TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

• Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
• For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
• Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

• The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
• Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
• The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

• Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
• For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
• Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

• The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
• Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
• The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

TOPLINE:

Cerebral palsy (CP) affects 1-4 per 1,000 live births in the United States. A new cohort study found children conceived during the winter and spring months appear to have a slightly higher risk for developing CP than those conceived during the summer. Fall months carried about the same or only slightly higher risk of CP than summer months.

METHODOLOGY:

• Researchers examined data from nearly 4.5 million live births registered in California between 2007 and 2015, exploring if the season of conception could serve as an indicator of exposure to environmental risk factors.
• For instance, infants conceived in winter months may have higher exposure to viruses like influenza. In California, agricultural pesticides are most often applied in summer months, when pregnant people would be in their first or second trimester and receive their most exposure to the fine particulates, the authors hypothesize.
• Almost 4,700 babies in the study population were diagnosed with CP. Researchers also considered the role of preterm birth as a potential mediating factor, and adjusted for sociodemographic characteristics such as maternal age, race, education, smoking during pregnancy, and body mass index.

TAKEAWAY:

• The study found that children conceived in winter and spring had a 9% (95% confidence interval, 1.01-1.19) to 10% (95% CI, 1.02-1.20) higher risk of developing CP than those conceived in the summer.
• Children conceived in January, February, or May carried a 15% higher risk, compared with babies conceived in July.
• The risk was more pronounced among mothers with low education levels or living in neighborhoods where residents have high rates of unemployment, single-parent households, multiunit households, and lower rates of high school graduates.

IN PRACTICE:

The researchers noted that possible explanations for the seasonal link to CP risk may include the prevalence of maternal infections during pregnancy, variations in exposure to pesticides, and seasonal patterns for air pollution. “Investigating seasonal variations in disease occurrence can provide clues about etiologically relevant factors.”

SOURCE:

Lead author Haoran Zhou, MPH, Yale University, New Haven, Conn., and colleagues published their findings online in JAMA Network Open. The study was partly supported by a grant from the American Academy for Cerebral Palsy and Developmental Medicine.

LIMITATIONS:

The study may not have fully captured all children with CP in the cohort due to the possibility of misclassification. The findings may not be generalizable beyond California. The overall increased risk associated with the season of conception was relatively small, suggesting family planning strategies may not need to change based on these findings. The exact mechanisms involving potential environmental factors need further investigation.

DISCLOSURES:

The authors reported no relevant financial relationships.

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

SAN DIEGO – The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”

In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

SAN DIEGO – The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”

In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

SAN DIEGO – The use of absorbable threads to improve skin laxity is safe and effective, but their long-term aesthetic effects remain unclear, according to Catherine M. DiGiorgio, MD, MS.

In the 1990s, clinicians used nonabsorbable sutures for thread lifts, including polypropylene-barbed threads, which caused adverse events ranging from extrusion and migration to thread expulsion, dimpling, granuloma formation, and prolonged pain, Dr. DiGiorgio, a laser and cosmetic dermatologist who practices in Boston, said at the annual Masters of Aesthetics Symposium. As a result, the Food and Drug Administration withdrew its approval of contour thread aesthetic procedures in 2009. Since then, the development of absorbable threads made from a hybrid of poly-l-lactic acid (PLLA) and polyglycolide/l-lactide (PLGA), and from polydioxanone (PDO) has led to renewed interest in thread lift procedures.

Dr. DiGiorgio

While a surgical facelift remains the gold standard, “we have some options to offer patients for noninvasive tightening,” Dr. DiGiorgio said. “We have devices that provide minimal downtime and are less costly, but results are inconsistent. Thread lifts, or suspension sutures, also have minimal downtime and are less costly, but the [results are] subtle and not long lasting.”

PLGA/PLLA threads consist of an 18% PLGA and 82% PLLA monofilament with bidirectional cones that shift the tissue. They are available in 8, 12, or 16 cones spaced 5-8 mm apart on either side of a 2-cm central cone-free area. “There is a 12-cm, 23-gauge needle on either side of the thread, to allow for insertion,” she explained. “These cones stimulate types I and II collagen, which results in collagenesis. The skin encapsulates the cones, resulting in lasting volume and contour.”

PDO threads, meanwhile, are biodegradable by hydrolysis over 4-8 months. They are inserted with a cannula or a needle and vary based on length, diameter, twined vs. braided, coned vs. barbed, and twisted vs. smooth. “The barbed PDO threads are what I use the most,” Dr. DiGiorgio said. “They provide slight tissue repositioning by anchoring and gripping.”

In 2019, researchers in Korea published results of a study that evaluated the collagen-producing effects of powdered PDO injection, compared with PLLA injection, in a murine model. They found that while both PDO and PLLA induced granulomatous reactions and collagen formation, PDO resulted in slightly more collagen formation than PLLA.

Dr. DiGiorgio, who transitioned to using PDO threads after first using the PLLA/PLGA threads, said that both are effective. “I find PDO threads to be easier. They’re less costly for me, they’re less costly for the patient, and the results are about equivalent.”

Absorbable threads are indicated for the cheek, jawline, neck, lips, forehead, and brow. She finds them most useful “for the lower face, below the nasolabial fold down to the jawline, for improvement of the jowls,” she said. “I don’t think they really work on the neck.”

As with any cosmetic procedure, patient selection is key. According to Dr. DiGiorgio, the patient should have specific and segmental areas of facial laxity amenable to lifting and recontouring along a straight-line vector, adequate dermal thickness, and appropriate expectations for the level of correction. “I like to re-volumize with filler before performing thread lifts to make sure that volume is restored, because you can’t really provide lift to someone with significant volume loss,” she said.
 

Procedural tips

Prior to the procedure, Dr. DiGiorgio marks the area to be treated while the patient is seated upright and holding a mirror. Then, she pulls back the amount of skin laxity the thread is going to correct. The plane of insertion for barbed threads is at the superficial musculoaponeurotic system (SMAS), and she typically uses 3-4 threads on each side of the face.

“How do you know you’re in the right plane?” If the patient is experiencing significant pain, “you’re too deep, and it’s not going to work,” she said. “You can see if the thread is too superficial as you do more of these.”

After the procedure she asks the patient to sit up prior to trimming the threads. “I take a look in the mirror with them and have them smile and make funny faces to see if there is any dimpling or crimpling, which is probably the most common side effect,” she said. “If I see that, I will pull the thread immediately, so we don’t have a problem. It’s a little uncomfortable to pull the thread but not more uncomfortable than the procedure itself, but I think it’s worth doing to avoid having a dimple or a crimple that can last up to a year.”

In her clinical experience, thread lifts last about 8-10 months. “I find that my patients will come in about once a year for this procedure, and the treated area feels tight afterward,” Dr. DiGiorgio said. “I think that sensation of feeling tight also provides satisfaction to the patient. Results are very subtle. It’s tissue repositioning; it is not a facelift. There’s not really any downtime, but further studies are required to see if threads are safe and effective in the long-term.”

In an interview after the meeting, she noted that the learning curve for thread lifts is variable, as with any new procedure a physician chooses to add to his or her practice. “It’s important to see these patients in follow-up 2 weeks after the procedure consistently, especially when someone first starts performing the procedure,” she recommended. “These patients are usually coming in to see me for other treatments, so I see them at regular 3-month intervals regardless. You begin to get a feel for what angles work and why and how to optimize the results. As with any procedure, the more experience you have performing the procedure will result in improved outcomes and improved management.”

Dr. DiGiorgio disclosed that she has been an advisory board member for Quthero and she holds stock options in the company. She is a consultant for Revelle and has received equipment from Acclaro.

Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.

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

Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.

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

Vitamin D deficiency appears to render people more vulnerable to canagliflozin’s adverse effects on bone health, whereas vitamin D3 supplementation appears protective of individuals with vitamin D deficiency.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are beneficial for treating type 2 diabetes and reducing cardiovascular and kidney disease risk. However, some, but not all, trial data have linked the SLGT2 inhibitor canagliflozin to increased fracture risk. That particular agent has been reported to accelerate loss of bone mineral density, which could contribute to fracture risk. Other drugs in the class have also been implicated in worsening markers of bone health.

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

Antidiabetic drug tirzepatide (Mounjaro) shows superiority over semaglutide (Ozempic, Wegovy, and Rybelsus) in controlling blood glucose as well as in the amount of weight lost, results from a meta-analysis of 22 randomized controlled trials show.

“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.

“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.

The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.

While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.

For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.

Overall, 18,472 participants were included in the studies.

All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
 

Blood glucose reduction

Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).

All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.

Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
 

Body weight reduction comparisons

The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).

In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
 

Adverse events: Increased GI events with highest tirzepatide dose

Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.

There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).

In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).

There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
 

Real-world applications, comparisons

Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.

“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.

Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.

Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.

Among other issues of comparison with the two drugs is cost.

In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.

Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.

Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.

Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.

Dr. Karagiannis reports no relevant financial relationships.

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

Antidiabetic drug tirzepatide (Mounjaro) shows superiority over semaglutide (Ozempic, Wegovy, and Rybelsus) in controlling blood glucose as well as in the amount of weight lost, results from a meta-analysis of 22 randomized controlled trials show.

“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.

“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.

The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.

While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.

For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.

Overall, 18,472 participants were included in the studies.

All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
 

Blood glucose reduction

Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).

All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.

Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
 

Body weight reduction comparisons

The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).

In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
 

Adverse events: Increased GI events with highest tirzepatide dose

Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.

There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).

In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).

There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
 

Real-world applications, comparisons

Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.

“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.

Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.

Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.

Among other issues of comparison with the two drugs is cost.

In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.

Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.

Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.

Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.

Dr. Karagiannis reports no relevant financial relationships.

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

Antidiabetic drug tirzepatide (Mounjaro) shows superiority over semaglutide (Ozempic, Wegovy, and Rybelsus) in controlling blood glucose as well as in the amount of weight lost, results from a meta-analysis of 22 randomized controlled trials show.

“The results indicate tirzepatide’s superior performance over subcutaneous semaglutide in managing blood sugar and achieving weight loss, making it a promising option in the pharmaceutical management of type 2 diabetes,” first author Thomas Karagiannis, MD, PhD, Aristotle University of Thessaloniki, Greece, said in an interview.

“In clinical context, the most potent doses of each drug revealed a clear difference regarding weight loss, with tirzepatide resulting in an average weight reduction that exceeded that of semaglutide by 5.7 kg (12.6 pounds),” he said.

The study is scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in early October.

While a multitude of studies have been conducted for tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist, and semaglutide, a selective GLP-1 agonist, studies comparing the two drugs directly are lacking.

For a more comprehensive understanding of how the drugs compare, Dr. Karagiannis and colleagues conducted the meta-analysis of 22 trials, including two direct comparisons, the SURPASS-2 trial and a smaller trial, and 20 other studies comparing either semaglutide or tirzepatide with a common comparator, such as placebo, basal insulin, or other GLP-RA-1 drugs.

Overall, 18,472 participants were included in the studies.

All included studies had assessed a maintenance dose of tirzepatide of either 5, 10, or 15 mg once weekly or semaglutide at doses of 0.5, 1.0, or 2.0 mg once weekly for at least 12 weeks. All comparisons were for subcutaneous injection formulations (semaglutide can also be taken orally).
 

Blood glucose reduction

Tirzepatide at 15 mg was found to have the highest efficacy in the reduction of A1c compared with placebo, with a mean difference of –2.00%, followed by tirzepatide 10 mg (–1.86%) and semaglutide 2.0 mg (–1.62%).

All three of the tirzepatide doses had greater reductions in A1c compared with the respective low, medium, and high doses of semaglutide.

Dr. Karagiannis noted that the differences are significant: “An A1c reduction even by 0.5% is often deemed clinically important,” he said.
 

Body weight reduction comparisons

The reductions in body weight across the three drug doses were greater with tirzepatide (–10.96 kg [24.2 pounds], –8.75 kg [19.3 pounds], and –6.16 kg [13.6 pounds] for 15, 10, and 5 mg, respectively) compared with semaglutide (–5.24 kg [11.6 pounds], –4.44 kg [9.8 pounds], and –2.72 kg [6 pounds] for semaglutide 2.0, 1.0, and 0.5 mg, respectively).

In terms of drug-to-drug comparisons, tirzepatide 15 mg had a mean of 5.72 kg (12.6 pounds) greater reduction in body weight vs. semaglutide 2.0 mg; tirzepatide 10 mg had a mean of 3.52 kg (7.8 pounds) reduction vs. semaglutide 2.0 mg; and tirzepatide 5 mg had a mean of a 1.72 kg (3.8 pounds) greater reduction vs. semaglutide 1.0 mg.
 

Adverse events: Increased GI events with highest tirzepatide dose

Regarding the gastrointestinal adverse events associated with the drugs, tirzepatide 15 mg had the highest rate of the two drugs at their various doses, with a risk ratio (RR) of 3.57 compared with placebo for nausea, an RR of 4.35 for vomiting, and 2.04 for diarrhea.

There were no significant differences between the two drugs for the gastrointestinal events, with the exception of the highest dose of tirzepatide, 15 mg, which had a higher risk of vomiting vs. semaglutide 1.0 (RR 1.39) and semaglutide 0.5 mg (RR 1.85).

In addition, tirzepatide 15 mg had a higher risk vs. semaglutide 0.5 mg for nausea (RR 1.45).

There were no significant differences between the two drugs and placebo in the risk of serious adverse events.
 

Real-world applications, comparisons

Dr. Karagiannis noted that the results indicate that benefits of the efficacy of the higher tirzepatide dose need to be balanced with those potential side effects.

“Although the efficacy of the high tirzepatide dose might make it a favorable choice, its real-world application can be affected on an individual’s ability to tolerate these side effects in case they occur,” he explained.

Ultimately, “some patients may prioritize tolerability over enhanced efficacy,” he added.

Furthermore, while all three maintenance doses of tirzepatide analyzed have received marketing authorization, “to get a clearer picture of the real-world tolerance to these doses outside the context of randomized controlled trials, well-designed observational studies would be necessary,” Dr. Karagiannis said.

Among other issues of comparison with the two drugs is cost.

In a recent analysis, the cost per 1% of body weight reduction was reported to be $1,197 for high-dose tirzepatide (15 mg) vs. $1,511 for semaglutide 2.4 mg, with an overall cost of 72 weeks of therapy with tirzepatide at $17,527 compared with $22,878 for semaglutide.

Overall, patients and clinicians should consider the full range of differences and similarities between the medications, “from [their] efficacy and side effects to cost-effectiveness, long-term safety, and cardiovascular profile,” Dr. Karagiannis said.

Semaglutide is currently approved by the Food and Drug Administration for treatment of type 2 diabetes and obesity/weight loss management.

Tirzepatide has also received approval for the treatment of type 2 diabetes and its manufacturers have submitted applications for its approval for obesity/weight loss management.

Dr. Karagiannis reports no relevant financial relationships.

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

LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.

“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”

“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.

While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
 

‘Inflamm-aging’

“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.

As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.

The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.

With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.

This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
 

‘Bad old T cells’

Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”

In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
 

Power sources fail

In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”

At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.

T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”

Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
 

Inflammatory cell death

In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”

In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.

Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”

Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.

When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”

This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.

LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.

“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”

“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.

While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
 

‘Inflamm-aging’

“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.

As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.

The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.

With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.

This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
 

‘Bad old T cells’

Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”

In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
 

Power sources fail

In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”

At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.

T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”

Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
 

Inflammatory cell death

In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”

In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.

Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”

Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.

When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”

This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.

LEIPZIG, GERMANY – With age comes illness: Cancer, cardiovascular and neurodegenerative diseases, increased infections, and autoimmune diseases such as rheumatism become more common. This is because the immune system also ages. In the case of autoimmune diseases, this aging happens particularly quickly.

“There is this phenomenon of premature aging of the immune system,” said Cornelia Weyand, PhD, director of Stanford (Calif.) University’s Center for Translational Medicine at the German Rheumatology Congress 2023. In healthy people, the immune system begins to age at age 20. From that point on, the thymus gland, which reaches peak function at 14-15 years old, plays an increasingly minor role. “At age 50 years, the aging process of the immune system gains momentum.”

“What’s good about this is that the T and B cells age together, but all a little differently, each system by itself,” said Thomas Dörner, MD, PhD, head of consultation hours for clinical hemostaseology at the Charité University Hospitals in Berlin.

While the reduced formation of naive T cells can be attributed to the regression of the thymus gland, the naive B cells are a consequence of age-related, fatty bone marrow degeneration. The influence of adipocyte-derived tumor necrosis factor (TNF)–alpha also causes the bone marrow to develop B cells more and more weakly and slowly. “Through this [process], the preimmune range of B-cells decreases and becomes less healthy than in a young person.”
 

‘Inflamm-aging’

“In the periphery, we have identified a process we call “inflamm-aging,” where the cytokines interferon-gamma, interleukin (IL)–10, and IL-17 play a predominant role. This also alters the primary and secondary immune response,” said Dr. Dörner. Here, decreasing stimulation via the B-cell receptor by aging T-lymphocytes makes a difference.

As we age, the immune system restructures itself completely. “Protective immunity regresses and the inferior immunity emerges,” explained Dr. Weyand. Wounds heal more poorly, the protective action against infections and above all malignancies, as well as the immune response to vaccinations, decreases.

The increased occurrence of neurodegenerative, cardiovascular, and autoimmune diseases is not because of a loss of function, but rather to newly gained, undesired functions. These are associated with inflammatory changes. Hence, the term inflamm-aging.

With the B cells, functional germinal centers in the lymphoid organs and protective antibodies become rarer, and age-associated B cells accumulate. As Dr. Dörner emphasized, these cells are not under the command of the B-cell receptor and are independent of the cytokine BAFF (B-cell activating factor). Instead, they react to signals that are sent from the toll-like receptors 7 and 9.

This potentially also explains the increased development of autoantibodies in older people and the association of viral and autoimmune diseases. This means that age-associated B cells develop more frequently, such as with rheumatoid arthritis, scleroderma, and systemic lupus erythematosus. “There are good data that show that they are triggered by infections and that they are specialized to form autoantibodies,” Dr. Weyand said about the age-associated B cells.
 

‘Bad old T cells’

Under the influence of genetic stop-and-go signals, the composition of the T-cell population also changes over the course of our lives. It becomes less diverse. T-helper cells become less common, and as a result, terminally differentiated effector memory T cells become more common. According to Dr. Weyand, herein lies the problem. “These cells are not just lazy, old cells that sit around. Unfortunately, they are also malicious. What we see in both the T- and B-cell systems is that they become increasingly innate with age,” he said. “They are not quite so precise or good.”

In turn, myeloid cells are less active in old age because of phagocytosis and antigen presentation, and they get more mutations. They are released more often from the bone marrow, produce more cytokines, and essentially contribute to inflamm-aging.
 

Power sources fail

In her cellular and microbiological investigations, Dr. Weyand has devoted a lot of time to studying why T cells age prematurely in patients with RA. The key was in the cellular microbiology. “We learned how the T-cell aging process translates into metabolic reprogramming of the T cells – how a good, strong, and protective T cell transforms into a disease-inducing T cell.”

At the center of premature T-cell aging in RA are disrupted mitochondrial function and insufficient communication of the mitochondria with the lysosomes and the endoplasmic reticulum.

T cells of RA patients (RA T cells) contain less MRE11A, compared with those in healthy people. This is a nuclease that allows the repair of breaks in DNA. If MRE11A is inhibited, then senescent T cells accumulate and form proinflammatory cytokines such as IL-B, IL-6, and TNF. “This is the trio that we rheumatologists are always concerned with.”

Since mitochondrial DNA repair is essential for maintaining mitochondrial fitness, the cellular power sources in patients with RA cannot provide as much energy in the form of adenosine triphosphate as in healthy people. Metabolically, they are not so fit, Dr. Weyand said.
 

Inflammatory cell death

In fact, all metabolic pathways in the T cells are reduced. The bioenergetic failure has consequences. “Unfortunately, as the mitochondrion ages, its DNA leaks into the cytosol,” explained Dr. Weyand. “Cells do not like this.” This is because DNA activates inflammasomes in the cytosol via caspase-1. This process results in a highly inflammatory cell death: pyroptosis. Subsequently, there is no trace of the cells in the tissue. “RA patients’ synovial tissue is a graveyard of dying T cells.”

In the lysosomes, the cells’ “intestine,” problems arise because patients with RA can no longer activate the adenosine monophosphate–activated protein kinase enzyme. It does not receive the lipid tail it needs to take its position as energy sensor on the lysosomal membrane. As a result, its antagonist, mTOR – both usually keep each other in check – gains the upper hand. According to Dr. Weyand, “mTOR has a party.” It activates and stresses the cells.

Additional changes affect the endoplasmic reticulum (ER). “This is where all of your proteins are synthesized and packaged to migrate from within to outside the cell, or to the cell membrane.” Compared with healthy T cells, RA T cells have around 50% more ER. “The less that mitochondria work, the larger the ER. It gets really fat.”

Mitochondria communicate with the ER via aspartate, oxaloacetate, and malate. In so doing, they control their size. RA T cells appear to be aspartate deficient. In animal models, amino acids had an anti-inflammatory effect.

When sequencing the mRNA bound to the ER, Dr. Weyand and her colleagues encountered the building blocks for TNF. “There is more than three times as much mRNA as TNF. It transforms these T cells into TNF superproducers,” said the rheumatologist. “No wonder this kind of cell is proinflammatory – it forms precisely that cytokine on which you focus every day.”

This article was translated from Medscape’s German edition. A version of this article first appeared on Medscape.com.

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

What if cardiology were no longer an internal medicine subspecialty? Four leading cardiology societies have announced plans to create a new certification process that is independent of the American Board of Internal Medicine maintenance of certification (MOC) system.

As envisioned, the new “independent, self-governed” entity would supplant the ABIM’s long-standing and widely criticized MOC system and establish cardiology as its own specialty with its own subspecialties. Long in coming, it is only the latest response to many in the field who for years have charged that the MOC system is needlessly burdensome and expensive.

“It’s time to have a dedicated cardiovascular medicine board of our own,” said B. Hadley Wilson, MD, in the group’s announcement. “Cardiology is a distinct medical specialty, and physicians want and deserve a clinical competency and continuous certification program that is meaningful to their practice and patients.”

Hadley Wilson, Sanger Heart & Vascular Institute Vascular Kenilworth, Charlotte, N.C., is president of the American College of Cardiology, one of the four societies spearheading the initiative along with the Heart Failure Society of America, the Heart Rhythm Society, and the Society for Cardiovascular Angiography & Interventions.

Their Sept. 21 statement says that the consortium will apply to the American Board of Medical Specialties to request an independent cardiology board that follows a “new competency-based approach to continuous certification – one that harnesses the knowledge, skills, and attitudes required to sustain professional excellence and care for cardiovascular patients effectively.”

It continues, “The new board requirements will de-emphasize timed, high stakes performance exams in the continuous certification process and instead will focus on learning assessments to identify gaps in current knowledge or skills.”

“The new board’s focus on competence in the pursuit of continuous certification is a needed paradigm shift for the field,” states HFSA President John R. Teerlink, MD, University of California, San Francisco, and the San Francisco VA Medical Center, in the announcement.

“I commend these professional cardiovascular societies for taking on this important challenge,” Deepak L. Bhatt, MD, MPH, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai, New York City, told this news organization by email.

“This is an incredible opportunity to redefine what ongoing cardiovascular education means to the contemporary practicing cardiologist in a way that is relevant to improving the care of actual patients,” said Dr. Bhatt, who chairs the ACC Accreditation Oversight Committee.

“There needs to be an agile, personalized, convenient, and effective system to assist practitioners to stay current with new knowledge and demonstrate the necessary competencies,” Harlan Krumholz, MD, said in an email.

“There is a deep sense in the profession that the current approaches do not meet the needs of clinicians or society,” said Dr. Krumholz, Yale School of Medicine, New Haven, Conn., who has sat on the ABIM board of directors.

“This effort, which now will create competition, has the potential to spark innovation,” he said. “The key is that any approach needs to ask the question, ‘Is the cost and effort producing benefit for patients and society?’ If it is not, we have not found the right system.”

In a statement in response to the new development, ABIM said it plans to continue “offering and administering” its existing MOC programs across all specialties.

“Any physician choosing to maintain their ABIM certification in these disciplines will continue to have a pathway with ABIM to do so,” it says. “Questions about the cardiovascular organizations’ announcement and how it may affect individual physicians are best answered by those organizations.”

The process of approving the heart societies’ application to ABMS “is expected to take several months,” their announcement states. If approval is granted, “it will then take several additional months before initial certification and continuous certification and competency programs would begin.”

Medscape provides educational content including MOC. Medscape’s editorial content, including news and features, is developed independently of the educational content available on Medscape.

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

AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.

“MPI provides incremental prognostic information” in people with type 1 diabetes that “may enhance risk prediction” for their future risk of all-cause death, acute coronary syndrome, heart failure, or stroke, Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.

The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.

Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
 

‘Trying to figure out’ the type 1 diabetes link

“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.

The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.

The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.

This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.

Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
 

MPI reflects left ventricular function

MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.

“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”

The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.

The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.

“MPI provides incremental prognostic information” in people with type 1 diabetes that “may enhance risk prediction” for their future risk of all-cause death, acute coronary syndrome, heart failure, or stroke, Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.

The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.

Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
 

‘Trying to figure out’ the type 1 diabetes link

“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.

The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.

The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.

This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.

Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
 

MPI reflects left ventricular function

MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.

“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”

The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.

The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

AMSTERDAM – Calculating a patient’s myocardial performance index (MPI) and adding it to a standard risk-prediction model significantly increased prognostic accuracy for major adverse cardiovascular events (MACE), especially heart failure, in people with type 1 but not type 2 diabetes, an analysis of data from about 2,000 Danish patients shows.

“MPI provides incremental prognostic information” in people with type 1 diabetes that “may enhance risk prediction” for their future risk of all-cause death, acute coronary syndrome, heart failure, or stroke, Hashmat S.Z. Bahrami, MD, said at the annual congress of the European Society of Cardiology.

The primary analysis he reported showed a significantly elevated adjusted hazard ratio of 1.2 among people with either type 1 or type 2 diabetes and an elevated MPI, compared with those with diabetes but a lower MPI value.

Further analysis divided the study cohort into the 1,093 people with type 1 diabetes and the 1,030 with type 2 diabetes and showed that the significant association of elevated MPI with increased MACE was entirely confined to the type 1 diabetes subgroup, again with a hazard ratio of 1.2, but without any significant association among those with type 2 diabetes, said Dr. Bahrami, a cardiology researcher at Copenhagen University Hospital.
 

‘Trying to figure out’ the type 1 diabetes link

“We’re still trying to figure out” the explanation for this difference based on diabetes type, Dr. Bahrami said. He speculated that it might relate to a higher incidence of heart failure among those with type 1 diabetes, or to longer duration of diabetes in the type 1 subgroup.

The ability of elevated MPI to predict an increased risk specifically for heart failure was apparent in another analysis he presented that divided MACE events into the individual components of this composite. Elevated MPI significantly linked with a 1.3-fold elevated risk for heart failure in those with type 1 diabetes, but high MPI had no significant association with any of the other event types included in the MACE composite.

The researchers also assessed the incremental impact from adding MPI data to an established cardiovascular disease (CVD) risk calculator for people with type 1 diabetes, the Steno Type 1 Risk Engine, which includes nine parameters such as age, sex, blood pressure, diabetes duration, and two different measures of renal function.

This analysis showed that adding MPI significantly boosted the attributable CVD risk from an area-under-the-curve of 0.77 to an AUC of 0.79. Including MPI also boosted the AUC for risk of future heart failure from 0.77 with the existing Steno Type 1 Risk Engine to 0.83, also a significant increase.

Simultaneously with his talk at the Congress, a report on the findings was published online in the European Heart Journal Cardiovascular Imaging.
 

MPI reflects left ventricular function

MPI is calculated by adding a person’s isovolumic cardiac relaxation time to their isovolumic cardiac contraction time and dividing this by their ejection time. These time measurements come from examination with tissue Doppler M-mode echocardiography, Dr. Bahrami explained, and when assessed together reflect left ventricular function during both systolic and diastolic phases.

“MPI has been around for many years, but our technique is rather novel” and has high intra- and inter-observer reproducibility, he said. “It’s highly reproducible and feasible.”

The study included data collected prospectively from Danish adults without any known CVD enrolled in the Thousand & 1 study of people with type 1 diabetes and the Thousand & 2 study of people with type 2 diabetes. The analyses that Dr. Bahrami reported included CVD events during a median 5.3 years of follow-up.

The study received funding from Novo Nordisk. Dr. Bahrami has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

When patients seek primary care, it’s becoming more likely that they’ll see a nurse practitioner or physician assistant.

Health care visits to NPs and PAs, also known as advanced practice providers, have been rising in recent years compared with doctor visits, according to the latest studies. The proportion of Medicare visits that NPs and PAs delivered nearly doubled in the 7-year period 2013-2019 (14% in 2013 to 26% in 2019), according to research published this month in the BMJ. Among study participants, 42% had at least one visit with an NP or PA. Meanwhile, primary care visits with a physician decreased by 18%, the study showed.

Medicare accounts for roughly 20% of the U.S. population and 23% of health care spending, according to 2023 data cited in the report. Study authors surveyed a random sample, 20% of Medicare recipients who sought care through in-person and telemedicine visits to outpatient and nursing facilities before the COVID-19 pandemic.

Medical clinics have turned to NPs and PAs to offset a shortage of primary care doctors, with the United States having fewer physicians per capita than other industrialized nations, according to Ateev Mehrotra, MD, MPH, professor of health care policy at Harvard Medical School and one of the authors of the BMJ report.

Nursing schools also struggle to meet the growing demand for NPs. In more than half of U.S. states, NPs can work independently without physician supervision, while PAs face more restrictions.

Another study earlier this year also found a rise in APP care. FAIR Health reported that nearly one in three patients received care between 2016 and 2022 from someone other than a physician, with NPs providing 27% of primary care visits and PAs, 15%.

The trend isn’t new. But for many years, claims data from Medicare or commercial payers masked the impact of advanced practitioners because their care was billed under a supervising physician, explained Michael L. Powe, vice president of reimbursement and professional advocacy for the American Academy of Physician Assistants, which represents PAs.

NPs and PAs are more likely to see patients with lower incomes, those who live in rural communities, or those who have disabilities, according to the BMJ study, suggesting that these providers may improve access to health care.

They already comprise about half of the primary care professionals in rural areas, said Stephen Ferrara, DNP, president of the American Association of Nurse Practitioners, citing a 2022 report by the Medicare Payment Advisory Commission.

The BMJ study also found that NPs and PAs were more likely to see patients for certain conditions. For example, they handled 42% of visits for respiratory infections and 37% of visits for anxiety, compared with only 13% of visits for eye problems and 20% of visits for hypertension.

Dr. Mehrotra said patients, in general, are still unlikely to see only an NP for many conditions, particularly chronic illness. “You might see the physician one time and then the nurse practitioner, and then the PA. And you might see another physician in the practice.”

He said health care leaders need to decide how to set up teams to best serve patients. From a health policy perspective, they should also consider whether to boost funding for NP and PA education or primary care residencies.

Meanwhile, the growth of advanced practitioners continues. The Bureau of Labor Statistics estimates that the number of NPs will increase to 359,000 in 2031 (80% growth from 2019) and the number of PAs will increase to 178,000 (48% growth).
 

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

When patients seek primary care, it’s becoming more likely that they’ll see a nurse practitioner or physician assistant.

Health care visits to NPs and PAs, also known as advanced practice providers, have been rising in recent years compared with doctor visits, according to the latest studies. The proportion of Medicare visits that NPs and PAs delivered nearly doubled in the 7-year period 2013-2019 (14% in 2013 to 26% in 2019), according to research published this month in the BMJ. Among study participants, 42% had at least one visit with an NP or PA. Meanwhile, primary care visits with a physician decreased by 18%, the study showed.

Medicare accounts for roughly 20% of the U.S. population and 23% of health care spending, according to 2023 data cited in the report. Study authors surveyed a random sample, 20% of Medicare recipients who sought care through in-person and telemedicine visits to outpatient and nursing facilities before the COVID-19 pandemic.

Medical clinics have turned to NPs and PAs to offset a shortage of primary care doctors, with the United States having fewer physicians per capita than other industrialized nations, according to Ateev Mehrotra, MD, MPH, professor of health care policy at Harvard Medical School and one of the authors of the BMJ report.

Nursing schools also struggle to meet the growing demand for NPs. In more than half of U.S. states, NPs can work independently without physician supervision, while PAs face more restrictions.

Another study earlier this year also found a rise in APP care. FAIR Health reported that nearly one in three patients received care between 2016 and 2022 from someone other than a physician, with NPs providing 27% of primary care visits and PAs, 15%.

The trend isn’t new. But for many years, claims data from Medicare or commercial payers masked the impact of advanced practitioners because their care was billed under a supervising physician, explained Michael L. Powe, vice president of reimbursement and professional advocacy for the American Academy of Physician Assistants, which represents PAs.

NPs and PAs are more likely to see patients with lower incomes, those who live in rural communities, or those who have disabilities, according to the BMJ study, suggesting that these providers may improve access to health care.

They already comprise about half of the primary care professionals in rural areas, said Stephen Ferrara, DNP, president of the American Association of Nurse Practitioners, citing a 2022 report by the Medicare Payment Advisory Commission.

The BMJ study also found that NPs and PAs were more likely to see patients for certain conditions. For example, they handled 42% of visits for respiratory infections and 37% of visits for anxiety, compared with only 13% of visits for eye problems and 20% of visits for hypertension.

Dr. Mehrotra said patients, in general, are still unlikely to see only an NP for many conditions, particularly chronic illness. “You might see the physician one time and then the nurse practitioner, and then the PA. And you might see another physician in the practice.”

He said health care leaders need to decide how to set up teams to best serve patients. From a health policy perspective, they should also consider whether to boost funding for NP and PA education or primary care residencies.

Meanwhile, the growth of advanced practitioners continues. The Bureau of Labor Statistics estimates that the number of NPs will increase to 359,000 in 2031 (80% growth from 2019) and the number of PAs will increase to 178,000 (48% growth).
 

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

When patients seek primary care, it’s becoming more likely that they’ll see a nurse practitioner or physician assistant.

Health care visits to NPs and PAs, also known as advanced practice providers, have been rising in recent years compared with doctor visits, according to the latest studies. The proportion of Medicare visits that NPs and PAs delivered nearly doubled in the 7-year period 2013-2019 (14% in 2013 to 26% in 2019), according to research published this month in the BMJ. Among study participants, 42% had at least one visit with an NP or PA. Meanwhile, primary care visits with a physician decreased by 18%, the study showed.

Medicare accounts for roughly 20% of the U.S. population and 23% of health care spending, according to 2023 data cited in the report. Study authors surveyed a random sample, 20% of Medicare recipients who sought care through in-person and telemedicine visits to outpatient and nursing facilities before the COVID-19 pandemic.

Medical clinics have turned to NPs and PAs to offset a shortage of primary care doctors, with the United States having fewer physicians per capita than other industrialized nations, according to Ateev Mehrotra, MD, MPH, professor of health care policy at Harvard Medical School and one of the authors of the BMJ report.

Nursing schools also struggle to meet the growing demand for NPs. In more than half of U.S. states, NPs can work independently without physician supervision, while PAs face more restrictions.

Another study earlier this year also found a rise in APP care. FAIR Health reported that nearly one in three patients received care between 2016 and 2022 from someone other than a physician, with NPs providing 27% of primary care visits and PAs, 15%.

The trend isn’t new. But for many years, claims data from Medicare or commercial payers masked the impact of advanced practitioners because their care was billed under a supervising physician, explained Michael L. Powe, vice president of reimbursement and professional advocacy for the American Academy of Physician Assistants, which represents PAs.

NPs and PAs are more likely to see patients with lower incomes, those who live in rural communities, or those who have disabilities, according to the BMJ study, suggesting that these providers may improve access to health care.

They already comprise about half of the primary care professionals in rural areas, said Stephen Ferrara, DNP, president of the American Association of Nurse Practitioners, citing a 2022 report by the Medicare Payment Advisory Commission.

The BMJ study also found that NPs and PAs were more likely to see patients for certain conditions. For example, they handled 42% of visits for respiratory infections and 37% of visits for anxiety, compared with only 13% of visits for eye problems and 20% of visits for hypertension.

Dr. Mehrotra said patients, in general, are still unlikely to see only an NP for many conditions, particularly chronic illness. “You might see the physician one time and then the nurse practitioner, and then the PA. And you might see another physician in the practice.”

He said health care leaders need to decide how to set up teams to best serve patients. From a health policy perspective, they should also consider whether to boost funding for NP and PA education or primary care residencies.

Meanwhile, the growth of advanced practitioners continues. The Bureau of Labor Statistics estimates that the number of NPs will increase to 359,000 in 2031 (80% growth from 2019) and the number of PAs will increase to 178,000 (48% growth).
 

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

TOPLINE:

Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.

METHODOLOGY:

• Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
• Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
• The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.

TAKEAWAY:

• Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
• Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
• The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
• Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.

IN PRACTICE:

The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.

SOURCE:

First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.

LIMITATIONS:

More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.

DISCLOSURES:

The study received no outside funding. The researchers report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.

METHODOLOGY:

• Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
• Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
• The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.

TAKEAWAY:

• Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
• Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
• The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
• Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.

IN PRACTICE:

The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.

SOURCE:

First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.

LIMITATIONS:

More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.

DISCLOSURES:

The study received no outside funding. The researchers report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Blood samples from healthy adults show an inhibition of neutrophil extracellular trap formation (NET) after 1 week of daily ginger supplements.

METHODOLOGY:

• Researchers recruited nine healthy adults aged 18-38 years to receive a 100-mg oral ginger supplement daily for 7 consecutive days.
• Blood samples were collected at baseline and on days 7 and 14, with isolation of neutrophils, peripheral blood mononuclear cells, and plasma.
• The researchers measured NET formation (NETosis) as a way to show the effect of ginger on inflammation.

TAKEAWAY:

• Measures of neutrophil cyclic AMP (cAMP) were significantly higher after 7 days of ginger supplements, compared with baseline levels, although these levels returned to near baseline by 1 week after discontinuing ginger consumption.
• Oral ginger supplements reduced neutrophil phosphodiesterase (PDE) activity by 40% from baseline, similar to results seen with synthetic PDE4 inhibitors.
• The results build on previous studies showing inhibition of neutrophil hyperactivity in mice with antiphospholipid syndrome and lupus after injection with a purified ginger preparation.
• Researchers replicated the results showing effects of oral ginger on neutrophils in eight additional healthy adults who also showed reduced NETosis and increased cAMP after 1 week of ginger supplements.

IN PRACTICE:

The results show biologic support for the potential of ginger to affect neutrophil function in humans; therefore, “ginger may have a real ability to complement treatment programs that are already underway,” said corresponding author Jason Knight, MD, of the University of Michigan, Ann Arbor, in a press release.

SOURCE:

First author Ramadan A. Ali, MD, of the University of Michigan, Ann Arbor, and colleagues reported their study in JCI Insight.

LIMITATIONS:

More research is needed in humans with inflammatory and autoimmune diseases to confirm the findings and explore ginger as an adjuvant therapeutic intervention.

DISCLOSURES:

The study received no outside funding. The researchers report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3

Key clinical point: Fremanezumab was effective as a preventive treatment in patients with chronic migraine (CM) with or without medication overuse (MO) and showed potential benefits in reducing MO.

Major finding: During a 12-week follow-up period, the administration of monthly and quarterly fremanezumab vs placebo led to significantly reduced average number of monthly headache days of moderate or greater severity in patients with MO (monthly: mean change [∆] −2.0, P = .0012; and quarterly: ∆ −1.8, P = .0042) and without MO (monthly: ∆ −1.6, P = .0437; and quarterly: ∆ −1.5, P = .0441). A greater proportion of patients receiving fremanezumab vs placebo reverted to no MO (P ≤ .05).

Study details: This post hoc analysis of a phase 2b/3 trial included 479 Japanese patients with CM who were randomly assigned to receive monthly fremanezumab (n = 159), quarterly fremanezumab (n = 159), or placebo (n = 161), and of whom 320 patients reported MO.

Disclosures: This study was funded by Otsuka Pharmaceutical Co., Ltd. Several authors declared being full-time employees of Otsuka Pharmaceutical Co., Ltd., and N Imai declared ties with various other sources.

Source: Imai N et al. Effects of fremanezumab on medication overuse in Japanese chronic migraine patients: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. Neurol Ther. 2023 (Sep 11). doi: 10.1007/s40120-023-00531-3