0.001).

In a multivariate analysis, the risk of death was more than five times higher for patients with ILD-PH, compared with the reference group of patients without pulmonary involvement (hazard ratio, 5.3). Factors associated with reduced risk of death included female sex (HR, 0.3), higher body mass index (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide (HR, 0.98).

The findings were limited by several factors including the incomplete data for patients enrolled early in the registry, lack of complete radiology data, and the inability to determine whether the association between pulmonary involvement and survival was related to ILD or to pulmonary vascular disease, the researchers noted.

However, the results suggest that a combination of ILD and PH is the main predictor of death in patients with SSc and ILD, although the overall survival for SSc patients with and without pulmonary involvement has improved in recent decades thanks to improved therapies, multidisciplinary care, and greater attention to the disease worldwide, they concluded.

The study received no outside funding. Dr. Moinzadeh disclosed lecture fees from Boehringer Ingelheim.

Systemic sclerosis patients with both interstitial lung disease and pulmonary hypertension had worse survival than those without both conditions, based on data from more than 3,000 individuals.

Pulmonary complications are now the most common causes of death in adults with systemic sclerosis (SSc), but the impact of patient characteristics and risk factors such as interstitial lung disease (ILD) and pulmonary hypertension (PH) on SSc outcomes remains unclear, wrote Pia Moinzadeh, MD, of University Hospital Cologne (Germany) and colleagues.

Although the role of ILD and PH in different SSc subtypes has been studied, larger studies of the effects of ILD and combining ILD and PH on outcomes are needed, since survival rates can change over time with new classification criteria, diagnostic tools, and improved therapies, they said.

In a study published in the journal Chest, the researchers reviewed data from 3,257 adults aged 18 years and older with SSc over a mean follow-up of 3.45 years. Participants were part of the German Network for Systemic Sclerosis (DNSS) that included 25 clinical centers in Germany. The participants were divided into SSc subsets: 54.2% with limited cutaneous SSc (lcSSc), 31.4% with diffuse cutaneous SSc (dcSSc), and 14.4% SSc overlapping syndromes.

The baseline prevalence of ILD was 34.5%, including 200 patients with ILD-PH and 923 with ILD but without PH. The baseline prevalence of PH without ILD was 4.5%. ILD was defined as SSc associated when other causes were excluded. PH was defined as an increase in mean arterial pressure of at least 25 mm Hg at rest, and also was defined by an estimated right ventricular systolic pressure greater than 35 mm Hg based on echocardiography.

By the end of the study period, 47.6% of SSc patients had ILD, 15.2% had ILD-PH, and 6.5% had pulmonary arterial hypertension (PAH). Of the SSc patients with ILD, 57.3% had dcSSc; the prevalence of PAH was not significantly different between the SSc subtypes. Patients with dcSSc were more likely to develop ILD-PH (52.2%) and ILD without PH (52.1%); patients with lcSSc were more likely to have PAH (64.9%) or no pulmonary involvement (64.1%).

“For all subsets, a significant increase in the frequency of SSc-ILD was observed during follow-ups,” the researchers noted.

Overall survival at 5 years was worst for patients with both ILD and PH (79.1%). Five-year OS for patients with PAH was 85.0%. OS at 5 years was significantly better for patients with ILD without PH (92.8%) and those with no pulmonary involvement (96.4%), compared with the ILD and PH patients (P < 0.001).

In a multivariate analysis, the risk of death was more than five times higher for patients with ILD-PH, compared with the reference group of patients without pulmonary involvement (hazard ratio, 5.3). Factors associated with reduced risk of death included female sex (HR, 0.3), higher body mass index (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide (HR, 0.98).

The findings were limited by several factors including the incomplete data for patients enrolled early in the registry, lack of complete radiology data, and the inability to determine whether the association between pulmonary involvement and survival was related to ILD or to pulmonary vascular disease, the researchers noted.

However, the results suggest that a combination of ILD and PH is the main predictor of death in patients with SSc and ILD, although the overall survival for SSc patients with and without pulmonary involvement has improved in recent decades thanks to improved therapies, multidisciplinary care, and greater attention to the disease worldwide, they concluded.

The study received no outside funding. Dr. Moinzadeh disclosed lecture fees from Boehringer Ingelheim.

Systemic sclerosis patients with both interstitial lung disease and pulmonary hypertension had worse survival than those without both conditions, based on data from more than 3,000 individuals.

Pulmonary complications are now the most common causes of death in adults with systemic sclerosis (SSc), but the impact of patient characteristics and risk factors such as interstitial lung disease (ILD) and pulmonary hypertension (PH) on SSc outcomes remains unclear, wrote Pia Moinzadeh, MD, of University Hospital Cologne (Germany) and colleagues.

Although the role of ILD and PH in different SSc subtypes has been studied, larger studies of the effects of ILD and combining ILD and PH on outcomes are needed, since survival rates can change over time with new classification criteria, diagnostic tools, and improved therapies, they said.

In a study published in the journal Chest, the researchers reviewed data from 3,257 adults aged 18 years and older with SSc over a mean follow-up of 3.45 years. Participants were part of the German Network for Systemic Sclerosis (DNSS) that included 25 clinical centers in Germany. The participants were divided into SSc subsets: 54.2% with limited cutaneous SSc (lcSSc), 31.4% with diffuse cutaneous SSc (dcSSc), and 14.4% SSc overlapping syndromes.

The baseline prevalence of ILD was 34.5%, including 200 patients with ILD-PH and 923 with ILD but without PH. The baseline prevalence of PH without ILD was 4.5%. ILD was defined as SSc associated when other causes were excluded. PH was defined as an increase in mean arterial pressure of at least 25 mm Hg at rest, and also was defined by an estimated right ventricular systolic pressure greater than 35 mm Hg based on echocardiography.

By the end of the study period, 47.6% of SSc patients had ILD, 15.2% had ILD-PH, and 6.5% had pulmonary arterial hypertension (PAH). Of the SSc patients with ILD, 57.3% had dcSSc; the prevalence of PAH was not significantly different between the SSc subtypes. Patients with dcSSc were more likely to develop ILD-PH (52.2%) and ILD without PH (52.1%); patients with lcSSc were more likely to have PAH (64.9%) or no pulmonary involvement (64.1%).

“For all subsets, a significant increase in the frequency of SSc-ILD was observed during follow-ups,” the researchers noted.

Overall survival at 5 years was worst for patients with both ILD and PH (79.1%). Five-year OS for patients with PAH was 85.0%. OS at 5 years was significantly better for patients with ILD without PH (92.8%) and those with no pulmonary involvement (96.4%), compared with the ILD and PH patients (P < 0.001).

In a multivariate analysis, the risk of death was more than five times higher for patients with ILD-PH, compared with the reference group of patients without pulmonary involvement (hazard ratio, 5.3). Factors associated with reduced risk of death included female sex (HR, 0.3), higher body mass index (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide (HR, 0.98).

The findings were limited by several factors including the incomplete data for patients enrolled early in the registry, lack of complete radiology data, and the inability to determine whether the association between pulmonary involvement and survival was related to ILD or to pulmonary vascular disease, the researchers noted.

However, the results suggest that a combination of ILD and PH is the main predictor of death in patients with SSc and ILD, although the overall survival for SSc patients with and without pulmonary involvement has improved in recent decades thanks to improved therapies, multidisciplinary care, and greater attention to the disease worldwide, they concluded.

The study received no outside funding. Dr. Moinzadeh disclosed lecture fees from Boehringer Ingelheim.

Written exposure therapy (WET) for posttraumatic stress disorder was just as effective as prolonged exposure therapy (PE), results of a new randomized clinical trial show.

Investigators also found that participants randomly assigned to receive WET were significantly less likely to drop out of treatment than those receiving PE.

Written exposure therapy involves writing about thoughts and feelings during a specific traumatic event during five supervised, 30-minute sessions and discussing the writing process with the therapist supervising the sessions.

In the latter sessions, the participant talks about how the event affected them.

“Clinicians should consider using WET in their practices as some clients would prefer a shorter treatment approach, and it may be the only option for some clients – for instance, those who have limited time for therapy and may not be able to do a longer treatment,” study investigator Denise Sloan, PhD, said in an interview.

She also noted that WET is covered by insurance and that “most providers I know indicate that they list it as CBT [cognitive-behavioral therapy] code to insurance companies.”

Sloan is senior clinician investigator of the National Center for PTSD at VA Boston Healthcare System and professor of psychiatry at Boston University.

The findings were published online in JAMA Psychiatry.
 

High attrition rates

The disadvantage to the three major types of therapy used most often to treat PTSD in veterans – eye movement desensitization and reprocessing, cognitive processing therapy (CPT), and PE – are the dropout rates, that range from 18% to as high as 50%.

Prior studies have shown that WET is briefer and just as effective as CPT, but investigators noted that it had never been tested against PE in a randomized clinical trial.

To find out how the two types of therapy compare, Dr. Sloan and associates randomized 178 veterans with PTSD from three VA centers – Boston; Charleston, S.C.; and Madison, Wisc. – to receive either WET or PE.

PE consisted of 8-15 90-minute therapy sessions during which participants imagine the most distressing aspect of their traumatic memory, and between sessions, they confront the people, places, or situations they have been avoiding because of the trauma.

The investigators used the Structured Clinical Interview for DSM-5 at baseline to screen participants at high risk for suicide, comorbid substance use disorder, and unstable bipolar disorder, who were excluded from the study.

At baseline, 10, 20, and 30 weeks after the first treatment session, the investigators measured the severity of each patient’s PTSD symptoms with the Clinician-Administered PTSD Scale for DSM-5, which has a range of 0 (no PTSD symptoms) to 80 (most severe PTSD symptoms).

Of the 178 veterans, 134 were men, and their mean age was 45 years. The majority (63%) was White, while 21% were Black.

The researchers found that study participants were not significantly more likely to meet PTSD diagnostic criteria in the WET or PE conditions at any assessment.
 

WET briefer, better retention

Investigators noted the largest difference in PTSD scores in favor of WET at the 10-month assessment: The mean score for those receiving WET was 27.7, and the mean score for those receiving PE was 30.1 (odds ratio, 0.72; 95% CI, 0.35-1.46).

Among those who finished treatment, the mean number of treatment sessions was 12.5 for PE and 6 for WET.

Participants assigned to receive PE were significantly more likely to drop out of the study prematurely; 32 (35.6%) dropped out, compared with 11 (12.5%) participants assigned to WET.

Notably, of the 32 participants who dropped out of PE, 30 did so by session 7, so the increased dropout in PE was not related to the greater number of sessions, the investigators noted.

They added that findings could have been limited by stressors related to the global COVID-19 pandemic, which was taking place during the treatment, and the fact that all of the participants were veterans, which could limit the generalizability of the findings.

In an editorial, Charles Taylor, PhD, and Murray Stein, MD, MPH, both from the department of psychiatry at the University of California, San Diego, wrote that “WET achieved comparable reductions in PTSD symptoms through fewer sessions, shorter duration sessions, less therapist involvement, and no explicit prescription of homework.

“These findings should galvanize the psychotherapy field to design parsimonious treatments from the start, systematically testing the effects of different dose parameters,” they concluded.

The study was supported by the VA. Dr. Sloan reported receiving royalty payments for the published Written Exposure Therapy manual from the American Psychological Association outside the submitted work.

A version of this article appeared on Medscape.com.

Written exposure therapy (WET) for posttraumatic stress disorder was just as effective as prolonged exposure therapy (PE), results of a new randomized clinical trial show.

Investigators also found that participants randomly assigned to receive WET were significantly less likely to drop out of treatment than those receiving PE.

Written exposure therapy involves writing about thoughts and feelings during a specific traumatic event during five supervised, 30-minute sessions and discussing the writing process with the therapist supervising the sessions.

In the latter sessions, the participant talks about how the event affected them.

“Clinicians should consider using WET in their practices as some clients would prefer a shorter treatment approach, and it may be the only option for some clients – for instance, those who have limited time for therapy and may not be able to do a longer treatment,” study investigator Denise Sloan, PhD, said in an interview.

She also noted that WET is covered by insurance and that “most providers I know indicate that they list it as CBT [cognitive-behavioral therapy] code to insurance companies.”

Sloan is senior clinician investigator of the National Center for PTSD at VA Boston Healthcare System and professor of psychiatry at Boston University.

The findings were published online in JAMA Psychiatry.
 

High attrition rates

The disadvantage to the three major types of therapy used most often to treat PTSD in veterans – eye movement desensitization and reprocessing, cognitive processing therapy (CPT), and PE – are the dropout rates, that range from 18% to as high as 50%.

Prior studies have shown that WET is briefer and just as effective as CPT, but investigators noted that it had never been tested against PE in a randomized clinical trial.

To find out how the two types of therapy compare, Dr. Sloan and associates randomized 178 veterans with PTSD from three VA centers – Boston; Charleston, S.C.; and Madison, Wisc. – to receive either WET or PE.

PE consisted of 8-15 90-minute therapy sessions during which participants imagine the most distressing aspect of their traumatic memory, and between sessions, they confront the people, places, or situations they have been avoiding because of the trauma.

The investigators used the Structured Clinical Interview for DSM-5 at baseline to screen participants at high risk for suicide, comorbid substance use disorder, and unstable bipolar disorder, who were excluded from the study.

At baseline, 10, 20, and 30 weeks after the first treatment session, the investigators measured the severity of each patient’s PTSD symptoms with the Clinician-Administered PTSD Scale for DSM-5, which has a range of 0 (no PTSD symptoms) to 80 (most severe PTSD symptoms).

Of the 178 veterans, 134 were men, and their mean age was 45 years. The majority (63%) was White, while 21% were Black.

The researchers found that study participants were not significantly more likely to meet PTSD diagnostic criteria in the WET or PE conditions at any assessment.
 

WET briefer, better retention

Investigators noted the largest difference in PTSD scores in favor of WET at the 10-month assessment: The mean score for those receiving WET was 27.7, and the mean score for those receiving PE was 30.1 (odds ratio, 0.72; 95% CI, 0.35-1.46).

Among those who finished treatment, the mean number of treatment sessions was 12.5 for PE and 6 for WET.

Participants assigned to receive PE were significantly more likely to drop out of the study prematurely; 32 (35.6%) dropped out, compared with 11 (12.5%) participants assigned to WET.

Notably, of the 32 participants who dropped out of PE, 30 did so by session 7, so the increased dropout in PE was not related to the greater number of sessions, the investigators noted.

They added that findings could have been limited by stressors related to the global COVID-19 pandemic, which was taking place during the treatment, and the fact that all of the participants were veterans, which could limit the generalizability of the findings.

In an editorial, Charles Taylor, PhD, and Murray Stein, MD, MPH, both from the department of psychiatry at the University of California, San Diego, wrote that “WET achieved comparable reductions in PTSD symptoms through fewer sessions, shorter duration sessions, less therapist involvement, and no explicit prescription of homework.

“These findings should galvanize the psychotherapy field to design parsimonious treatments from the start, systematically testing the effects of different dose parameters,” they concluded.

The study was supported by the VA. Dr. Sloan reported receiving royalty payments for the published Written Exposure Therapy manual from the American Psychological Association outside the submitted work.

A version of this article appeared on Medscape.com.

Written exposure therapy (WET) for posttraumatic stress disorder was just as effective as prolonged exposure therapy (PE), results of a new randomized clinical trial show.

Investigators also found that participants randomly assigned to receive WET were significantly less likely to drop out of treatment than those receiving PE.

Written exposure therapy involves writing about thoughts and feelings during a specific traumatic event during five supervised, 30-minute sessions and discussing the writing process with the therapist supervising the sessions.

In the latter sessions, the participant talks about how the event affected them.

“Clinicians should consider using WET in their practices as some clients would prefer a shorter treatment approach, and it may be the only option for some clients – for instance, those who have limited time for therapy and may not be able to do a longer treatment,” study investigator Denise Sloan, PhD, said in an interview.

She also noted that WET is covered by insurance and that “most providers I know indicate that they list it as CBT [cognitive-behavioral therapy] code to insurance companies.”

Sloan is senior clinician investigator of the National Center for PTSD at VA Boston Healthcare System and professor of psychiatry at Boston University.

The findings were published online in JAMA Psychiatry.
 

High attrition rates

The disadvantage to the three major types of therapy used most often to treat PTSD in veterans – eye movement desensitization and reprocessing, cognitive processing therapy (CPT), and PE – are the dropout rates, that range from 18% to as high as 50%.

Prior studies have shown that WET is briefer and just as effective as CPT, but investigators noted that it had never been tested against PE in a randomized clinical trial.

To find out how the two types of therapy compare, Dr. Sloan and associates randomized 178 veterans with PTSD from three VA centers – Boston; Charleston, S.C.; and Madison, Wisc. – to receive either WET or PE.

PE consisted of 8-15 90-minute therapy sessions during which participants imagine the most distressing aspect of their traumatic memory, and between sessions, they confront the people, places, or situations they have been avoiding because of the trauma.

The investigators used the Structured Clinical Interview for DSM-5 at baseline to screen participants at high risk for suicide, comorbid substance use disorder, and unstable bipolar disorder, who were excluded from the study.

At baseline, 10, 20, and 30 weeks after the first treatment session, the investigators measured the severity of each patient’s PTSD symptoms with the Clinician-Administered PTSD Scale for DSM-5, which has a range of 0 (no PTSD symptoms) to 80 (most severe PTSD symptoms).

Of the 178 veterans, 134 were men, and their mean age was 45 years. The majority (63%) was White, while 21% were Black.

The researchers found that study participants were not significantly more likely to meet PTSD diagnostic criteria in the WET or PE conditions at any assessment.
 

WET briefer, better retention

Investigators noted the largest difference in PTSD scores in favor of WET at the 10-month assessment: The mean score for those receiving WET was 27.7, and the mean score for those receiving PE was 30.1 (odds ratio, 0.72; 95% CI, 0.35-1.46).

Among those who finished treatment, the mean number of treatment sessions was 12.5 for PE and 6 for WET.

Participants assigned to receive PE were significantly more likely to drop out of the study prematurely; 32 (35.6%) dropped out, compared with 11 (12.5%) participants assigned to WET.

Notably, of the 32 participants who dropped out of PE, 30 did so by session 7, so the increased dropout in PE was not related to the greater number of sessions, the investigators noted.

They added that findings could have been limited by stressors related to the global COVID-19 pandemic, which was taking place during the treatment, and the fact that all of the participants were veterans, which could limit the generalizability of the findings.

In an editorial, Charles Taylor, PhD, and Murray Stein, MD, MPH, both from the department of psychiatry at the University of California, San Diego, wrote that “WET achieved comparable reductions in PTSD symptoms through fewer sessions, shorter duration sessions, less therapist involvement, and no explicit prescription of homework.

“These findings should galvanize the psychotherapy field to design parsimonious treatments from the start, systematically testing the effects of different dose parameters,” they concluded.

The study was supported by the VA. Dr. Sloan reported receiving royalty payments for the published Written Exposure Therapy manual from the American Psychological Association outside the submitted work.

A version of this article appeared on Medscape.com.

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

The largest study to date of chronic traumatic encephalopathy (CTE) in young athletes shows that 41% had the neurodegenerative disease, caused by repetitive head impacts (RHIs).

Analysis of brain tissue from athletes who were exposed to RHIs and died before the age of 30 revealed neuropathological evidence of shrinkage of the brain and microscopic changes that indicate a breach of the blood-brain barrier. The case series also identified the first known American female athlete with CTE.

Nearly all of those with CTE had a mild form of the disease and 71% played only at the amateur level in youth, high school, or college sports.

“A lot of people think CTE is a result of high-level, professional play such as football, ice hockey, and boxing, but it can affect amateur athletes and can affect people at a young age,” lead author Ann McKee, MD, professor of neurology and pathology and director of the Chronic Traumatic Encephalopathy Center at Boston University, said in an interview.

The findings were published online in JAMA Neurology.
 

A rare look

Brain donation at younger ages is rare, so most of what is known about CTE comes from studies in older athletes.

“We’ve always known that young people could develop this disease early after just amateur high school, youth, and college exposure, but this is the largest study of donor brains at this age,” Dr. McKee said.

The case series included 152 brains of athletes who played contact sports, experienced RHIs, and died before age 30. The tissues are part of the Understanding Neurologic Injury and Traumatic Encephalopathy (UNITE) Brain Bank and were donated between February 2008 and September 2022.

Researchers reviewed the donors’ medical records and conducted retrospective interviews with the donors’ next of kin to assess cognitive symptoms, mood disturbances, and neurobehavioral issues.

Donors died between the ages of 13 and 29 years, 92.8% were male and 73% were White. In 57.2% of the cases, suicide was the cause of death, with no difference between those with or without CTE.

CTE was neuropathologically diagnosed in 41.4% of athletes, using diagnostic criteria developed by the National Institute of Neurological Disorders and Stroke. 

More than 95% had mild CTE. Diagnosis was associated with older age (mean difference, 3.92 years; P < .001) and significantly more years of exposure to contact sports (11.6 vs. 8.8 years).

Among those with CTE, 71.4% played amateur sports, including football (60.9%), soccer (17.2%), hockey (7.8%), and wrestling (7%).

The cohort includes the first known American female athlete with CTE. Recruiting female brain donors has always been a challenge, Dr. McKee said. In this study, females comprised about 7% of the entire cohort and tended to be younger and play fewer years of a sport, compared with their male counterparts. All of that could lower their risk for CTE, Dr. McKee said.

“We don’t have enough brain donations to make any comments about differences between the genders, but we’ve always known that women can develop CTE,” she said. “It’s been reported after domestic violence and in an autistic woman who was a headbanger, so it was just a matter of time before we found our first case.”
 

Early stage of CTE?

Neuropathological analysis revealed neuronal p-tau aggregates in all CTE cases, a hallmark of the disease.

Young athletes with CTE had significantly more ventricular dilatation, suggesting atrophy or shrinkage of the brain, and more cavum septum pellucidum.

“I was surprised that even at this very young age group we could see structural changes to the gross pathology,” Dr. McKee said.

Investigators also found evidence of perivascular macrophages in the deep white matter, a microscopic change that correlated with CTE and years of play and indicates a breach of the blood-brain barrier that could allow pro-inflammatory molecules to enter the brain, setting up a neuroinflammatory response.

“Neuroinflammation is a very early change after repetitive head impacts, as well as in CTE,” Dr. McKee said. “This may be one of the mechanisms by which the inflammation starts, meaning microvascular injury might be an integral part of the pathogenesis of CTE.”
 

A message for clinicians

All athletes had symptoms of mood and neurobehavioral dysfunction common in people with RHIs. There were no significant differences in those clinical symptoms based on CTE diagnosis, which is likely related to the retrospective nature of the clinical evaluations, Dr. McKee said.

While the study leaves many questions about CTE in younger athletes unanswered, there is a message for clinicians and for patients in the findings, she said.

For clinicians, it’s important to note that “this young population of amateur athletes can be very symptomatic, and in all likelihood, a lot of these symptoms are reversible with proper care and management,” Dr. McKee said.

“For individual athletes, it’s important to note that 58% of this cohort did not have CTE, so just because you have these symptoms is not an indication that you have a neurodegenerative disease,” she added.

The study was funded by Andlinger Foundation, the National Football League, Mac Parkman Foundation, National Operating Committee on Standards for Athletic Equipment, and the Nick and Lynn Buoniconti Foundation, World Wrestling Entertainment, Alzheimer’s Association, National Institutes of Health, Concussion Legacy Foundation, U.S. Department of Defense and the U.S. Department of Veterans Affairs. Dr. McKee is a member of the Mackey-White Health and Safety Committee of the National Football League Players Association and reported receiving grants from the NIH and Department of Veteran Affairs and other funding from the Buoniconti Foundation and Mac Parkman Foundation during the conduct of the study.

A version of this article appeared on Medscape.com.

Catheter ablation had long taken atrial fibrillation (AF) rhythm control to the next level before clinical trials showed it could help keep AF patients with heart failure (HF) alive and out of the hospital.

But those trials didn’t include many patients with AF on top of advanced or even end-stage HF. Lacking much of an evidence base and often viewed as too sick to gain a lot from the procedure, patients with AF and advanced HF aren’t offered ablation very often.

Now a randomized trial suggests that, on the contrary, AF ablation may confer a similar benefit to patients with HF so advanced that they were referred for evaluation at a transplant center.

The study, modestly sized with fewer than 200 such patients and conducted at a single center, assigned half of them to receive ablation and the other half to continued medical management.

Risk for the composite primary endpoint plunged 76% over a median of 18 months for those who underwent ablation. The outcome comprised death from any cause, implantation of a left ventricular assist device (LVAD), or urgent heart transplantation.

The advantage for ablation emerged early enough that the trial, CASTLE-HTx, was halted for benefit only a year after reaching its planned enrollment, observed Christian Sohns, MD, when formally presenting the results in Amsterdam at the annual congress of the European Society of Cardiology.

The difference in the primary endpoint “in this severely sick cohort of advanced, end-stage heart failure patients,” he said, was driven mostly by fewer deaths, especially cardiovascular deaths, in the ablation group.

Ablation’s effect on outcomes was associated, perhaps causally, with significant gains in left ventricular (LV) function and more than triple the reduction in AF burden seen in the control group, noted Dr. Sohns, from the Heart and Diabetes Center North-Rhine Westphalia, Bad Oeynhausen, Germany.

“Our trial suggests that in patients with atrial fibrillation and end-stage heart failure, catheter ablation may ameliorate the clinical course,” states the CASTLE-HTx primary report, published in the New England Journal of Medicine, with Dr. Sohns as lead author, in tandem with his ESC presentation.

One of the study’s key messages “is that AF ablation is safe and effective in patients with end-stage heart failure” and “should be part of our armamentarium” for treating them, said Philipp Sommer, MD, also with Heart and Diabetes Center North-Rhine Westphalia, at a press conference preceding Dr. Sohns’ presentation of CASTLE-HTx.

The intervention could potentially help such patients survive longer on transplant wait lists and even delay need for the surgery, proposed Dr. Sommer, who is senior author on the trial’s publication.

CASTLE-HTx suggests that patients with advanced HF and even persistent AF, “if they have reasonably small atria, should be actually considered for ablation, as it may prevent the need for heart transplant or LVAD implant,” said invited discussant Finn Gustafsson, MD, PhD, DMSc, after Dr. Sohns’ presentation. “And that, of course, would be a huge achievement.”

The trial “should, if anything, help eradicate the current somewhat nihilistic approach to atrial fibrillation management in patients with advanced heart failure,” said Dr. Gustafsson, medical director of cardiac transplantation and mechanical circulatory support, Rigshopsitalet Copenhagen University Hospital.

Still, he disputed the characterization by the investigators and indeed the published report that the patients, or most of them, had “end-stage heart failure.”

For example, about a third of the trial’s patients started out in NYHA class 2, Dr. Gustafsson noted. Not that they weren’t “high-risk” or their HF wasn’t severe, he offered, but they don’t seem to have been “a truly advanced heart failure population.”

The trial population consisted of “patients referred to an advanced heart failure center, rather than patients with advanced heart failure,” agreed Mandeep R. Mehra, MD, director of the Center for Advanced Heart Disease at Brigham and Woman’s Hospital, Boston.

Also citing a large prevalence of patients in NYHA class-2, Dr. Mehra added that “we almost never see paroxysmal atrial fib in these patients. It’s usually an early-stage phenomenon.” In advanced HF, AF “is usually permanent,” he told this news organization. Yet it was paroxysmal in about 30% of cases.

To its credit, Dr. Mehra observed, the study does assert that advanced HF is no reason, necessarily, to avoid catheter ablation. Nor should an AF patient’s referral to an advanced-HF center “mean that you should rush to an LVAD or transplant” before considering ablation.

The study seems to be saying, “please exhaust all options before you biologically replace the heart or put in an LVAD,” Dr. Mehra said. “Certainly, this paper steers you in that direction.”

The trial entered 194 patients with symptomatic AF and HF of at least NYHA class 2, with impaired functional capacity by the 6-minute walk test, who had been referred to a major center in Germany for a heart-transplantation workup. With all on guideline-directed medical therapy, 97 were randomly assigned open-label to catheter ablation and 97 to continued standard care.

Catheter ablation was actually carried out in 81 patients (84%) who had been assigned to it and in 16 (16%) of those in the control group, the report states.

A total of 8 in the ablation group and 29 in the control arm died, received an LVAD, or went to urgent transplantation, for a hazard ratio of 0.24 (95% confidence interval, 0.11-0.52; P < .001) for the primary endpoint.

Death from any cause apparently played a big role in the risk reduction; its HR was 0.29 (95% CI, 0.12-0.72).

One peculiarity of the data, Dr. Mehra said, is that event curves for the primary endpoint and its individual components “diverge almost from day 1.” That would mean the ablation group right away started having fewer deaths, LVAD placements, or heart transplants than the control group.

“It is surprising to see such a large effect size on endpoints that are very much dependent on operators and diverge within the first day.” Probably, Dr. Mehra said, “it has to do with this being a single-center study that may not be generalizable to other practices.”

CASTLE HTx was supported by a grant from Else Kröner-Fresenius-Stiftung. Dr. Sommer discloses consulting for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr. Sohns reported no relevant financial relationships. Dr. Gustafsson discloses receiving honoraria or fees for consulting from Abbott, Alnylam Amgen, Boehringer Ingelheim, Ionis, Novartis, and Pfizer; serving on a speakers bureau for Astra Zeneca and Orion; and receiving grants from Corvia Research. Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board for NuPulseCV, Leviticus, and FineHeart.

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

Catheter ablation had long taken atrial fibrillation (AF) rhythm control to the next level before clinical trials showed it could help keep AF patients with heart failure (HF) alive and out of the hospital.

But those trials didn’t include many patients with AF on top of advanced or even end-stage HF. Lacking much of an evidence base and often viewed as too sick to gain a lot from the procedure, patients with AF and advanced HF aren’t offered ablation very often.

Now a randomized trial suggests that, on the contrary, AF ablation may confer a similar benefit to patients with HF so advanced that they were referred for evaluation at a transplant center.

The study, modestly sized with fewer than 200 such patients and conducted at a single center, assigned half of them to receive ablation and the other half to continued medical management.

Risk for the composite primary endpoint plunged 76% over a median of 18 months for those who underwent ablation. The outcome comprised death from any cause, implantation of a left ventricular assist device (LVAD), or urgent heart transplantation.

The advantage for ablation emerged early enough that the trial, CASTLE-HTx, was halted for benefit only a year after reaching its planned enrollment, observed Christian Sohns, MD, when formally presenting the results in Amsterdam at the annual congress of the European Society of Cardiology.

The difference in the primary endpoint “in this severely sick cohort of advanced, end-stage heart failure patients,” he said, was driven mostly by fewer deaths, especially cardiovascular deaths, in the ablation group.

Ablation’s effect on outcomes was associated, perhaps causally, with significant gains in left ventricular (LV) function and more than triple the reduction in AF burden seen in the control group, noted Dr. Sohns, from the Heart and Diabetes Center North-Rhine Westphalia, Bad Oeynhausen, Germany.

“Our trial suggests that in patients with atrial fibrillation and end-stage heart failure, catheter ablation may ameliorate the clinical course,” states the CASTLE-HTx primary report, published in the New England Journal of Medicine, with Dr. Sohns as lead author, in tandem with his ESC presentation.

One of the study’s key messages “is that AF ablation is safe and effective in patients with end-stage heart failure” and “should be part of our armamentarium” for treating them, said Philipp Sommer, MD, also with Heart and Diabetes Center North-Rhine Westphalia, at a press conference preceding Dr. Sohns’ presentation of CASTLE-HTx.

The intervention could potentially help such patients survive longer on transplant wait lists and even delay need for the surgery, proposed Dr. Sommer, who is senior author on the trial’s publication.

CASTLE-HTx suggests that patients with advanced HF and even persistent AF, “if they have reasonably small atria, should be actually considered for ablation, as it may prevent the need for heart transplant or LVAD implant,” said invited discussant Finn Gustafsson, MD, PhD, DMSc, after Dr. Sohns’ presentation. “And that, of course, would be a huge achievement.”

The trial “should, if anything, help eradicate the current somewhat nihilistic approach to atrial fibrillation management in patients with advanced heart failure,” said Dr. Gustafsson, medical director of cardiac transplantation and mechanical circulatory support, Rigshopsitalet Copenhagen University Hospital.

Still, he disputed the characterization by the investigators and indeed the published report that the patients, or most of them, had “end-stage heart failure.”

For example, about a third of the trial’s patients started out in NYHA class 2, Dr. Gustafsson noted. Not that they weren’t “high-risk” or their HF wasn’t severe, he offered, but they don’t seem to have been “a truly advanced heart failure population.”

The trial population consisted of “patients referred to an advanced heart failure center, rather than patients with advanced heart failure,” agreed Mandeep R. Mehra, MD, director of the Center for Advanced Heart Disease at Brigham and Woman’s Hospital, Boston.

Also citing a large prevalence of patients in NYHA class-2, Dr. Mehra added that “we almost never see paroxysmal atrial fib in these patients. It’s usually an early-stage phenomenon.” In advanced HF, AF “is usually permanent,” he told this news organization. Yet it was paroxysmal in about 30% of cases.

To its credit, Dr. Mehra observed, the study does assert that advanced HF is no reason, necessarily, to avoid catheter ablation. Nor should an AF patient’s referral to an advanced-HF center “mean that you should rush to an LVAD or transplant” before considering ablation.

The study seems to be saying, “please exhaust all options before you biologically replace the heart or put in an LVAD,” Dr. Mehra said. “Certainly, this paper steers you in that direction.”

The trial entered 194 patients with symptomatic AF and HF of at least NYHA class 2, with impaired functional capacity by the 6-minute walk test, who had been referred to a major center in Germany for a heart-transplantation workup. With all on guideline-directed medical therapy, 97 were randomly assigned open-label to catheter ablation and 97 to continued standard care.

Catheter ablation was actually carried out in 81 patients (84%) who had been assigned to it and in 16 (16%) of those in the control group, the report states.

A total of 8 in the ablation group and 29 in the control arm died, received an LVAD, or went to urgent transplantation, for a hazard ratio of 0.24 (95% confidence interval, 0.11-0.52; P < .001) for the primary endpoint.

Death from any cause apparently played a big role in the risk reduction; its HR was 0.29 (95% CI, 0.12-0.72).

One peculiarity of the data, Dr. Mehra said, is that event curves for the primary endpoint and its individual components “diverge almost from day 1.” That would mean the ablation group right away started having fewer deaths, LVAD placements, or heart transplants than the control group.

“It is surprising to see such a large effect size on endpoints that are very much dependent on operators and diverge within the first day.” Probably, Dr. Mehra said, “it has to do with this being a single-center study that may not be generalizable to other practices.”

CASTLE HTx was supported by a grant from Else Kröner-Fresenius-Stiftung. Dr. Sommer discloses consulting for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr. Sohns reported no relevant financial relationships. Dr. Gustafsson discloses receiving honoraria or fees for consulting from Abbott, Alnylam Amgen, Boehringer Ingelheim, Ionis, Novartis, and Pfizer; serving on a speakers bureau for Astra Zeneca and Orion; and receiving grants from Corvia Research. Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board for NuPulseCV, Leviticus, and FineHeart.

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

Catheter ablation had long taken atrial fibrillation (AF) rhythm control to the next level before clinical trials showed it could help keep AF patients with heart failure (HF) alive and out of the hospital.

But those trials didn’t include many patients with AF on top of advanced or even end-stage HF. Lacking much of an evidence base and often viewed as too sick to gain a lot from the procedure, patients with AF and advanced HF aren’t offered ablation very often.

Now a randomized trial suggests that, on the contrary, AF ablation may confer a similar benefit to patients with HF so advanced that they were referred for evaluation at a transplant center.

The study, modestly sized with fewer than 200 such patients and conducted at a single center, assigned half of them to receive ablation and the other half to continued medical management.

Risk for the composite primary endpoint plunged 76% over a median of 18 months for those who underwent ablation. The outcome comprised death from any cause, implantation of a left ventricular assist device (LVAD), or urgent heart transplantation.

The advantage for ablation emerged early enough that the trial, CASTLE-HTx, was halted for benefit only a year after reaching its planned enrollment, observed Christian Sohns, MD, when formally presenting the results in Amsterdam at the annual congress of the European Society of Cardiology.

The difference in the primary endpoint “in this severely sick cohort of advanced, end-stage heart failure patients,” he said, was driven mostly by fewer deaths, especially cardiovascular deaths, in the ablation group.

Ablation’s effect on outcomes was associated, perhaps causally, with significant gains in left ventricular (LV) function and more than triple the reduction in AF burden seen in the control group, noted Dr. Sohns, from the Heart and Diabetes Center North-Rhine Westphalia, Bad Oeynhausen, Germany.

“Our trial suggests that in patients with atrial fibrillation and end-stage heart failure, catheter ablation may ameliorate the clinical course,” states the CASTLE-HTx primary report, published in the New England Journal of Medicine, with Dr. Sohns as lead author, in tandem with his ESC presentation.

One of the study’s key messages “is that AF ablation is safe and effective in patients with end-stage heart failure” and “should be part of our armamentarium” for treating them, said Philipp Sommer, MD, also with Heart and Diabetes Center North-Rhine Westphalia, at a press conference preceding Dr. Sohns’ presentation of CASTLE-HTx.

The intervention could potentially help such patients survive longer on transplant wait lists and even delay need for the surgery, proposed Dr. Sommer, who is senior author on the trial’s publication.

CASTLE-HTx suggests that patients with advanced HF and even persistent AF, “if they have reasonably small atria, should be actually considered for ablation, as it may prevent the need for heart transplant or LVAD implant,” said invited discussant Finn Gustafsson, MD, PhD, DMSc, after Dr. Sohns’ presentation. “And that, of course, would be a huge achievement.”

The trial “should, if anything, help eradicate the current somewhat nihilistic approach to atrial fibrillation management in patients with advanced heart failure,” said Dr. Gustafsson, medical director of cardiac transplantation and mechanical circulatory support, Rigshopsitalet Copenhagen University Hospital.

Still, he disputed the characterization by the investigators and indeed the published report that the patients, or most of them, had “end-stage heart failure.”

For example, about a third of the trial’s patients started out in NYHA class 2, Dr. Gustafsson noted. Not that they weren’t “high-risk” or their HF wasn’t severe, he offered, but they don’t seem to have been “a truly advanced heart failure population.”

The trial population consisted of “patients referred to an advanced heart failure center, rather than patients with advanced heart failure,” agreed Mandeep R. Mehra, MD, director of the Center for Advanced Heart Disease at Brigham and Woman’s Hospital, Boston.

Also citing a large prevalence of patients in NYHA class-2, Dr. Mehra added that “we almost never see paroxysmal atrial fib in these patients. It’s usually an early-stage phenomenon.” In advanced HF, AF “is usually permanent,” he told this news organization. Yet it was paroxysmal in about 30% of cases.

To its credit, Dr. Mehra observed, the study does assert that advanced HF is no reason, necessarily, to avoid catheter ablation. Nor should an AF patient’s referral to an advanced-HF center “mean that you should rush to an LVAD or transplant” before considering ablation.

The study seems to be saying, “please exhaust all options before you biologically replace the heart or put in an LVAD,” Dr. Mehra said. “Certainly, this paper steers you in that direction.”

The trial entered 194 patients with symptomatic AF and HF of at least NYHA class 2, with impaired functional capacity by the 6-minute walk test, who had been referred to a major center in Germany for a heart-transplantation workup. With all on guideline-directed medical therapy, 97 were randomly assigned open-label to catheter ablation and 97 to continued standard care.

Catheter ablation was actually carried out in 81 patients (84%) who had been assigned to it and in 16 (16%) of those in the control group, the report states.

A total of 8 in the ablation group and 29 in the control arm died, received an LVAD, or went to urgent transplantation, for a hazard ratio of 0.24 (95% confidence interval, 0.11-0.52; P < .001) for the primary endpoint.

Death from any cause apparently played a big role in the risk reduction; its HR was 0.29 (95% CI, 0.12-0.72).

One peculiarity of the data, Dr. Mehra said, is that event curves for the primary endpoint and its individual components “diverge almost from day 1.” That would mean the ablation group right away started having fewer deaths, LVAD placements, or heart transplants than the control group.

“It is surprising to see such a large effect size on endpoints that are very much dependent on operators and diverge within the first day.” Probably, Dr. Mehra said, “it has to do with this being a single-center study that may not be generalizable to other practices.”

CASTLE HTx was supported by a grant from Else Kröner-Fresenius-Stiftung. Dr. Sommer discloses consulting for Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr. Sohns reported no relevant financial relationships. Dr. Gustafsson discloses receiving honoraria or fees for consulting from Abbott, Alnylam Amgen, Boehringer Ingelheim, Ionis, Novartis, and Pfizer; serving on a speakers bureau for Astra Zeneca and Orion; and receiving grants from Corvia Research. Dr. Mehra has reported receiving payments to his institution from Abbott for consulting; consulting fees from Janssen, Mesoblast, Broadview Ventures, Natera, Paragonix, Moderna, and the Baim Institute for Clinical Research; and serving on a scientific advisory board for NuPulseCV, Leviticus, and FineHeart.

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

Patients taking long-term, low-dose glucocorticoids for rheumatoid arthritis over 2 years had a very modest relative weight gain but no relative increase in blood pressure when compared with patients who did not take the drugs, according to findings from a combined study of randomized, controlled trials (RCTs).

“This pooled analysis of five RCTs in RA found that 2 years of low-dose glucocorticoid treatment [at 7.5 mg/day or less] leads to a modest weight gain of about 1 kg but has no effect on blood pressure,” lead study author Andriko Palmowski, MD, a physician and researcher in rheumatology and clinical immunology at Charité-Universitätsmedizin Berlin, and colleagues wrote in the study, published in Annals of Internal Medicine.

“Many clinicians fear using even low-dose glucocorticoids because of the adverse effects associated with their long-term use at higher doses,” noted Leslie J. Crofford, MD, professor of medicine, pathology, microbiology, and immunology, and director of the division of rheumatology and immunology at Vanderbilt University, Nashville, Tenn.

“Indeed, long-term use of even these low doses increases risk for many significant adverse effects, including osteoporosis and cataracts in observational cohorts,” added Dr. Crofford, who was not involved in the study.

Studies were combined for stronger results

Observational studies are prone to confounding, and the RCTs in the literature have been small, resulting in low statistical power, the authors explained.

To overcome these limitations, Dr. Palmowski and associates combined individual participant data from five RCTs of glucocorticoid treatment for RA in 12 countries in Europe. The 1,112 participants had early and established RA, averaged 61.4 years of age, and 68% were women. The GLORIA trial, an RCT that contributed about 40% of the overall study population, “explicitly included elderly patients and patients with multimorbidity who are often excluded from RA trials,” the authors wrote.

Participants in the intervention group took low-dose glucocorticoids (prednisone equivalent, ≤ 7.5 mg/day; three trials used a dose of 5 mg prednisone equivalent per day); and patients in the control groups took placebo, disease-modifying antirheumatic drugs, or both. The researchers compared change over 2 years in body weight and mean arterial pressure between the groups.

At 2 years, both groups gained weight, but participants who took glucocorticoids gained an average of 1.1 kg (P < .001) more than the controls. Mean arterial pressure increased by around 2 mm Hg in both groups, with a –0.4 mm Hg between-group difference (P = .187).

Daniel G. Arkfeld MD, DDS, professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, found this “a fascinating analysis” and called the lack of change in blood pressure important.

“Steroids are used less in RA due to perceived side effects. Yet many patients have ongoing synovitis and need steroids to enable them to work and perform other activities,” said Dr. Arkfeld, who also was not involved in the study. “NSAIDs are more of an issue, with up to 10% raising blood pressure. Should we be using more steroids and less NSAIDs?”

Dr. Arkfeld also was concerned that the small 2-year weight gain may become significant over time.

Kim Marie Huffman, MD, PhD, associate professor of medicine at Duke University, Durham, N.C., agreed.

“More investigations and longer (or shorter) time periods may have yielded additional findings,” said Dr. Huffman, who also was not involved in the study. “Efforts should be made to minimize long-term prednisone use to minimize impact on weight gain and resulting consequences.”
 

Are these results applicable to U.S. patients?

“Low-dose prednisone is commonly used in the U.S.,” Dr. Huffman said. “Extrapolating the results to a U.S. population is probably fine.”

Dr. Arkfeld agreed that the results can be used to treat U.S. patients because of the large number of study participants.

According to Rebecca B. Blank, MD, PhD, rheumatologist and instructor of medicine at NYU Langone Health, New York, this is an important study. But she cautioned that the literature does not contain good data for other potential harmful effects of long-term, low-dose glucocorticoid use. “Therefore, as per both ACR [American College of Rheumatology] and EULAR [European Alliance of Associations for Rheumatology] recommendations, we should still try to limit glucocorticoids to the lowest dose and shortest duration possible in our RA patients,” advised Dr. Blank, who was not an author in the study.
 

Strengths, weaknesses, and thoughts on further research

“Pooling trials can be tricky, but these investigators used individual-level data, which increases the rigor of the analyses,” Dr. Crofford noted. “There were differences in patient populations and with the glucocorticoid doses and routes of administration. The fact that the patients in each of the studies were randomized is very important in determining if the outcomes can be attributed to the drugs or could be the results of other exposures.”

Dr. Arkfeld would like to know whether early versus late RA patients may have different results because they may have different pathophysiologies.

Dr. Huffman is interested in low-dose glucocorticoids’ impacts on glucose homeostasis, bone density, infection, and other common adverse effects.

In an accompanying editorial, David Fernandez, MD, PhD, of Hospital for Special Surgery, New York, wrote: “These findings provide a more quantifiable assessment of the potential adverse effects of steroid therapy than had existed previously and will be helpful to providers and patients as they decide on the relative risks and benefits of glucocorticoids as part of their therapy plan in rheumatoid arthritis.”

The study received no specific funding. Four of the study’s 13 authors reported financial relationships with pharmaceutical companies. Dr. Fernandez and all outside experts who commented on the study reported no relevant financial relationships.

Patients taking long-term, low-dose glucocorticoids for rheumatoid arthritis over 2 years had a very modest relative weight gain but no relative increase in blood pressure when compared with patients who did not take the drugs, according to findings from a combined study of randomized, controlled trials (RCTs).

“This pooled analysis of five RCTs in RA found that 2 years of low-dose glucocorticoid treatment [at 7.5 mg/day or less] leads to a modest weight gain of about 1 kg but has no effect on blood pressure,” lead study author Andriko Palmowski, MD, a physician and researcher in rheumatology and clinical immunology at Charité-Universitätsmedizin Berlin, and colleagues wrote in the study, published in Annals of Internal Medicine.

“Many clinicians fear using even low-dose glucocorticoids because of the adverse effects associated with their long-term use at higher doses,” noted Leslie J. Crofford, MD, professor of medicine, pathology, microbiology, and immunology, and director of the division of rheumatology and immunology at Vanderbilt University, Nashville, Tenn.

“Indeed, long-term use of even these low doses increases risk for many significant adverse effects, including osteoporosis and cataracts in observational cohorts,” added Dr. Crofford, who was not involved in the study.

Studies were combined for stronger results

Observational studies are prone to confounding, and the RCTs in the literature have been small, resulting in low statistical power, the authors explained.

To overcome these limitations, Dr. Palmowski and associates combined individual participant data from five RCTs of glucocorticoid treatment for RA in 12 countries in Europe. The 1,112 participants had early and established RA, averaged 61.4 years of age, and 68% were women. The GLORIA trial, an RCT that contributed about 40% of the overall study population, “explicitly included elderly patients and patients with multimorbidity who are often excluded from RA trials,” the authors wrote.

Participants in the intervention group took low-dose glucocorticoids (prednisone equivalent, ≤ 7.5 mg/day; three trials used a dose of 5 mg prednisone equivalent per day); and patients in the control groups took placebo, disease-modifying antirheumatic drugs, or both. The researchers compared change over 2 years in body weight and mean arterial pressure between the groups.

At 2 years, both groups gained weight, but participants who took glucocorticoids gained an average of 1.1 kg (P < .001) more than the controls. Mean arterial pressure increased by around 2 mm Hg in both groups, with a –0.4 mm Hg between-group difference (P = .187).

Daniel G. Arkfeld MD, DDS, professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, found this “a fascinating analysis” and called the lack of change in blood pressure important.

“Steroids are used less in RA due to perceived side effects. Yet many patients have ongoing synovitis and need steroids to enable them to work and perform other activities,” said Dr. Arkfeld, who also was not involved in the study. “NSAIDs are more of an issue, with up to 10% raising blood pressure. Should we be using more steroids and less NSAIDs?”

Dr. Arkfeld also was concerned that the small 2-year weight gain may become significant over time.

Kim Marie Huffman, MD, PhD, associate professor of medicine at Duke University, Durham, N.C., agreed.

“More investigations and longer (or shorter) time periods may have yielded additional findings,” said Dr. Huffman, who also was not involved in the study. “Efforts should be made to minimize long-term prednisone use to minimize impact on weight gain and resulting consequences.”
 

Are these results applicable to U.S. patients?

“Low-dose prednisone is commonly used in the U.S.,” Dr. Huffman said. “Extrapolating the results to a U.S. population is probably fine.”

Dr. Arkfeld agreed that the results can be used to treat U.S. patients because of the large number of study participants.

According to Rebecca B. Blank, MD, PhD, rheumatologist and instructor of medicine at NYU Langone Health, New York, this is an important study. But she cautioned that the literature does not contain good data for other potential harmful effects of long-term, low-dose glucocorticoid use. “Therefore, as per both ACR [American College of Rheumatology] and EULAR [European Alliance of Associations for Rheumatology] recommendations, we should still try to limit glucocorticoids to the lowest dose and shortest duration possible in our RA patients,” advised Dr. Blank, who was not an author in the study.
 

Strengths, weaknesses, and thoughts on further research

“Pooling trials can be tricky, but these investigators used individual-level data, which increases the rigor of the analyses,” Dr. Crofford noted. “There were differences in patient populations and with the glucocorticoid doses and routes of administration. The fact that the patients in each of the studies were randomized is very important in determining if the outcomes can be attributed to the drugs or could be the results of other exposures.”

Dr. Arkfeld would like to know whether early versus late RA patients may have different results because they may have different pathophysiologies.

Dr. Huffman is interested in low-dose glucocorticoids’ impacts on glucose homeostasis, bone density, infection, and other common adverse effects.

In an accompanying editorial, David Fernandez, MD, PhD, of Hospital for Special Surgery, New York, wrote: “These findings provide a more quantifiable assessment of the potential adverse effects of steroid therapy than had existed previously and will be helpful to providers and patients as they decide on the relative risks and benefits of glucocorticoids as part of their therapy plan in rheumatoid arthritis.”

The study received no specific funding. Four of the study’s 13 authors reported financial relationships with pharmaceutical companies. Dr. Fernandez and all outside experts who commented on the study reported no relevant financial relationships.

Patients taking long-term, low-dose glucocorticoids for rheumatoid arthritis over 2 years had a very modest relative weight gain but no relative increase in blood pressure when compared with patients who did not take the drugs, according to findings from a combined study of randomized, controlled trials (RCTs).

“This pooled analysis of five RCTs in RA found that 2 years of low-dose glucocorticoid treatment [at 7.5 mg/day or less] leads to a modest weight gain of about 1 kg but has no effect on blood pressure,” lead study author Andriko Palmowski, MD, a physician and researcher in rheumatology and clinical immunology at Charité-Universitätsmedizin Berlin, and colleagues wrote in the study, published in Annals of Internal Medicine.

“Many clinicians fear using even low-dose glucocorticoids because of the adverse effects associated with their long-term use at higher doses,” noted Leslie J. Crofford, MD, professor of medicine, pathology, microbiology, and immunology, and director of the division of rheumatology and immunology at Vanderbilt University, Nashville, Tenn.

“Indeed, long-term use of even these low doses increases risk for many significant adverse effects, including osteoporosis and cataracts in observational cohorts,” added Dr. Crofford, who was not involved in the study.

Studies were combined for stronger results

Observational studies are prone to confounding, and the RCTs in the literature have been small, resulting in low statistical power, the authors explained.

To overcome these limitations, Dr. Palmowski and associates combined individual participant data from five RCTs of glucocorticoid treatment for RA in 12 countries in Europe. The 1,112 participants had early and established RA, averaged 61.4 years of age, and 68% were women. The GLORIA trial, an RCT that contributed about 40% of the overall study population, “explicitly included elderly patients and patients with multimorbidity who are often excluded from RA trials,” the authors wrote.

Participants in the intervention group took low-dose glucocorticoids (prednisone equivalent, ≤ 7.5 mg/day; three trials used a dose of 5 mg prednisone equivalent per day); and patients in the control groups took placebo, disease-modifying antirheumatic drugs, or both. The researchers compared change over 2 years in body weight and mean arterial pressure between the groups.

At 2 years, both groups gained weight, but participants who took glucocorticoids gained an average of 1.1 kg (P < .001) more than the controls. Mean arterial pressure increased by around 2 mm Hg in both groups, with a –0.4 mm Hg between-group difference (P = .187).

Daniel G. Arkfeld MD, DDS, professor of clinical medicine in the division of rheumatology at the University of Southern California, Los Angeles, found this “a fascinating analysis” and called the lack of change in blood pressure important.

“Steroids are used less in RA due to perceived side effects. Yet many patients have ongoing synovitis and need steroids to enable them to work and perform other activities,” said Dr. Arkfeld, who also was not involved in the study. “NSAIDs are more of an issue, with up to 10% raising blood pressure. Should we be using more steroids and less NSAIDs?”

Dr. Arkfeld also was concerned that the small 2-year weight gain may become significant over time.

Kim Marie Huffman, MD, PhD, associate professor of medicine at Duke University, Durham, N.C., agreed.

“More investigations and longer (or shorter) time periods may have yielded additional findings,” said Dr. Huffman, who also was not involved in the study. “Efforts should be made to minimize long-term prednisone use to minimize impact on weight gain and resulting consequences.”
 

Are these results applicable to U.S. patients?

“Low-dose prednisone is commonly used in the U.S.,” Dr. Huffman said. “Extrapolating the results to a U.S. population is probably fine.”

Dr. Arkfeld agreed that the results can be used to treat U.S. patients because of the large number of study participants.

According to Rebecca B. Blank, MD, PhD, rheumatologist and instructor of medicine at NYU Langone Health, New York, this is an important study. But she cautioned that the literature does not contain good data for other potential harmful effects of long-term, low-dose glucocorticoid use. “Therefore, as per both ACR [American College of Rheumatology] and EULAR [European Alliance of Associations for Rheumatology] recommendations, we should still try to limit glucocorticoids to the lowest dose and shortest duration possible in our RA patients,” advised Dr. Blank, who was not an author in the study.
 

Strengths, weaknesses, and thoughts on further research

“Pooling trials can be tricky, but these investigators used individual-level data, which increases the rigor of the analyses,” Dr. Crofford noted. “There were differences in patient populations and with the glucocorticoid doses and routes of administration. The fact that the patients in each of the studies were randomized is very important in determining if the outcomes can be attributed to the drugs or could be the results of other exposures.”

Dr. Arkfeld would like to know whether early versus late RA patients may have different results because they may have different pathophysiologies.

Dr. Huffman is interested in low-dose glucocorticoids’ impacts on glucose homeostasis, bone density, infection, and other common adverse effects.

In an accompanying editorial, David Fernandez, MD, PhD, of Hospital for Special Surgery, New York, wrote: “These findings provide a more quantifiable assessment of the potential adverse effects of steroid therapy than had existed previously and will be helpful to providers and patients as they decide on the relative risks and benefits of glucocorticoids as part of their therapy plan in rheumatoid arthritis.”

The study received no specific funding. Four of the study’s 13 authors reported financial relationships with pharmaceutical companies. Dr. Fernandez and all outside experts who commented on the study reported no relevant financial relationships.

AMSTERDAM – The more weight patients lost while on weekly semaglutide treatment in the STEP-HFpEF trial, the better their outcomes, suggesting that weight loss by itself was a major reason why the treatment improved a broad range of prespecified study outcomes, including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.

At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.

Mitchel L. Zoler/MDedge News

His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.

The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.

Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.

In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m²), class 2 (35-39 kg/m²), and class 3 (≥ 40 kg/m²) obesity.

Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
 

Not every benefit was fully mediated by weight loss

These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”

He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.

“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.

“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.

Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.

“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.

Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.

“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.

STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
 

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

AMSTERDAM – The more weight patients lost while on weekly semaglutide treatment in the STEP-HFpEF trial, the better their outcomes, suggesting that weight loss by itself was a major reason why the treatment improved a broad range of prespecified study outcomes, including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.

At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.

Mitchel L. Zoler/MDedge News

His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.

The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.

Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.

In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m²), class 2 (35-39 kg/m²), and class 3 (≥ 40 kg/m²) obesity.

Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
 

Not every benefit was fully mediated by weight loss

These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”

He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.

“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.

“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.

Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.

“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.

Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.

“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.

STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
 

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

AMSTERDAM – The more weight patients lost while on weekly semaglutide treatment in the STEP-HFpEF trial, the better their outcomes, suggesting that weight loss by itself was a major reason why the treatment improved a broad range of prespecified study outcomes, including symptoms and physical limitations, exercise capacity, and inflammation, new analyses from the trial show.

At the annual congress of the European Society of Cardiology where he presented these new findings, Mikhail N. Kosiborod, MD, also posited that weight loss produced by weekly subcutaneous injections of 2.4 mg semaglutide (Wegovy) for 52 weeks in the study does not fully explain the multiple mechanisms that may be involved in producing this intervention’s effects in the STEP-HFpEF trial.

Mitchel L. Zoler/MDedge News

His report earlier at the congress and in a simultaneously published report of the trial’s primary outcomes established a role for medically induced weight loss in managing patients with obesity-phenotype HFpEF in a total of 529 randomized individuals with HFpEF and obesity but without diabetes.

The new analyses showed that for one of the two primary endpoints – the change from baseline in patients’ assessment on the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ), the placebo-adjusted average change was a 16.1-point improvement in the 51 people with a 5%-10% weight loss during the 1-year study, and a 21.6-point improvement in the 58 who had at least a 20% weight loss, a between-group average 5.5 point difference that represents a clinically meaningful incremental improvement in this validated metric of symptoms and functional limitations.

Similar weight-related differences in benefit also occurred for the secondary outcomes of changes from baseline in 6-minute walk distance and in levels of C-reactive protein (CRP), a measure of systemic inflammation.

In an adjusted regression model, every 10% drop from baseline body weight was significantly linked with a 6.4-point improvement in KCCQ score, a 14.4 meter improvement in 6-minute walk distance, and a 28% relative reduction from baseline in CRP, reported Dr. Kosiborod, a cardiologist and codirector of the Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute in Kansas City, Mo.

These new, prespecified analyses also showed that people with obesity and HFpEF responded roughly the same to semaglutide treatment compared with placebo-treated controls regardless of their starting body mass index, including people with class 1 (30-34 kg/m²), class 2 (35-39 kg/m²), and class 3 (≥ 40 kg/m²) obesity.

Simultaneously with Dr. Kosiborod’s report at the congress, these findings appeared in a report posted online in Nature Medicine.
 

Not every benefit was fully mediated by weight loss

These analyses “do not tell us how much of the benefit was mediated by weight loss, but the data do say that the more weight a person lost, the more benefit they got,” Dr. Kosiborod explained in an interview. “That is not the same as saying that everything is mediated by weight. It doesn’t say that nothing beyond weight loss matters.”

He and his associates are planning a mediation analysis of data from STEP-HFpEF that will more directly address this issue.

“It’s likely that people who lost more weight with semaglutide also had greater benefits from other effects of semaglutide at the same time. Weight loss is a good surrogate marker” for the range of effects that a person receives from treatment with semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, Dr. Kosiborod said.

“GLP-1 receptor agonists may have direct effects on atherosclerosis, as well as other effects that are uncoupled from weight loss,” such as proven anti-inflammatory effects, he added.

Another exploratory effect from semaglutide treatment in the study and reported by Dr. Kosiborod was a significant reduction in serum levels of N-terminal pro brain natriuretic peptide, an association never previously seen with weight loss in people with heart failure.

“The outcomes we’ve already seen in STEP-HFpEF were largely symptomatic, which are extraordinarily important, but there may be a completely different relationship between weight and clinical events,” said John E. Deanfield, PhD, a professor of cardiology at University College Hospital, London, who was not involved in the study.

Dr. Deanfield noted that important prognostic markers such as cholesterol levels and blood pressure reductions are usually not temporally related to weight loss. “The idea that [the benefits seen in STEP-HFpEF] are purely from weight loss is something we need to be careful about,” he said.

“My gut feeling is that at least 75% of the effect [in STEP-HFpEF} was due to weight loss,” said Naveed Sattar, PhD, professor of metabolic medicine at the University of Glasgow, who was not associated with the research.

STEP-HFpEF was funded by Novo Nordisk, the company that markets semaglutide (Wegovy). Dr. Kosiborod has been a consultant and adviser to, and has received honoraria from, Novo Nordisk. He has been a consultant to numerous other companies, received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer, honoraria from AstraZeneca, and is a stockholder in Artera Health and Saghmos Therapeutics. Dr. Deanfield has been a consultant to Novo Nordisk as well as to Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Sanofi, and Takeda, and has received research funding from Aegerion, Colgate, MSD, Pfizer, and Roche. Dr. Sattar has been a consultant to Novo Nordisk as well as to Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche Diagnostics.
 

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

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

TOPLINE:

Both short and long sleep durations appear to increase the risk for type 2 diabetes, independent of lifestyle and cardiovascular risk factors, suggests an analysis of a Dutch study.

METHODOLOGY:

• Data on 5,561 participants aged 40–75 years from The Maastricht Study who completed the baseline survey between November 2010 and January 2018 and had full data available were included.
• Sleep duration was assessed as the in-bed time in minutes, using a median of 7 nights’ data from an activPAL3 (PAL Technologies) accelerometer, which is worn on the thigh.
• Glucose metabolism was determined via an oral glucose tolerance test and categorized as prediabetes or type 2 diabetes in line with World Health Organization diagnostic criteria.
• The association between sleep duration and type 2 diabetes was assessed on multivariate logistic regression analysis, taking into account a range of potential confounding factors.

TAKEAWAY:

• The mean age of the participants was 60.1 years, and there was an even split between men and women. In all, 832 had prediabetes and 1,341 type 2 diabetes, and the mean sleep duration was 8.3 hours.
• The results indicated there was a U-shaped relationship between sleep duration and type 2 diabetes, so that both long and short sleep durations increased the risk.
• In the fully adjusted model, a sleep duration of 5 hours was associated with an odds ratio for type 2 diabetes versus 8 hours sleep of 2.9. For a sleep duration of 12 hours, the odds ratio was 1.8.
• The association between sleep duration and diabetes was not significant.

IN PRACTICE:

The results “support the idea that sleep duration could be a relevant risk factor for type 2 diabetes independent of lifestyle risk factors, including diet, physical activity, smoking behavior, and alcohol consumption,” wrote the authors.

“These findings underpin the importance of promoting healthy sleep habits to avoid sleep deprivation,” they added.
 

STUDY DETAILS:

The research was led by Jeroen D. Albers, MSc, department of social medicine, Maastricht (the Netherlands) University, and published in Sleep Health. It is an analysis of The Maastricht Study.

LIMITATIONS:

The study is limited by its cross-sectional nature, particularly because there are “plausible causal paths between sleep duration and type 2 in both directions,” the authors note. The accelerometer used in the study also cannot reliably distinguish between waking and sleeping time in bed, with the potential for misclassification. Daytime naps were also not included, and long-term changes sleep patterns were not measured. In addition, it was not possible to control for some potential confounding factors.

DISCLOSURES:

The Maastricht Study was supported by the European Regional Development Fund via OP-Zuid, the Province of Limburg, the Dutch Ministry of Economic Affairs, Stichting De Weijerhorst, the Pearl String Initiative Diabetes, the School for Cardiovascular Diseases, the School for Public Health and Primary Care, the School for Nutrition and Translational Research in Metabolism, Stichting Annadal, Health Foundation Limburg, and unrestricted grants from Janssen-Cilag, Novo Nordisk, and Sanofi Aventis Netherlands. One author declares a relationship with Novo Nordisk outside the submitted work. No other relevant financial relationships were declared.

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

Severe COVID infections may lead to lasting damage to the immune system, new research finds.

The small study, published in Cell and funded by the National Institutes of Health, details how immune cells were analyzed through blood samples collected from 38 patients recovering from severe COVID and other critical illnesses, and from 19 healthy people. Researchers from Weill Cornell Medicine, New York, and The Jackson Laboratory for Genomic Medicine, Farmington, Conn., found through isolating hematopoietic stem cells that people recovering from severe bouts of COVID had changes to their DNA that were passed down to offspring cells.

The research team, led by Steven Josefowicz, PhD, of Weill Cornell’s pathology department, and Duygu Ucar, PhD, associate professor at The Jackson Laboratory for Genomic Medicine, discovered that this chain reaction of stem cell changes caused a boost in the production of monocytes. The authors found that, due to the innate cellular changes from a severe case of COVID, patients in recovery ended up producing a larger amount of inflammatory cytokines, rather than monocytes – distinct from samples collected from healthy patients and those recovering from other critical illnesses.

These changes to patients’ epigenetic landscapes were observed even a year after the initial COVID-19 infection. While the small participant pool meant that the research team could not establish a direct line between these innate changes and any ensuing health outcomes, the research provides us with clues as to why patients continue to struggle with inflammation and long COVID symptoms well after they recover.

While the authors reiterate the study’s limitations and hesitate to make any clear-cut associations between the results and long-term health outcomes, Wolfgang Leitner, PhD, from the NIH’s National Institute of Allergy and Infectious Diseases, predicts that long COVID can, at least in part, be explained by the changes in innate immune responses.

“Ideally, the authors would have had cells from each patient before they got infected, as a comparator, to see what the epigenetic landscape was before COVID changed it,” said Dr. Leitner. “Clear links between the severity of COVID and genetics were discovered already early in the pandemic and this paper should prompt follow-up studies that link mutations in immune genes with the epigenetic changes described here.”

Dr. Leitner said he had some initial predictions about the long-term impact of COVID-19, but he had not anticipated some of what the study’s findings now show.

“Unlike in the case of, for example, influenza, where the lungs go into ‘repair mode’ after the infection has been resolved – which leaves people susceptible to secondary infections for up to several months – this study shows that after severe COVID, the immune system remains in ‘emergency mode’ and in a heightened state of inflammation,” said Dr. Leitner.

“That further aggravates the problem the initial strong inflammation causes: even higher risk of autoimmune disease, but also, cancer.”

Commenting on the findings, Eric Topol, MD, editor-in-chief of Medscape Medical News, said the study presents “evidence that a key line of immune cells are essentially irrevocably, epigenetically altered and activated.

“You do not want to have this [COVID],” he added.

The study also highlights the researchers’ novel approach to isolating hematopoietic stem cells, found largely in bone marrow. This type of research has been limited in the past because of how costly and invasive it can be to analyze cells in bone marrow. But, by isolating and enriching hematopoietic stem cells, the team can decipher the full cellular diversity of the cells’ bone marrow counterparts.

“This revelation opened the doors to study, at single-cell resolution, how stem cells are affected upon infection and vaccination with a simple blood draw,” representatives from the Jackson lab said in a press release.

A version of this article appeared on Medscape.com.

Severe COVID infections may lead to lasting damage to the immune system, new research finds.

The small study, published in Cell and funded by the National Institutes of Health, details how immune cells were analyzed through blood samples collected from 38 patients recovering from severe COVID and other critical illnesses, and from 19 healthy people. Researchers from Weill Cornell Medicine, New York, and The Jackson Laboratory for Genomic Medicine, Farmington, Conn., found through isolating hematopoietic stem cells that people recovering from severe bouts of COVID had changes to their DNA that were passed down to offspring cells.

The research team, led by Steven Josefowicz, PhD, of Weill Cornell’s pathology department, and Duygu Ucar, PhD, associate professor at The Jackson Laboratory for Genomic Medicine, discovered that this chain reaction of stem cell changes caused a boost in the production of monocytes. The authors found that, due to the innate cellular changes from a severe case of COVID, patients in recovery ended up producing a larger amount of inflammatory cytokines, rather than monocytes – distinct from samples collected from healthy patients and those recovering from other critical illnesses.

These changes to patients’ epigenetic landscapes were observed even a year after the initial COVID-19 infection. While the small participant pool meant that the research team could not establish a direct line between these innate changes and any ensuing health outcomes, the research provides us with clues as to why patients continue to struggle with inflammation and long COVID symptoms well after they recover.

While the authors reiterate the study’s limitations and hesitate to make any clear-cut associations between the results and long-term health outcomes, Wolfgang Leitner, PhD, from the NIH’s National Institute of Allergy and Infectious Diseases, predicts that long COVID can, at least in part, be explained by the changes in innate immune responses.

“Ideally, the authors would have had cells from each patient before they got infected, as a comparator, to see what the epigenetic landscape was before COVID changed it,” said Dr. Leitner. “Clear links between the severity of COVID and genetics were discovered already early in the pandemic and this paper should prompt follow-up studies that link mutations in immune genes with the epigenetic changes described here.”

Dr. Leitner said he had some initial predictions about the long-term impact of COVID-19, but he had not anticipated some of what the study’s findings now show.

“Unlike in the case of, for example, influenza, where the lungs go into ‘repair mode’ after the infection has been resolved – which leaves people susceptible to secondary infections for up to several months – this study shows that after severe COVID, the immune system remains in ‘emergency mode’ and in a heightened state of inflammation,” said Dr. Leitner.

“That further aggravates the problem the initial strong inflammation causes: even higher risk of autoimmune disease, but also, cancer.”

Commenting on the findings, Eric Topol, MD, editor-in-chief of Medscape Medical News, said the study presents “evidence that a key line of immune cells are essentially irrevocably, epigenetically altered and activated.

“You do not want to have this [COVID],” he added.

The study also highlights the researchers’ novel approach to isolating hematopoietic stem cells, found largely in bone marrow. This type of research has been limited in the past because of how costly and invasive it can be to analyze cells in bone marrow. But, by isolating and enriching hematopoietic stem cells, the team can decipher the full cellular diversity of the cells’ bone marrow counterparts.

“This revelation opened the doors to study, at single-cell resolution, how stem cells are affected upon infection and vaccination with a simple blood draw,” representatives from the Jackson lab said in a press release.

A version of this article appeared on Medscape.com.

Severe COVID infections may lead to lasting damage to the immune system, new research finds.

The small study, published in Cell and funded by the National Institutes of Health, details how immune cells were analyzed through blood samples collected from 38 patients recovering from severe COVID and other critical illnesses, and from 19 healthy people. Researchers from Weill Cornell Medicine, New York, and The Jackson Laboratory for Genomic Medicine, Farmington, Conn., found through isolating hematopoietic stem cells that people recovering from severe bouts of COVID had changes to their DNA that were passed down to offspring cells.

The research team, led by Steven Josefowicz, PhD, of Weill Cornell’s pathology department, and Duygu Ucar, PhD, associate professor at The Jackson Laboratory for Genomic Medicine, discovered that this chain reaction of stem cell changes caused a boost in the production of monocytes. The authors found that, due to the innate cellular changes from a severe case of COVID, patients in recovery ended up producing a larger amount of inflammatory cytokines, rather than monocytes – distinct from samples collected from healthy patients and those recovering from other critical illnesses.

These changes to patients’ epigenetic landscapes were observed even a year after the initial COVID-19 infection. While the small participant pool meant that the research team could not establish a direct line between these innate changes and any ensuing health outcomes, the research provides us with clues as to why patients continue to struggle with inflammation and long COVID symptoms well after they recover.

While the authors reiterate the study’s limitations and hesitate to make any clear-cut associations between the results and long-term health outcomes, Wolfgang Leitner, PhD, from the NIH’s National Institute of Allergy and Infectious Diseases, predicts that long COVID can, at least in part, be explained by the changes in innate immune responses.

“Ideally, the authors would have had cells from each patient before they got infected, as a comparator, to see what the epigenetic landscape was before COVID changed it,” said Dr. Leitner. “Clear links between the severity of COVID and genetics were discovered already early in the pandemic and this paper should prompt follow-up studies that link mutations in immune genes with the epigenetic changes described here.”

Dr. Leitner said he had some initial predictions about the long-term impact of COVID-19, but he had not anticipated some of what the study’s findings now show.

“Unlike in the case of, for example, influenza, where the lungs go into ‘repair mode’ after the infection has been resolved – which leaves people susceptible to secondary infections for up to several months – this study shows that after severe COVID, the immune system remains in ‘emergency mode’ and in a heightened state of inflammation,” said Dr. Leitner.

“That further aggravates the problem the initial strong inflammation causes: even higher risk of autoimmune disease, but also, cancer.”

Commenting on the findings, Eric Topol, MD, editor-in-chief of Medscape Medical News, said the study presents “evidence that a key line of immune cells are essentially irrevocably, epigenetically altered and activated.

“You do not want to have this [COVID],” he added.

The study also highlights the researchers’ novel approach to isolating hematopoietic stem cells, found largely in bone marrow. This type of research has been limited in the past because of how costly and invasive it can be to analyze cells in bone marrow. But, by isolating and enriching hematopoietic stem cells, the team can decipher the full cellular diversity of the cells’ bone marrow counterparts.

“This revelation opened the doors to study, at single-cell resolution, how stem cells are affected upon infection and vaccination with a simple blood draw,” representatives from the Jackson lab said in a press release.

A version of this article appeared on Medscape.com.

Those who run Taylor Swift’s Eras Tour have something in common with those who run ERAS, the Electronic Residency Application Service. They cause agita to the people they purport to serve.

Most medical students won’t see Taylor Swift perform her hit song “Cruel Summer,” but they will spend thousands of dollars on ERAS as they prepare for the 2024 residency match. Medical students applying for residency tend to be as stressed out as Swifties trying to score concert tickets. Aside from the expenses of residency applications, students also face an increasingly complex application process: a match algorithm many of them do not understand and major changes to the application process that most learn about right before the application cycle begins.

I have gone through two matches myself, one for internal medicine and one for neurology, and I have also guided students through the process for almost a decade as a dean of student affairs at a medical school. Every summer, the application process is filled with numerous changes, often with little, if any, warning for the students. One year, for example, a specialty required additional essays tailored to each program. Though this requirement may have helped programs discern which students are most enthusiastic about their programs, it also disadvantaged students working on busier rotations, strapped for time to write as many as 70 additional essays in a matter of weeks.

Other recent changes have included “signaling” programs, selecting preferred regions, and preinterview recordings for some specialties. In 2023, students cannot include more than 10 activities on their ERAS application. I have spoken to students at numerous medical schools concerned about the difficulty of selecting 10 activities out of dozens of meaningful pursuits throughout their journeys; this challenge is particularly acute for students who had other careers before entering medical school.

The stress continues to mount even after residency applications have been submitted. Students often feel tied to their phones because offers for residency interviews roll in day and night by email, and if they wait more than a few hours to respond, they’re often moved to a waiting list for their preferred interview date. One year, while we were rounding on patients, a student stepped away to schedule an interview; while doing so, he missed out on managing a patient who developed a neurologic emergency. Thankfully, many but not all specialties have put rules in place to allow students more time to think through interview offers. Having more time to think, even if it’s just 48 hours, may decrease stress, limit the negative impacts on medical education, and promote informed decisions during interview season.

To be sure, most changes are being made in an effort to improve the experience of the students and programs. But as with anything, the result has been a mix of good and bad. The transition to virtual interviews allowed students to apply more broadly to programs without worrying about travel costs. The move also benefits students with disabilities who face accessibility and other challenges with traveling. However, virtual interviews came with several downsides, including but not limited to an increased number of applications submitted (recall that this was also a benefit), interview hoarding, and challenges of connecting personally via virtual platform. Despite the virtual format, applicants increasingly are doing in-person second looks, which some worry may give those applicants an additional advantage over applicants who do not have the time or financial resources to travel for a second look. Despite these shortcomings, it is important that virtual interviews remain an option for those applicants who need it.

Another change, which has been extensively debated in medical education in recent years, was the switch to pass/fail on the USMLE Step 1 exam. Though this move decreased the stress students experienced in the first 2 years of medical school, it has resulted in a new challenge as many residency programs put more emphasis on USMLE Step 2. Many medical students feel they do not have a good gauge of their competitiveness until a few weeks before they submit their application, particularly those applicants attending medical schools that do not provide them with information regarding their class standing until right before they submit their applications.

By the time Swift’s Eras Tour ends in the summer of 2024, medical students will already have matched and started their residency programs. At the same time, a new batch of students will be entering the next year’s match. Though the number of anticipated changes may not reach the level of seismic activity caused by the Swifties at her Seattle concert, many medical students fear that the changes may be just like tectonic plates shifting the match process away from its original purpose: to provide an orderly and fair mechanism for matching the preferences of applicants for U.S. residency positions with the preferences of residency program directors.

Dr. Etienne is with WMCHealth Good Samaritan Hospital, New York, and New York Medical College. He disclosed no relevant conflicts of interest.

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

Those who run Taylor Swift’s Eras Tour have something in common with those who run ERAS, the Electronic Residency Application Service. They cause agita to the people they purport to serve.

Most medical students won’t see Taylor Swift perform her hit song “Cruel Summer,” but they will spend thousands of dollars on ERAS as they prepare for the 2024 residency match. Medical students applying for residency tend to be as stressed out as Swifties trying to score concert tickets. Aside from the expenses of residency applications, students also face an increasingly complex application process: a match algorithm many of them do not understand and major changes to the application process that most learn about right before the application cycle begins.

I have gone through two matches myself, one for internal medicine and one for neurology, and I have also guided students through the process for almost a decade as a dean of student affairs at a medical school. Every summer, the application process is filled with numerous changes, often with little, if any, warning for the students. One year, for example, a specialty required additional essays tailored to each program. Though this requirement may have helped programs discern which students are most enthusiastic about their programs, it also disadvantaged students working on busier rotations, strapped for time to write as many as 70 additional essays in a matter of weeks.

Other recent changes have included “signaling” programs, selecting preferred regions, and preinterview recordings for some specialties. In 2023, students cannot include more than 10 activities on their ERAS application. I have spoken to students at numerous medical schools concerned about the difficulty of selecting 10 activities out of dozens of meaningful pursuits throughout their journeys; this challenge is particularly acute for students who had other careers before entering medical school.

The stress continues to mount even after residency applications have been submitted. Students often feel tied to their phones because offers for residency interviews roll in day and night by email, and if they wait more than a few hours to respond, they’re often moved to a waiting list for their preferred interview date. One year, while we were rounding on patients, a student stepped away to schedule an interview; while doing so, he missed out on managing a patient who developed a neurologic emergency. Thankfully, many but not all specialties have put rules in place to allow students more time to think through interview offers. Having more time to think, even if it’s just 48 hours, may decrease stress, limit the negative impacts on medical education, and promote informed decisions during interview season.

To be sure, most changes are being made in an effort to improve the experience of the students and programs. But as with anything, the result has been a mix of good and bad. The transition to virtual interviews allowed students to apply more broadly to programs without worrying about travel costs. The move also benefits students with disabilities who face accessibility and other challenges with traveling. However, virtual interviews came with several downsides, including but not limited to an increased number of applications submitted (recall that this was also a benefit), interview hoarding, and challenges of connecting personally via virtual platform. Despite the virtual format, applicants increasingly are doing in-person second looks, which some worry may give those applicants an additional advantage over applicants who do not have the time or financial resources to travel for a second look. Despite these shortcomings, it is important that virtual interviews remain an option for those applicants who need it.

Another change, which has been extensively debated in medical education in recent years, was the switch to pass/fail on the USMLE Step 1 exam. Though this move decreased the stress students experienced in the first 2 years of medical school, it has resulted in a new challenge as many residency programs put more emphasis on USMLE Step 2. Many medical students feel they do not have a good gauge of their competitiveness until a few weeks before they submit their application, particularly those applicants attending medical schools that do not provide them with information regarding their class standing until right before they submit their applications.

By the time Swift’s Eras Tour ends in the summer of 2024, medical students will already have matched and started their residency programs. At the same time, a new batch of students will be entering the next year’s match. Though the number of anticipated changes may not reach the level of seismic activity caused by the Swifties at her Seattle concert, many medical students fear that the changes may be just like tectonic plates shifting the match process away from its original purpose: to provide an orderly and fair mechanism for matching the preferences of applicants for U.S. residency positions with the preferences of residency program directors.

Dr. Etienne is with WMCHealth Good Samaritan Hospital, New York, and New York Medical College. He disclosed no relevant conflicts of interest.

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

Those who run Taylor Swift’s Eras Tour have something in common with those who run ERAS, the Electronic Residency Application Service. They cause agita to the people they purport to serve.

Most medical students won’t see Taylor Swift perform her hit song “Cruel Summer,” but they will spend thousands of dollars on ERAS as they prepare for the 2024 residency match. Medical students applying for residency tend to be as stressed out as Swifties trying to score concert tickets. Aside from the expenses of residency applications, students also face an increasingly complex application process: a match algorithm many of them do not understand and major changes to the application process that most learn about right before the application cycle begins.

I have gone through two matches myself, one for internal medicine and one for neurology, and I have also guided students through the process for almost a decade as a dean of student affairs at a medical school. Every summer, the application process is filled with numerous changes, often with little, if any, warning for the students. One year, for example, a specialty required additional essays tailored to each program. Though this requirement may have helped programs discern which students are most enthusiastic about their programs, it also disadvantaged students working on busier rotations, strapped for time to write as many as 70 additional essays in a matter of weeks.

Other recent changes have included “signaling” programs, selecting preferred regions, and preinterview recordings for some specialties. In 2023, students cannot include more than 10 activities on their ERAS application. I have spoken to students at numerous medical schools concerned about the difficulty of selecting 10 activities out of dozens of meaningful pursuits throughout their journeys; this challenge is particularly acute for students who had other careers before entering medical school.

The stress continues to mount even after residency applications have been submitted. Students often feel tied to their phones because offers for residency interviews roll in day and night by email, and if they wait more than a few hours to respond, they’re often moved to a waiting list for their preferred interview date. One year, while we were rounding on patients, a student stepped away to schedule an interview; while doing so, he missed out on managing a patient who developed a neurologic emergency. Thankfully, many but not all specialties have put rules in place to allow students more time to think through interview offers. Having more time to think, even if it’s just 48 hours, may decrease stress, limit the negative impacts on medical education, and promote informed decisions during interview season.

To be sure, most changes are being made in an effort to improve the experience of the students and programs. But as with anything, the result has been a mix of good and bad. The transition to virtual interviews allowed students to apply more broadly to programs without worrying about travel costs. The move also benefits students with disabilities who face accessibility and other challenges with traveling. However, virtual interviews came with several downsides, including but not limited to an increased number of applications submitted (recall that this was also a benefit), interview hoarding, and challenges of connecting personally via virtual platform. Despite the virtual format, applicants increasingly are doing in-person second looks, which some worry may give those applicants an additional advantage over applicants who do not have the time or financial resources to travel for a second look. Despite these shortcomings, it is important that virtual interviews remain an option for those applicants who need it.

Another change, which has been extensively debated in medical education in recent years, was the switch to pass/fail on the USMLE Step 1 exam. Though this move decreased the stress students experienced in the first 2 years of medical school, it has resulted in a new challenge as many residency programs put more emphasis on USMLE Step 2. Many medical students feel they do not have a good gauge of their competitiveness until a few weeks before they submit their application, particularly those applicants attending medical schools that do not provide them with information regarding their class standing until right before they submit their applications.

By the time Swift’s Eras Tour ends in the summer of 2024, medical students will already have matched and started their residency programs. At the same time, a new batch of students will be entering the next year’s match. Though the number of anticipated changes may not reach the level of seismic activity caused by the Swifties at her Seattle concert, many medical students fear that the changes may be just like tectonic plates shifting the match process away from its original purpose: to provide an orderly and fair mechanism for matching the preferences of applicants for U.S. residency positions with the preferences of residency program directors.

Dr. Etienne is with WMCHealth Good Samaritan Hospital, New York, and New York Medical College. He disclosed no relevant conflicts of interest.

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