Imaging

Patients with anorexia nervosa (AN) have notable shrinkage in key brain structures and these deficits are less severe in patients on the path to weight recovery, a new brain imaging study shows.

The reductions of cortical thickness, subcortical volumes, and cortical surface area were “very pronounced in acutely underweight anorexia,” Stefan Ehrlich, MD, PhD, head of the Eating Disorder Treatment and Research Center, Technical University, Dresden, Germany, told this news organization.

Yet even a “partial weight gain brings some normalization of these shrinkages. From this it can be deduced that a fast/early normalization of weight is also very important for brain health,” said Dr. Ehrlich.

The study was published online in Biological Psychiatry.
 

‘A wake-up call’

Researchers with the international ENIGMA Eating Disorders Working Group analyzed T1-weighted structural magnetic resonance imaging scans for nearly 2,000 people with AN (including those in recovery) and healthy controls across 22 sites worldwide.

In the AN sample, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were “sizable (Cohen’s d up to 0.95), widespread, and co-localized with hub regions,” they report.

These reductions were two and four times larger than the abnormalities in brain size and shape seen in patients with other mental illnesses, the researchers note.

Noting the harmful impact of anorexia-related undernutrition on the brain, these deficits were associated with lower body mass index in the AN sample and were less severe in partially weight-restored patients – implying that, with appropriate early treatment and support, the brain might be able to repair itself, the investigators note.

“This really is a wake-up call, showing the need for early interventions for people with eating disorders,” Paul Thompson, PhD, author and lead scientist for the ENIGMA Consortium, said in a news release.

“The international scale of this work is extraordinary. Scientists from 22 centers worldwide pooled their brain scans to create the most detailed picture to date of how anorexia affects the brain,” Dr. Thompson added.

“The brain changes in anorexia were more severe than in other any psychiatric condition we have studied. Effects of treatments and interventions can now be evaluated, using these new brain maps as a reference,” he noted.
 

Immediate clinical implications

Reached for comment, Allison Eliscu, MD, chief of the division of adolescent medicine, department of pediatrics, at Stony Brook (N.Y.) University, said the findings have immediate implications for clinical care.

“When we talk to our patients and the parents, a lot of them focus on things that they can see, such as the way they look. It adds a lot to the conversation to be able to say: You’re obviously not seeing these changes in the brain, but they’re happening and could be potentially long term if you don’t start weight restoring, or if you weight restore and then continue to drop again,” Dr. Eliscu said in an interview.

The findings, she said, really do highlight what anorexia can do to the brain.

“Adolescents need to know, anorexia can absolutely decrease the size of your brain in different areas; you’re not just losing weight in your belly and your thighs, you’re losing weight in the brain as well and that’s really concerning,” said Dr. Eliscu.

The study had no commercial funding. The authors and Dr. Eliscu report no relevant conflicts of interest.

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

Patients with anorexia nervosa (AN) have notable shrinkage in key brain structures and these deficits are less severe in patients on the path to weight recovery, a new brain imaging study shows.

The reductions of cortical thickness, subcortical volumes, and cortical surface area were “very pronounced in acutely underweight anorexia,” Stefan Ehrlich, MD, PhD, head of the Eating Disorder Treatment and Research Center, Technical University, Dresden, Germany, told this news organization.

Yet even a “partial weight gain brings some normalization of these shrinkages. From this it can be deduced that a fast/early normalization of weight is also very important for brain health,” said Dr. Ehrlich.

The study was published online in Biological Psychiatry.
 

‘A wake-up call’

Researchers with the international ENIGMA Eating Disorders Working Group analyzed T1-weighted structural magnetic resonance imaging scans for nearly 2,000 people with AN (including those in recovery) and healthy controls across 22 sites worldwide.

In the AN sample, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were “sizable (Cohen’s d up to 0.95), widespread, and co-localized with hub regions,” they report.

These reductions were two and four times larger than the abnormalities in brain size and shape seen in patients with other mental illnesses, the researchers note.

Noting the harmful impact of anorexia-related undernutrition on the brain, these deficits were associated with lower body mass index in the AN sample and were less severe in partially weight-restored patients – implying that, with appropriate early treatment and support, the brain might be able to repair itself, the investigators note.

“This really is a wake-up call, showing the need for early interventions for people with eating disorders,” Paul Thompson, PhD, author and lead scientist for the ENIGMA Consortium, said in a news release.

“The international scale of this work is extraordinary. Scientists from 22 centers worldwide pooled their brain scans to create the most detailed picture to date of how anorexia affects the brain,” Dr. Thompson added.

“The brain changes in anorexia were more severe than in other any psychiatric condition we have studied. Effects of treatments and interventions can now be evaluated, using these new brain maps as a reference,” he noted.
 

Immediate clinical implications

Reached for comment, Allison Eliscu, MD, chief of the division of adolescent medicine, department of pediatrics, at Stony Brook (N.Y.) University, said the findings have immediate implications for clinical care.

“When we talk to our patients and the parents, a lot of them focus on things that they can see, such as the way they look. It adds a lot to the conversation to be able to say: You’re obviously not seeing these changes in the brain, but they’re happening and could be potentially long term if you don’t start weight restoring, or if you weight restore and then continue to drop again,” Dr. Eliscu said in an interview.

The findings, she said, really do highlight what anorexia can do to the brain.

“Adolescents need to know, anorexia can absolutely decrease the size of your brain in different areas; you’re not just losing weight in your belly and your thighs, you’re losing weight in the brain as well and that’s really concerning,” said Dr. Eliscu.

The study had no commercial funding. The authors and Dr. Eliscu report no relevant conflicts of interest.

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

Patients with anorexia nervosa (AN) have notable shrinkage in key brain structures and these deficits are less severe in patients on the path to weight recovery, a new brain imaging study shows.

The reductions of cortical thickness, subcortical volumes, and cortical surface area were “very pronounced in acutely underweight anorexia,” Stefan Ehrlich, MD, PhD, head of the Eating Disorder Treatment and Research Center, Technical University, Dresden, Germany, told this news organization.

Yet even a “partial weight gain brings some normalization of these shrinkages. From this it can be deduced that a fast/early normalization of weight is also very important for brain health,” said Dr. Ehrlich.

The study was published online in Biological Psychiatry.
 

‘A wake-up call’

Researchers with the international ENIGMA Eating Disorders Working Group analyzed T1-weighted structural magnetic resonance imaging scans for nearly 2,000 people with AN (including those in recovery) and healthy controls across 22 sites worldwide.

In the AN sample, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were “sizable (Cohen’s d up to 0.95), widespread, and co-localized with hub regions,” they report.

These reductions were two and four times larger than the abnormalities in brain size and shape seen in patients with other mental illnesses, the researchers note.

Noting the harmful impact of anorexia-related undernutrition on the brain, these deficits were associated with lower body mass index in the AN sample and were less severe in partially weight-restored patients – implying that, with appropriate early treatment and support, the brain might be able to repair itself, the investigators note.

“This really is a wake-up call, showing the need for early interventions for people with eating disorders,” Paul Thompson, PhD, author and lead scientist for the ENIGMA Consortium, said in a news release.

“The international scale of this work is extraordinary. Scientists from 22 centers worldwide pooled their brain scans to create the most detailed picture to date of how anorexia affects the brain,” Dr. Thompson added.

“The brain changes in anorexia were more severe than in other any psychiatric condition we have studied. Effects of treatments and interventions can now be evaluated, using these new brain maps as a reference,” he noted.
 

Immediate clinical implications

Reached for comment, Allison Eliscu, MD, chief of the division of adolescent medicine, department of pediatrics, at Stony Brook (N.Y.) University, said the findings have immediate implications for clinical care.

“When we talk to our patients and the parents, a lot of them focus on things that they can see, such as the way they look. It adds a lot to the conversation to be able to say: You’re obviously not seeing these changes in the brain, but they’re happening and could be potentially long term if you don’t start weight restoring, or if you weight restore and then continue to drop again,” Dr. Eliscu said in an interview.

The findings, she said, really do highlight what anorexia can do to the brain.

“Adolescents need to know, anorexia can absolutely decrease the size of your brain in different areas; you’re not just losing weight in your belly and your thighs, you’re losing weight in the brain as well and that’s really concerning,” said Dr. Eliscu.

The study had no commercial funding. The authors and Dr. Eliscu report no relevant conflicts of interest.

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

A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.

Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).

After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.

“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”

Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:

• Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
• Stent thrombosis: 30.9% vs. 34.9% (P < .01).
• Long lesions: 13.1% vs. 16.3% (P < .01).
• Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
• Left main stem PCI: 55.1% vs. 57.5% (P < .01).
• In-stent restenosis: 28.0% vs. 30.7%.
• Calcified lesions: 36.6% vs. 40.1% (P < .01).
• Renal disease: 17.4% vs. 19.5% (P < .01).

As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.

“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”

Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.

“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.

“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
 

Getting worse, not better

Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.

To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.

Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.

One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.

“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.

Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.

“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”

Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.

“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”

Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.

“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”

Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.

“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.

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

A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.

Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).

After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.

“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”

Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:

• Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
• Stent thrombosis: 30.9% vs. 34.9% (P < .01).
• Long lesions: 13.1% vs. 16.3% (P < .01).
• Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
• Left main stem PCI: 55.1% vs. 57.5% (P < .01).
• In-stent restenosis: 28.0% vs. 30.7%.
• Calcified lesions: 36.6% vs. 40.1% (P < .01).
• Renal disease: 17.4% vs. 19.5% (P < .01).

As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.

“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”

Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.

“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.

“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
 

Getting worse, not better

Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.

To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.

Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.

One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.

“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.

Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.

“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”

Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.

“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”

Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.

“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”

Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.

“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.

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

A real-world analysis reveals that women are consistently less likely to undergo intracoronary imaging as part of percutaneous coronary intervention (PCI), even though it benefits both sexes equally.

Results from nearly all PCIs performed in England and Wales between 2006 and 2019 showed the absolute rate of intracoronary imaging with either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was 5% lower in the later study years among women at 14.5%, compared with 19.6% in men (P < .001).

After adjustment, female sex was an independent predictor of lower intracoronary imaging use (odds ratio, 0.93; 95% confidence interval, 0.91-0.96), according to the study, published in JACC: Cardiovascular Interventions.

“One of the thoughts I had when we were running this analysis was, well, maybe the indications for that imaging, as recommended by guidelines, are less common in women,” Mamas Mamas, MD, told this news organization. “So what we did was to look at just cases where imaging is recommended by the EAPCI [European Association of Percutaneous Coronary Intervention].”

Again, the use of intracoronary imaging was consistently lower among women than among men for all of the following EAPCI-recommended indications:

• Acute coronary syndrome: 11.6% vs. 12.3% (P < .01).
• Stent thrombosis: 30.9% vs. 34.9% (P < .01).
• Long lesions: 13.1% vs. 16.3% (P < .01).
• Chronic total occlusions: 16.2% vs. 18.3% (P < .01).
• Left main stem PCI: 55.1% vs. 57.5% (P < .01).
• In-stent restenosis: 28.0% vs. 30.7%.
• Calcified lesions: 36.6% vs. 40.1% (P < .01).
• Renal disease: 17.4% vs. 19.5% (P < .01).

As to what might be driving the lower use, Dr. Mamas dismissed the argument that women undergo much simpler PCI, which wouldn’t benefit from imaging. Women do have smaller coronary arteries, however, and there is a belief that it’s easier to eyeball the size of vessels that are smaller rather than larger.

“I’m not convinced that’s entirely true,” he said. “I don’t have a good answer for you, I’m afraid. I don’t really know why we’re seeing it. I just think it’s one of those disparities that is important to highlight.”

Central to this belief is that the benefits of intracoronary imaging were found to be similar in men and women. Intracoronary imaging was associated with lower adjusted odds of in-hospital mortality (OR, 0.56; 95% CI, 0.48-0.64) and major adverse cardiac and cerebrovascular events (OR, 0.83; 95% CI, 0.76-0.91) in women and men (OR, 0.48; 95% CI, 0.44-0.53 and OR, 0.75; 95% CI, 0.71-0.80, respectively), compared with nonimaging groups.

“This really should be a call to arms, particularly given that we show this disparity persists, even in guideline-recommended cases where we should be using it,” said Dr. Mamas, from the Keele (England) Cardiovascular Research Group, Keele University, and Royal Stoke University Hospital, Stoke-on-Trent, England.

“Actually, I would argue that we should be using more imaging in women than men anyway because many of the presentations for acute coronary syndromes in women, like spontaneous coronary artery dissection or MINOCA [MI with nonobstructive coronary arteries], you often need intracoronary imaging to make that kind of diagnosis,” he observed.
 

Getting worse, not better

Previous studies have shown that women are less likely than men in acute coronary syndromes to receive the transradial approach and P2Y12 inhibitors, but none have specifically looked at intracoronary imaging, Dr. Mamas said.

To fill the gap, the researchers drew on data from 994,478 patients in the British Cardiovascular Intervention Society registry, of whom, 8.4% of 738,616 men and 7.9% of 255,862 women received intracoronary imaging.

Women in the imaging group were older, more likely to be an ethnic minority, and more likely to undergo PCI for non–ST-segment elevation MI than their male counterparts.

One of the more surprising findings was that rates of IVUS and OCT were superimposable between the sexes at the start of the study but quickly diverged starting in around 2012, when the technology took off, Dr. Mamas said. In the most recent data, use was about 3% lower in women overall and rising to 6% in those with stable angina.

“Whilst the disparities between men and women are significant, the bigger question is why are we using so little imaging in guideline-recommended cases where there is a benefit?” he said.

Possible actionable items, he suggested, include providing older physicians who didn’t have access to intracoronary imaging during their training with opportunities in their cath lab or with industry sponsors to increase their skills and confidence. Intracoronary imaging use could also be routinely captured in U.S. and European PCI registries and used as a quality metric.

“In left main, you see a massive difference between centers, and that’s the kind of data that drives discussion,” Dr. Mamas said. “If we start reporting quality metrics, such as radial use, intracoronary imaging, P2Y12 inhibitors by center, then you’ve got something to benchmark centers against.”

Nathaniel Smilowitz, MD, an interventional cardiologist at New York Langone Health, who was not associated with the study, said that it’s troubling to see that the utilization intravascular imaging is so low, despite randomized trials and large meta-analyses showing a mortality benefit associated with its use in PCI.

“Even among men, only 19.6% in the later years were getting intravascular imaging performed to guide their coronary intervention, so one out of five,” he said. “There are opportunities to improve.”

Dr. Smilowitz said he’s also perplexed as to why adoption would be lower in women but that the findings echo those in other domains where women receive less intensive cardiovascular therapy.

“There’s no biological, really plausible, mechanism as to why the need for intravascular imaging would be lower and, particularly, because they showed in stent thrombosis, for example, where intravascular imaging is tremendously important, there were still sex differences,” he said. “So even with clear indications for imaging, women just received the optimal therapy less often than men. It’s disappointing.”

Dr. Smilowitz agreed that there may be a need to incorporate intravascular imaging into metrics, which are reported back to physicians, potentially even for comparisons with peers or regional rates to incentivize physicians to improve uptake.

“As a society, we’ve been quite slow to integrate intravascular imaging to guide PCI and we can do better,” he said.

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

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

Non-Hispanic White children were more likely to receive diagnostic imaging at children’s hospitals’ emergency departments across the United States than were Hispanic children and non-Hispanic Black children, according to a large study published in JAMA Network Open.

Researchers found that, the more the percentage of children from minority groups cared for by a hospital increased, the wider the imaging gap between those children and non-Hispanic White children.

The cross-sectional study, led by Margaret E. Samuels-Kalow, MD, MPhil, MSHP, with the department of emergency medicine, Massachusetts General Hospital and Harvard Medical School in Boston, included 38 children’s hospitals and more than 12 million ED visits.

“These findings emphasize the urgent need for interventions at the hospital level to improve equity in imaging in pediatric emergency medicine,” the authors write.

Patients included in the study were younger than 18 and visited an ED from January 2016 through December 2019. Data were pulled from the Pediatric Health Information System.

Of the more than 12 million visits in this study, 3.5 million (28.7%) involved at least one diagnostic imaging test.

Diagnostic imaging was performed in 1.5 million visits (34.2%) for non-Hispanic White children; 790,961 (24.6%) for non-Hispanic Black children; and 907,222 (26.1%) for Hispanic children (P < .001).

Non-Hispanic Black children were consistently less likely to get diagnostic imaging than non-Hispanic White counterparts at every hospital in the study, no matter the imaging modality: radiography, ultrasonography, computed tomography, or magnetic resonance imaging.

Hispanic patients were generally less likely to get imaging than non-Hispanic White patients, though results were less consistent for ultrasound and MRI.

In a sensitivity analysis, when looking at imaging from patients’ first visit across the study cohort, non-Hispanic Black children were significantly less likely to get imaging than non-Hispanic White children (adjusted odds ratio, 0.77; 95% confidence interval, 0.74-0.79).

“This remained significant even after adjustment for a priori specified confounders including hospital propensity to image,” the authors write.

Authors acknowledge that it is possible that some of the differences may be attributable to the patient mix regarding severity of cases or indications for imaging by hospital, but they note that all models were adjusted for diagnosis-related group and other potential confounders.

This study did not assess whether one group is being overtested. Researchers also note that higher rates of imaging do not necessarily indicate higher quality of care.

However, the authors note, previous research has suggested overtesting of non-Hispanic White patients for head CT and chest pain, as well as patterns of overtreatment of non-Hispanic White patients who have bronchiolitis or viral upper respiratory tract infections.

Medell Briggs-Malonson, MD, MPH, chief of health equity, diversity and inclusion for the University of California, Los Angeles, Hospital and Clinic System, who was not part of the study, said in an interview “this all rings true.”

“This is not the first study we have had in either the pediatric or adult populations that shows disparate levels of care as well as health outcomes. Now we are starting to be able to measure it,” she said.

This study is further evidence of medical racism, she says, and highlights that it’s not the hospital choice or the insurance type affecting the numbers, she said.

“When you control for those factors, it looks to be it’s only due to race and that’s because of the very deep levels of implicit bias as well as explicit bias that we still have in our health systems and even in our providers,” said Dr. Briggs-Malonson, who is also an associate professor of emergency medicine at UCLA. “It’s incredibly important to identify and immediately address.”

What can be done?

Changing these patterns starts with knowing the numbers, the authors write.

“Hospitals should measure their own differences in imaging rates and increase awareness of existing areas of differential treatment as a starting point for improvement,” Dr. Samuels-Kalow and coauthors say.

Dr. Briggs-Malonson added that guidelines are very clear about when children should get imaging. Adhering to evidence-based guidelines can help avoid variations in care from external factors.

“If children are not receiving the absolute best comprehensive evaluation in the emergency department that they deserve, we can miss many different illnesses, which can lead to worse outcomes,” she noted.

As for what might motivate lack of imaging, Dr. Briggs-Malonson pointed to longstanding trends of providers thinking complaints raised by minority patients may not be as severe as they report. Conversely, in caring for White patients there may be a feeling that more tests and imaging may be better out of more fear of missing something, she said.

At UCLA, she says, dashboards have been developed to track statistics on care by age, race, ethnicity, language, insurance type, etc., though not specifically in pediatric imaging, to assess and address any care inequities.

Summer L. Kaplan, MD, MS, director of emergency radiology at Children’s Hospital of Philadelphia, who also was not part of the study, said the finding of racial disparities in pediatric ED imaging provides evidence that gaps still exist in providing the best care to all children and families seeking emergency care.

“However, it is important to recognize that more imaging does not equal better care,” she said. “More imaging may be associated with unnecessary, low-value tests that may add radiation and other risks but do not improve care.”

She said higher rates of imaging may occur when patients present early in the course of a disease, when the differential diagnosis remains broad.

If families have delayed seeking care because of time constraints, transportation problems, cost of care, or mistrust of the health system, children may present later in the course of a disease and require less imaging for a diagnosis, she explained.

“This paper offers a valuable look at the inequities that exist in pediatric emergency imaging use, and further research will be essential to understand and address the causes of these differences,” Dr. Kaplan said.

A coauthor reported compensation as a member of a Medical Review Committee for Highmark. Other coauthors reported grants from the U.S. Agency for Healthcare Research and Quality outside the submitted work. Dr. Briggs-Malonson and Dr. Kaplan reported no relevant financial relationships.

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Study 1 Overview (SCOT-HEART Investigators)

Objective: To assess cardiovascular mortality and nonfatal myocardial infarction at 5 years in patients with stable chest pain referred to cardiology clinic for management with either standard care plus computed tomography angiography (CTA) or standard care alone.

Design: Multicenter, randomized, open-label prospective study.

Setting and participants: A total of 4146 patients with stable chest pain were randomized to standard care or standard care plus CTA at 12 centers across Scotland and were followed for 5 years.

Main outcome measures: The primary end point was a composite of death from coronary heart disease or nonfatal myocardial infarction. Main secondary end points were nonfatal myocardial infarction, nonfatal stroke, and frequency of invasive coronary angiography (ICA) and coronary revascularization with percutaneous coronary intervention or coronary artery bypass grafting.

Main results: The primary outcome including the composite of cardiovascular death or nonfatal myocardial infarction was lower in the CTA group than in the standard-care group at 2.3% (48 of 2073 patients) vs 3.9% (81 of 2073 patients), respectively (hazard ratio, 0.59; 95% CI, 0.41-0.84; P = .004). Although there was a higher rate of ICA and coronary revascularization in the CTA group than in the standard-care group in the first few months of follow-up, the overall rates were similar at 5 years, with ICA performed in 491 patients and 502 patients in the CTA vs standard-care groups, respectively (hazard ratio, 1.00; 95% CI, 0.88-1.13). Similarly, coronary revascularization was performed in 279 patients in the CTA group and in 267 patients in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91-1.27). There were, however, more preventive therapies initiated in patients in the CTA group than in the standard-care group (odds ratio, 1.40; 95% CI, 1.19-1.65).

Conclusion: In patients with stable chest pain, the use of CTA in addition to standard care resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years; the main contributor to this outcome was a reduced nonfatal myocardial infarction rate. There was no difference in the rate of coronary angiography or coronary revascularization between the 2 groups at 5 years.

Study 2 Overview (DISCHARGE Trial Group)

Objective: To compare the effectiveness of computed tomography (CT) with ICA as a diagnostic tool in patients with stable chest pain and intermediate pretest probability of coronary artery disease (CAD).

Design: Multicenter, randomized, assessor-blinded pragmatic prospective study.

Setting and participants: A total of 3667 patients with stable chest pain and intermediate pretest probability of CAD were enrolled at 26 centers and randomized into CT or ICA groups. Only 3561 patients were included in the modified intention-to-treat analysis, with 1808 patients and 1753 patients in the CT and ICA groups, respectively.

Main outcome measures: The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke over 3.5 years. The main secondary outcomes were major procedure-related complications and patient-reported angina pectoris during the last 4 weeks of follow up.

Main results: The primary outcome occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 patients (3.0%) in the ICA group (hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). The secondary outcomes showed that major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 patients (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13-0.55). Rates of patient-reported angina in the final 4 weeks of follow-up were 8.8% in the CT group and 7.5% in the ICA group (odds ratio, 1.17; 95% CI, 0.92-1.48).

Conclusion: Risk of major adverse cardiovascular events from the primary outcome were similar in both the CT and ICA groups among patients with stable chest pain and intermediate pretest probability of CAD. Patients referred for CT had a lower rate of coronary angiography leading to fewer major procedure-related complications in these patients than in those referred for ICA.

Evaluation and treatment of obstructive atherosclerosis is an important part of clinical care in patients presenting with angina symptoms.¹ Thus, the initial investigation for patients with suspected obstructive CAD includes ruling out acute coronary syndrome and assessing quality of life.¹ The diagnostic test should be tailored to the pretest probability for the diagnosis of obstructive CAD.²

In the United States, stress testing traditionally has been used for the initial assessment in patients with suspected CAD,³ but recently CTA has been utilized more frequently for this purpose. Compared to a stress test, which often helps identify and assess ischemia, CTA can provide anatomical assessment, with higher sensitivity to identify CAD.⁴ Furthermore, it can distinguish nonobstructive plaques that can be challenging to identify with stress test alone.

Whether CTA is superior to stress testing as the initial assessment for CAD has been debated. The randomized PROMISE trial compared patients with stable angina who underwent functional stress testing or CTA as an initial strategy.⁵ They reported a similar outcome between the 2 groups at a median follow-up of 2 years. However, in the original SCOT-HEART trial (CT coronary angiography in patients with suspected angina due to coronary heart disease), which was published in the same year as the PROMISE trial, the patients who underwent initial assessment with CTA had a numerically lower composite end point of cardiac death and myocardial infarction at a median follow-up of 1.7 years (1.3% vs 2.0%, P = .053).⁶

Given this result, the SCOT-HEART investigators extended the follow-up to evaluate the composite end point of death from coronary heart disease or nonfatal myocardial infarction at 5 years.⁷ This trial enrolled patients who were initially referred to a cardiology clinic for evaluation of chest pain, and they were randomized to standard care plus CTA or standard care alone. At a median duration of 4.8 years, the primary outcome was lower in the CTA group (2.3%, 48 patients) than in the standard-care group (3.9%, 81 patients) (hazard ratio, 0.58; 95% CI, 0.41-0.84; P = .004). Both groups had similar rates of invasive coronary angiography and had similar coronary revascularization rates.

It is hypothesized that this lower rate of nonfatal myocardial infarction in patients with CTA plus standard care is associated with a higher rate of preventive therapies initiated in patients in the CTA-plus-standard-care group compared to standard care alone. However, the difference in the standard-care group should be noted when compared to the PROMISE trial. In the PROMISE trial, the comparator group had predominantly stress imaging (either nuclear stress test or echocardiography), while in the SCOT-HEART trial, the group had predominantly stress electrocardiogram (ECG), and only 10% of the patients underwent stress imaging. It is possible the difference seen in the rate of nonfatal myocardial infarction was due to suboptimal diagnosis of CAD with stress ECG, which has lower sensitivity compared to stress imaging.

The DISCHARGE trial investigated the effectiveness of CTA vs ICA as the initial diagnostic test in the management of patients with stable chest pain and an intermediate pretest probability of obstructive CAD.⁸ At 3.5 years of follow-up, the primary composite of cardiovascular death, myocardial infarction, or stroke was similar in both groups (2.1% vs 3.0; hazard ratio, 0.70; 95% CI, 0.46-1.07; P = .10). Importantly, as fewer patients underwent ICA, the risk of procedure-related complication was lower in the CTA group than in the ICA group. However, it is important to note that only 25% of the patients diagnosed with obstructive CAD had greater than 50% vessel stenosis, which raises the question of whether an initial invasive strategy is appropriate for this population.

The strengths of these 2 studies include the large number of patients enrolled along with adequate follow-up, 5 years in the SCOT-HEART trial and 3.5 years in the DISCHARGE trial. The 2 studies overall suggest the usefulness of CTA for assessment of CAD. However, the control groups were very different in these 2 trials. In the SCOT-HEART study, the comparator group was primarily assessed by stress ECG, while in the DISCHARGE study, the comparator group was primary assessed by ICA. In the PROMISE trial, the composite end point of death, myocardial infarction, hospitalization for unstable angina, or major procedural complication was similar when the strategy of initial CTA was compared to functional testing with imaging (exercise ECG, nuclear stress testing, or echocardiography).⁵ Thus, clinical assessment is still needed when clinicians are selecting the appropriate diagnostic test for patients with suspected CAD. The most recent guidelines give similar recommendations for CTA compared to stress imaging.⁹ Whether further improvement in CTA acquisition or the addition of CT fractional flow reserve can further improve outcomes requires additional study.

Applications for Clinical Practice and System Implementation

In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful in diagnosis compared to stress ECG and in reducing utilization of low-yield ICA. Whether CTA is more useful compared to the other noninvasive stress imaging modalities in this population requires further study.

Practice Points

• In patients with stable chest pain and intermediate pretest probability of CAD, CTA is useful compared to stress ECG.
• Use of CTA can potentially reduce the use of low-yield coronary angiography.

–Thai Nguyen, MD, Albert Chan, MD, Taishi Hirai, MD
University of Missouri, Columbia, MO

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

Sparring among professional mixed martial arts (MMA) practitioners may have both positive and negative effects on the brain, early research suggests.

Investigators found sparring, defined as strategically hitting opponents with kicks, punches, and other strikes during practice sessions, is linked to increased white matter hyperintensities in the brain, pointing to possible vascular damage from repeated head trauma. However, the study results also show sparring was associated with a larger bilateral caudate which, in theory, is neuroprotective.

“From our preliminary study, sparring practice in MMA fighters may have a ‘double-edged sword’ effect on the brain,” study investigator Aaron Esagoff, a second-year medical student at Johns Hopkins University School of Medicine, Baltimore, told this news organization.

Growing popularity

MMA is a full-contact combat sport that has become increasingly popular over the past 15 years. It combines techniques from boxing, wrestling, karate, judo, and jujitsu.

To prepare for fights, MMA practitioners incorporate sparring and grappling, which use techniques such as chokes and locks to submit an opponent. Head protection is sometimes incorporated during practice, but is not the norm during a fight, said Mr. Esagoff.

The study investigated sparring during practice rather than fights because, he said, MMA competitors only fight a few times a year but spend hundreds of hours training. “So the health effects of training are going to be really important,” he said.

As with other combat sports, MMA involves hits to the head. Previous research has shown repetitive head trauma can lead to neurodegenerative diseases, including chronic traumatic encephalopathy (CTE) and Alzheimer’s disease, Mr. Esagoff noted.

Previous studies have also linked more professional fights and years of fighting to a decrease in brain volume among MMA fighters, he added.

The new analysis was conducted as part of the Professional Fighters Brain Health Study, a longitudinal cohort study of MMA professional fighters. It included 92 fighters with data available on MRI and habits regarding practicing. The mean age of the participants was 30 years, 62% were White, and 85% were men.

The study examined sparring but did not include grappling because of “several challenges” with the current data analysis, Mr. Esagoff said. Researchers adjusted for age, sex, education, race, number of fights, total intracranial volume, and type of MRI scanner used.
 

A ‘highly strategic’ sport

Results showed a strong association between the number of sparring rounds per week and increased white matter hyperintensity volume (mcL) on MRI (P = .039).

This suggests white matter damage, possibly a result of direct neuronal injury, vascular damage, or immune modulation, said Mr. Esagoff. However, another mechanism may be involved, he added.

There was also a significant association between sparring and increased size of the caudate nucleus, an area of the brain involved in movement, learning, and memory (P = .014 for right caudate volume, P = .012 for left caudate volume).

There are some theories that might explain this finding, said Mr. Esagoff. For example, individuals who spar more may get better at avoiding impacts and injuries during a fight, which might in turn affect the size of the caudate.

The controlled movements and techniques used during sparring could also affect the caudate. “Some research has shown that behavior, learning, and/or exercise may increase the size of certain brain regions,” Mr. Esagoff said.

He noted the “highly strategic” nature of combat sports – and used the example of Brazilian jiu-jitsu. That sport “is known as human chess because it takes a thoughtful approach to defeat a larger opponent with base, leverage, and technique,” he said.

However, Mr. Esagoff stressed that while it is possible movements involved in MMA increase caudate size, this is just a theory at this point.

A study limitation was that fighters volunteered to participate and may not represent all fighters. As well, the study was cross-sectional and looked at only one point in time, so it cannot infer causation.

Overall, the new findings should help inform fighters, governing bodies, and the public about the potential risks and benefits of different styles of MMA fighting and practice, although more research is needed, said Mr. Esagoff.

He and his team now plan to conduct a longer-term study and investigate effects of grappling on brain structure and function in addition to sparring.
 

Jury still out

Commenting on the study, Howard Liu, MD, chair of the University of Nebraska Medical Center department of psychiatry and incoming chair of the APA’s Council on Communications, said the jury “is clearly still out” when it comes to the investigation of brain impacts.

“We don’t know quite what these changes fully correlate to,” said Dr. Liu, who moderated a press briefing highlighting the study.

He underlined the importance of protecting athletes vulnerable to head trauma, be they professionals or those involved at the youth sports level.

Dr. Liu also noted the “extreme popularity” and rapid growth of MMA around the world, which he said provides an opportunity for researchers to study these professional fighters.

“This is a unique population that signed up in the midst of hundreds of hours of sparring to advance neuroscience, and that’s quite amazing,” he said.

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

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

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

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

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

The first international survey of parental benefits and policies among cardiovascular training programs shows wide variability among institutions.

Although a majority of cardiology fellows became parents during training, the survey found that family benefits and policies were not uniformly available and that knowledge about the existence of such policies was low across all institutions.

The findings are published in the Journal of the American College of Cardiology.

Such variability highlights disparities in real-world experiences, say Estefania Oliveros, MD, Temple University Hospital, Philadelphia, and colleagues.

“There are no policies to protect cardiology trainees when they become parents that are uniform across the United States or even internationally, even though, according to our survey, 61.7% become parents during training,” Dr. Oliveros told this news organization.

Dr. Oliveros said she wanted to learn more about the status of institutional practices surrounding pregnant trainees during cardiovascular fellowship, not only in the U.S., but internationally: “I wanted to study this because of my own experience.”

“I was probably the first pregnant trainee at my institution, and there were no specific policies in place, so I had to find out on my own what to do about radiation safety, where I would breastfeed, schedule changes, how that would impact my graduation time, things like that,” Dr. Oliveros said. “It would be nice if you had the resources and your institution could accommodate your needs, instead of every time you have a pregnant person on your staff, you have to reinvent the wheel.”

Dr. Oliveros and colleagues conducted an online survey during August 2020-October 2020 that was distributed via social media. Responses were made anonymous to encourage unbiased feedback.

Among the 417 completed responses, 47 (11.3%) were from training program directors, 146 (35%) from current or former pregnant trainees, and 224 (53.7%) from current or former trainees who were not pregnant during cardiology training. Two-thirds of the respondents (67.1%) were parents.

Most survey respondents said they became pregnant during the third year of general cardiology (29.1%), followed by the first year of general cardiology (26.3%), and the second year of general cardiology (23.5%).

Only 13 of the 47 training program directors (27.7%) received guidance or training on how to accommodate pregnant trainees during fellowship.

Additionally, 26% of the trainees reported their institution had readily available breastfeeding and pumping policies, 39% responded that their institution had no such policies, and 34.9% said they did not know.

Nearly one-half of the programs offered rearrangement of schedules because of radiation concerns, 27.5% did not.

The amount of parental leave varied greatly worldwide. For Europe, Central and South America, Africa, and Australia, the average parental leave was more than 4 months; for Canada, it was more than 3 months; for the United States, it was 1 to 2 months; and for Asia, it was 3 to 4 weeks.

“There is no uniformity, no policies for things like breastfeeding or places where you can pump. None of that is installed, even though by law we’re supposed to have these things,” Dr. Oliveros said.

In all countries, paternity leave was uncommon (2.6% of respondents), even though 48.5% of the programs had paternity leave.

“I would like to see associations, program directors, even trainees helping each other in finding ways to accommodate parents to promote wellness and assure that trainees can have both good training and life balance,” she added.

In an accompanying editorial, Ileana L. Piña, MD, MPH, Thomas Jefferson Institute, Philadelphia, writes: “Enough has been said about our need for a greater percentage of women cardiologists. There is no need to further debate that fact. However, it is puzzling that despite > 50% of medical students being women, the cardiology specialty is fraught with recent survey reports of hostility in the workplace, concerns of long hours, exposure to radiation, and poor work-life balance that can compel trainees to choose delaying pregnancy or taking unpaid leave, which will, in turn, delay training. Therefore, it is not surprising that only 14.9% of cardiologist specialists and 21.9% of cardiology fellows are women.”

Dr. Piña notes that while the authors understand that it’s difficult to change national policies, they issue a “call to action” for organizations and program directors to demonstrate leadership by developing fair and balanced decisions regarding parental policies.

“Those decisions are so impactful that they can change career trajectories for the better or worse ... the current status is unacceptable and must change for the benefit of all trainees, their families, and the program directors. The problem is too important and pervasive,” she adds.

Dr. Piña concludes: “Perhaps if the women who are the subjects of, and often the unwitting party to, administrative decisions about their lives, choices, and welfare were invited to contribute to the changes, we would finally see an increase in the number of women in cardiology careers. After all, aren’t we about diversity and belonging?”

“We need to normalize pregnancy and parental leave across the globe,” Laxmi S. Mehta, MD, Ohio State University Weiner Medical Center, Columbus, said in an interview.

As previously reported, Dr. Mehta recently led a study that surveyed 323 women cardiologists who were working while they were pregnant. Her study found that 75% of these women experienced discriminatory maternity leave practices, some of which were likely violations of the federal Family and Medical Leave Act.

“If we want more women to pursue a career in cardiology, then employers and health systems need to adequately support parenthood, including allowing people to spend uninterrupted time with their newborns without the fear of discrimination, retaliation, or financial burden,” Dr. Mehta said.

Limitations of the study are the small sample size, potential for bias associated with social media distribution, and the fact that 75% of respondents were women, Dr. Oliveros and colleagues write.

Dr. Oliveros, Dr. Piña, and Dr. Mehta report no relevant financial relationships.

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

For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).

Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.

“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.

University of British Columbia

Mechanistic insights

Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.

In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.

They found that stimulating the dorsolateral prefrontal cortex led to “widespread, acute, and transient” changes in functional connectivity, particularly in brain regions involved in multiple function – from managing emotional responses to memory and motor control.

Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.

The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.

“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.

“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.

With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
 

New generation of tms researchers

Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”

What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.

He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.

“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.

Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.

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

For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).

Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.

“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.

University of British Columbia

Mechanistic insights

Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.

In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.

They found that stimulating the dorsolateral prefrontal cortex led to “widespread, acute, and transient” changes in functional connectivity, particularly in brain regions involved in multiple function – from managing emotional responses to memory and motor control.

Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.

The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.

“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.

“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.

With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
 

New generation of tms researchers

Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”

What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.

He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.

“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.

Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.

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

For the first time, researchers understand what happens to the brain when patients with treatment-resistant depression receive repetitive transcranial magnetic stimulation (rTMS).

Using functional magnetic resonance imaging (fMRI), they showed that rTMS induces widespread alterations in functional connectivity in brain regions involved in emotion and motor control.

“‘How does rTMS work?’ is one of the most frequent questions I get in clinic. Providing an accurate explanation and narrative to patients is critical,” senior investigator Fidel Vila-Rodriguez, MD, PhD, director of the Non-Invasive Neurostimulation Therapies Laboratory, University of British Columbia, Vancouver, told this news organization.

University of British Columbia

Mechanistic insights

Although rTMS has proven efficacy for treatment-resistant depression, the mechanisms behind how it affects the brain are not well understood.

In the current study, researchers used fMRI to assess changes in functional connectivity induced by a single rTMS session in 26 women and 12 men with treatment-resistant depression.

They found that stimulating the dorsolateral prefrontal cortex led to “widespread, acute, and transient” changes in functional connectivity, particularly in brain regions involved in multiple function – from managing emotional responses to memory and motor control.

Following a 4-week course of rTMS, these connectivity changes predicted about 30% of the variance of improvement in scores on the Montgomery-Åsberg Depression Rating Scale after rTMS treatment.

The most robust predictive associations involved connections between prefrontal regions and motor, parietal, and insular cortices and between bilateral regions of the thalamus.

“By demonstrating this principle and identifying regions of the brain that are activated by rTMS, we can now try to understand whether this pattern can be used as a biomarker,” Dr. Vila-Rodriguez said in a news release.

“This work provides a mechanistic explanation of what rTMS does to treat depression and supports the notion that for rTMS to treat depressive symptoms a distributed change in brain activity (network or circuit base) is necessary,” he told this news organization.

With funding from the Canadian Institutes of Health Research (CIHR), the team will next see if they can use fMRI to guide rTMS at the individual level, with the ultimate goal of “personalizing” rTMS using individualized functional targets, Dr. Vila-Rodriguez said.
 

New generation of tms researchers

Reached for comment, Jonathan Downar, MD, PhD, department of psychiatry, University of Toronto, noted that TMS can be “very effective” for treatment-resistant depression, and it has a “very clean side effect profile compared to medications.”

What the field is trying to figure out now is “who it works for and how we can predict more effectively who’s going to benefit from it,” Dr. Downar said in an interview.

He noted that the study’s investigators are part of a “new generation of TMS researchers who are bringing new ideas into the fold and figuring out how to use brain imaging to personalize the treatment.” This study represents “a step” in that direction.

“A challenge for the field is that it’s often pretty easy to demonstrate a change at the group level, but the question is whether we can use that at the individual level. That’s a higher bar to meet, and we’re still not there yet,” Dr. Downar added.

Support for the study was provided by Brain Canada, the Michael Smith Foundation for Health Research and the Vancouver Coastal Health Research Institute. Dr. Vila-Rodriguez has received research support from CIHR, Brain Canada, the Michael Smith Foundation for Health Research, the Vancouver Coastal Health Research Institute, and the Weston Brain Institute for investigator-initiated research and philanthropic support from the Seedlings Foundation; he received in-kind equipment support from MagVenture for this investigator-initiated trial; and he has received honoraria for participation on an advisory board for Janssen. Dr. Downar has served as an adviser for BrainCheck, NeuroStim TMS, and Salience Neuro Health; received research grant from CIHR, National Institute for Mental Health, Brain Canada, Canadian Biomarker Integration Network in Depression, Ontario Brain Institute, Klarman Family Foundation, Arrell Family Foundation and the Edgestone Foundation; received travel stipends from Lundbeck and ANT Neuro; and received in-kind equipment support for investigator-initiated trials from MagVenture.

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

A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.

As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.

The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.

Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.

In addition, the Supplemental tables list the following:

• 659 patients in Duke group 5, not 894 as in the paper.
• 894 patients in Duke group 4, not 743 as in the paper.
• 743 patients in Duke group 3, not 179 as in the paper.

The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.

“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”

Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.

Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.

Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.

A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.

The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.

They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.

Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”

She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.

“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.

She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”

Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.

As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
 

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

A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.

As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.

The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.

Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.

In addition, the Supplemental tables list the following:

• 659 patients in Duke group 5, not 894 as in the paper.
• 894 patients in Duke group 4, not 743 as in the paper.
• 743 patients in Duke group 3, not 179 as in the paper.

The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.

“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”

Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.

Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.

Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.

A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.

The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.

They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.

Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”

She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.

“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.

She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”

Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.

As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
 

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

A recent ISCHEMIA trial substudy is under scrutiny from surgeons for a data discrepancy, rekindling concerns about reliance on the landmark trial data in the latest coronary revascularization guidelines.

As previously reported, the main ISCHEMIA findings showed no significant benefit for an initial strategy of percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG) over medical therapy in patients with stable moderate to severe ischemic heart disease.

The 2021 substudy by Reynolds et al. showed that coronary artery disease (CAD) severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the trial, whereas ischemia severity did not.

Cardiac surgeons Joseph F. Sabik III, MD, and Faisal Bakaeen, MD, however, spotted that only 40 patients are in the Duke category 6 group (three-vessel severe stenosis of at least 70% or two-vessel severe stenosis with a proximal left anterior descending lesion) in Supplemental tables 1 and 2, whereas 659 are in the main paper.

In addition, the Supplemental tables list the following:

• 659 patients in Duke group 5, not 894 as in the paper.
• 894 patients in Duke group 4, not 743 as in the paper.
• 743 patients in Duke group 3, not 179 as in the paper.

The surgeons penned a letter to Circulation early in April flagging the discrepancies, but say it was rejected April 15 because it was submitted outside the journal’s 6-week window for letters. They posted a public comment on the Remarq research platform, as advised by Circulation’s editorial office, and reached out directly to the authors and ISCHEMIA leadership.

“They just keep saying it’s a simple formatting error. Well, if it is a simple formatting error, then fix it,” Dr. Sabik, chair of surgery at University Hospitals Cleveland Medical Center, said in an interview. “But here we are now, a month later, and they still haven’t published our letter. Why? We’re the ones who identified the problem.”

Dr. Sabik said the accuracy of the data has important implications because the recent AHA/ACC/SCAI coronary revascularization guidelines used the ISCHEMIA data to downgrade the CABG recommendation for complex multivessel disease from class 1 to class 2B. Patients with a Duke 6 score are also typically the ones referred for CABG by today’s heart teams.

Several surgical societies have contested the guidelines, questioning whether the ISCHEMIA patients are truly reflective of those seen in clinical practice and questioning the decision to treat PCI and surgery as equivalent strategies to decrease ischemic events.

Dr. Bakaeen, from the Cleveland Clinic, told this news organization they don’t want a public battle over the data like the one that befell the EXCEL trial, and that it’s entirely possible the investigators might have inadvertently upgraded all the Duke score assignments by 1.

A systematic error, however, is more plausible than a formatting error, he said, because Supplemental tables 1 and 2 correspond exactly to the Duke 1 to Duke 7 sequence, suggesting the tables are correct and that the error might have occurred downstream, including in the manuscript.

The numbers should be consistent across all the ISCHEMIA manuscripts, Dr. Bakaeen added, but currently “don’t add up,” even after adjustment for different denominators, and especially for participants with left main disease.

They hope that publication of their letter, he said, will convince the authors to publicly share the data for patients in each of the seven modified Duke categories.

Lead author of the ISCHEMIA substudy, Harmony Reynolds, MD, New York (N.Y.) University Langone Health, told this news organization via email that as a result of a “formatting error in the transfer of data from the statistical output file to a Word document, data in Supplemental tables 1 and 2 were incorrect.”

She explained that they planned to present six, not seven, rows for the Duke score in the tables, collapsing the first two categories of nonobstructive disease (Duke 1-2), as they were in all other tables and figures. However, the Supplemental tables had incorrect row headings and because the Word program is designed to fill all available rows, it inserted the data from the output file into a seven-row table shell, duplicating the values for row 1 in the last row for left main disease of at least 50%.

“The data were correctly presented in the main manuscript tables and figures and in the remainder of the supplement, with a total of 659 patients in the subset with modified Duke prognostic index category 6 on coronary CT angiography,” Dr. Reynolds said.

She noted that Circulation will issue a correction. In addition, “we are in the process of preparing the data for public sharing soon. The data will include the Duke prognostic score at all levels.”

Circulation editor-in-chief Joseph A. Hill, MD, PhD, chief of cardiology at UT Southwestern Medical Center, Dallas, declined to be interviewed but confirmed via email that Dr. Bakaeen and Dr. Sabik’s letter and the correction will be published the week of May 16.

As for the delay, he said, “I received their reach-out just over 1 week ago, and per protocol, we conducted an internal evaluation of their allegations, which took a bit of time.”
 

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

Knee and shoulder pain are common complaints for patients in the primary care office.

But identifying the source of the pain can be complicated,

and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.

Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.

The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”

The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.

“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”

Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”

Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.

“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.

Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.

Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.

An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.

An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.

Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”

In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.

Treating knee pain

Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.

Three types of injections also can help:

• Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
• Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
• Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).

The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.  

“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”

He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.

Shoulder pain

The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.

As with knee pain, the same assessment routine largely applies.

First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?

Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.

Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.

As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.

MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.

Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.

Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.

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

Deaths from COVID-19 may have caught more attention lately, but heart disease remains the leading cause of death in the United States.

More than 300,000 Americans will die this year of sudden cardiac arrest (also called sudden cardiac death, or SCD), when the heart abruptly stops working.

These events happen suddenly and often without warning, making them nearly impossible to predict. But that may be changing, thanks to 3D imaging and artificial intelligence (AI) technology under study at Johns Hopkins University, Baltimore.

Svisio/Thinkstock

There, researchers are working to create more accurate and personalized models of the heart – and not just any heart, your heart, if you have heart disease.

“Right now, a clinician can only say whether a patient is at risk or not at risk for sudden death,” says Dan Popescu, PhD, a Johns Hopkins research scientist and first author of a new study on AI’s ability to predict sudden cardiac arrest. “With this new technology, you can have much more nuanced predictions of probability of an event over time.”

Put another way: With AI, clinicians may be able not only to predict if someone is at risk for sudden cardiac arrest, but also when it is most likely to happen. They can do this using a much clearer and more personalized look at the electrical “wiring” of your heart.
 

Your heart, the conductor

Your heart isn’t just a metronome responsible for keeping a steady stream of blood pumping to tissues with every beat. It’s also a conductor through which vital energy flows.

To make the heart beat, electrical impulses flow from the top to the bottom of the organ. Healthy heart cells relay this electricity seamlessly. But in a heart damaged by inflammation or a past heart attack, scar tissue will block the energy flow.

When an electrical impulse encounters a scarred area, the signal can become erratic, disrupting the set top-to-bottom path and causing irregular heartbeats (arrhythmias), which increase someone’s danger of sudden cardiac death.
 

Seeing the heart in 3D

Today’s tests offer some insights into the heart’s makeup. For example, MRI scans can reveal damaged areas. PET scans can show inflammation. And EKGs can record the heart’s electrical signals from beat to beat.

But all these technologies offer only a snapshot, showing heart health at a moment in time. They can’t predict the future. That’s why scientists at Johns Hopkins are going further to develop 3D digital replicas of a person’s heart, known as computational heart models.

Computational models are computer-simulated replicas that combine mathematics, physics, and computer science. These models have been around for a long time and are used in many fields, ranging from manufacturing to economics.

In heart medicine, these models are populated with digital “cells,” which imitate living cells and can be programmed with different electrical properties, depending on whether they are healthy or diseased.

“Currently available imaging and testing (MRIs, PETs, EKGs) give some representation of the scarring, but you cannot translate that to what is going to happen over time,” says Natalia Trayanova, PhD, of the Johns Hopkins department of biomedical engineering.

“With computational heart models, we create a dynamic digital image of the heart. We can then give the digital image an electrical stimulus and assess how the heart is able to respond. Then you can better predict what is going to happen.”

The computerized 3D models also mean better, more accurate treatment for heart conditions.

For example, a common treatment for a type of arrhythmia known as atrial fibrillation is ablation, or burning some heart tissue. Ablation stops the erratic electrical impulses causing the arrhythmia, but it can also damage otherwise healthy heart cells.

A personalized computational heart model could allow doctors to see more accurately what areas should and shouldn’t be treated for a specific patient.
 

Using deep learning AI to predict health outcomes

Dr. Trayanova’s colleague Dr. Popescu is applying deep learning and AI to do more with computerized heart models to predict the future.

In a recent paper in Nature Cardiovascular Research, the research team showed their algorithm assessed the health of 269 patients and was able to predict the chance of sudden cardiac arrest up to 10 years in advance.

“This is really the first time ever, as far as we know, where deep learning technology has been proven to analyze scarring of the heart in a successful way,” Dr. Popescu says.

Dr. Popescu and Dr. Trayanova say the AI algorithm gathers information from the 3D computational heart models with patient data like MRIs, ethnicity, age, lifestyle, and other clinical information. Analyzing all these data can produce accurate and consistent estimates about how long patients might live if they are at risk for sudden death.

“You can’t afford to be wrong. If you are wrong, you can actually impact a patient’s quality of life dramatically,” Dr. Popescu says. “Having clinicians use this technology in the decision-making process will provide confidence in a better diagnosis and prognosis.”

While the current study was specifically about patients with a particular type of heart disease, Dr. Popescu says his algorithm can also be trained to assess other health conditions.

So when might you see this being used outside of a research study? Dr. Trayanova predicts 3D imaging of heart models could be available in 2 years, but first the technique must be tested in more clinical trials – some of which are happening right now.

Adding AI to the heart models will require more studies and Food and Drug Administration approval, so the timeline is less clear. But perhaps the biggest hurdle is that after approval the technologies would need to be adopted and used by clinicians and caregivers.

“The much harder question to answer is, ‘When will doctors be perfectly comfortable with AI tools?’ And I don’t know the answer,” Dr. Popescu says. “How to use AI as an aid in the decision-making process is something that’s not currently taught.”

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

Deaths from COVID-19 may have caught more attention lately, but heart disease remains the leading cause of death in the United States.

More than 300,000 Americans will die this year of sudden cardiac arrest (also called sudden cardiac death, or SCD), when the heart abruptly stops working.

These events happen suddenly and often without warning, making them nearly impossible to predict. But that may be changing, thanks to 3D imaging and artificial intelligence (AI) technology under study at Johns Hopkins University, Baltimore.

Svisio/Thinkstock

There, researchers are working to create more accurate and personalized models of the heart – and not just any heart, your heart, if you have heart disease.

“Right now, a clinician can only say whether a patient is at risk or not at risk for sudden death,” says Dan Popescu, PhD, a Johns Hopkins research scientist and first author of a new study on AI’s ability to predict sudden cardiac arrest. “With this new technology, you can have much more nuanced predictions of probability of an event over time.”

Put another way: With AI, clinicians may be able not only to predict if someone is at risk for sudden cardiac arrest, but also when it is most likely to happen. They can do this using a much clearer and more personalized look at the electrical “wiring” of your heart.
 

Your heart, the conductor

Your heart isn’t just a metronome responsible for keeping a steady stream of blood pumping to tissues with every beat. It’s also a conductor through which vital energy flows.

To make the heart beat, electrical impulses flow from the top to the bottom of the organ. Healthy heart cells relay this electricity seamlessly. But in a heart damaged by inflammation or a past heart attack, scar tissue will block the energy flow.

When an electrical impulse encounters a scarred area, the signal can become erratic, disrupting the set top-to-bottom path and causing irregular heartbeats (arrhythmias), which increase someone’s danger of sudden cardiac death.
 

Seeing the heart in 3D

Today’s tests offer some insights into the heart’s makeup. For example, MRI scans can reveal damaged areas. PET scans can show inflammation. And EKGs can record the heart’s electrical signals from beat to beat.

But all these technologies offer only a snapshot, showing heart health at a moment in time. They can’t predict the future. That’s why scientists at Johns Hopkins are going further to develop 3D digital replicas of a person’s heart, known as computational heart models.

Computational models are computer-simulated replicas that combine mathematics, physics, and computer science. These models have been around for a long time and are used in many fields, ranging from manufacturing to economics.

In heart medicine, these models are populated with digital “cells,” which imitate living cells and can be programmed with different electrical properties, depending on whether they are healthy or diseased.

“Currently available imaging and testing (MRIs, PETs, EKGs) give some representation of the scarring, but you cannot translate that to what is going to happen over time,” says Natalia Trayanova, PhD, of the Johns Hopkins department of biomedical engineering.

“With computational heart models, we create a dynamic digital image of the heart. We can then give the digital image an electrical stimulus and assess how the heart is able to respond. Then you can better predict what is going to happen.”

The computerized 3D models also mean better, more accurate treatment for heart conditions.

For example, a common treatment for a type of arrhythmia known as atrial fibrillation is ablation, or burning some heart tissue. Ablation stops the erratic electrical impulses causing the arrhythmia, but it can also damage otherwise healthy heart cells.

A personalized computational heart model could allow doctors to see more accurately what areas should and shouldn’t be treated for a specific patient.
 

Using deep learning AI to predict health outcomes

Dr. Trayanova’s colleague Dr. Popescu is applying deep learning and AI to do more with computerized heart models to predict the future.

In a recent paper in Nature Cardiovascular Research, the research team showed their algorithm assessed the health of 269 patients and was able to predict the chance of sudden cardiac arrest up to 10 years in advance.

“This is really the first time ever, as far as we know, where deep learning technology has been proven to analyze scarring of the heart in a successful way,” Dr. Popescu says.

Dr. Popescu and Dr. Trayanova say the AI algorithm gathers information from the 3D computational heart models with patient data like MRIs, ethnicity, age, lifestyle, and other clinical information. Analyzing all these data can produce accurate and consistent estimates about how long patients might live if they are at risk for sudden death.

“You can’t afford to be wrong. If you are wrong, you can actually impact a patient’s quality of life dramatically,” Dr. Popescu says. “Having clinicians use this technology in the decision-making process will provide confidence in a better diagnosis and prognosis.”

While the current study was specifically about patients with a particular type of heart disease, Dr. Popescu says his algorithm can also be trained to assess other health conditions.

So when might you see this being used outside of a research study? Dr. Trayanova predicts 3D imaging of heart models could be available in 2 years, but first the technique must be tested in more clinical trials – some of which are happening right now.

Adding AI to the heart models will require more studies and Food and Drug Administration approval, so the timeline is less clear. But perhaps the biggest hurdle is that after approval the technologies would need to be adopted and used by clinicians and caregivers.

“The much harder question to answer is, ‘When will doctors be perfectly comfortable with AI tools?’ And I don’t know the answer,” Dr. Popescu says. “How to use AI as an aid in the decision-making process is something that’s not currently taught.”

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

Deaths from COVID-19 may have caught more attention lately, but heart disease remains the leading cause of death in the United States.

More than 300,000 Americans will die this year of sudden cardiac arrest (also called sudden cardiac death, or SCD), when the heart abruptly stops working.

These events happen suddenly and often without warning, making them nearly impossible to predict. But that may be changing, thanks to 3D imaging and artificial intelligence (AI) technology under study at Johns Hopkins University, Baltimore.

Svisio/Thinkstock

There, researchers are working to create more accurate and personalized models of the heart – and not just any heart, your heart, if you have heart disease.

“Right now, a clinician can only say whether a patient is at risk or not at risk for sudden death,” says Dan Popescu, PhD, a Johns Hopkins research scientist and first author of a new study on AI’s ability to predict sudden cardiac arrest. “With this new technology, you can have much more nuanced predictions of probability of an event over time.”

Put another way: With AI, clinicians may be able not only to predict if someone is at risk for sudden cardiac arrest, but also when it is most likely to happen. They can do this using a much clearer and more personalized look at the electrical “wiring” of your heart.
 

Your heart, the conductor

Your heart isn’t just a metronome responsible for keeping a steady stream of blood pumping to tissues with every beat. It’s also a conductor through which vital energy flows.

To make the heart beat, electrical impulses flow from the top to the bottom of the organ. Healthy heart cells relay this electricity seamlessly. But in a heart damaged by inflammation or a past heart attack, scar tissue will block the energy flow.

When an electrical impulse encounters a scarred area, the signal can become erratic, disrupting the set top-to-bottom path and causing irregular heartbeats (arrhythmias), which increase someone’s danger of sudden cardiac death.
 

Seeing the heart in 3D

Today’s tests offer some insights into the heart’s makeup. For example, MRI scans can reveal damaged areas. PET scans can show inflammation. And EKGs can record the heart’s electrical signals from beat to beat.

But all these technologies offer only a snapshot, showing heart health at a moment in time. They can’t predict the future. That’s why scientists at Johns Hopkins are going further to develop 3D digital replicas of a person’s heart, known as computational heart models.

Computational models are computer-simulated replicas that combine mathematics, physics, and computer science. These models have been around for a long time and are used in many fields, ranging from manufacturing to economics.

In heart medicine, these models are populated with digital “cells,” which imitate living cells and can be programmed with different electrical properties, depending on whether they are healthy or diseased.

“Currently available imaging and testing (MRIs, PETs, EKGs) give some representation of the scarring, but you cannot translate that to what is going to happen over time,” says Natalia Trayanova, PhD, of the Johns Hopkins department of biomedical engineering.

“With computational heart models, we create a dynamic digital image of the heart. We can then give the digital image an electrical stimulus and assess how the heart is able to respond. Then you can better predict what is going to happen.”

The computerized 3D models also mean better, more accurate treatment for heart conditions.

For example, a common treatment for a type of arrhythmia known as atrial fibrillation is ablation, or burning some heart tissue. Ablation stops the erratic electrical impulses causing the arrhythmia, but it can also damage otherwise healthy heart cells.

A personalized computational heart model could allow doctors to see more accurately what areas should and shouldn’t be treated for a specific patient.
 

Using deep learning AI to predict health outcomes

Dr. Trayanova’s colleague Dr. Popescu is applying deep learning and AI to do more with computerized heart models to predict the future.

In a recent paper in Nature Cardiovascular Research, the research team showed their algorithm assessed the health of 269 patients and was able to predict the chance of sudden cardiac arrest up to 10 years in advance.

“This is really the first time ever, as far as we know, where deep learning technology has been proven to analyze scarring of the heart in a successful way,” Dr. Popescu says.

Dr. Popescu and Dr. Trayanova say the AI algorithm gathers information from the 3D computational heart models with patient data like MRIs, ethnicity, age, lifestyle, and other clinical information. Analyzing all these data can produce accurate and consistent estimates about how long patients might live if they are at risk for sudden death.

“You can’t afford to be wrong. If you are wrong, you can actually impact a patient’s quality of life dramatically,” Dr. Popescu says. “Having clinicians use this technology in the decision-making process will provide confidence in a better diagnosis and prognosis.”

While the current study was specifically about patients with a particular type of heart disease, Dr. Popescu says his algorithm can also be trained to assess other health conditions.

So when might you see this being used outside of a research study? Dr. Trayanova predicts 3D imaging of heart models could be available in 2 years, but first the technique must be tested in more clinical trials – some of which are happening right now.

Adding AI to the heart models will require more studies and Food and Drug Administration approval, so the timeline is less clear. But perhaps the biggest hurdle is that after approval the technologies would need to be adopted and used by clinicians and caregivers.

“The much harder question to answer is, ‘When will doctors be perfectly comfortable with AI tools?’ And I don’t know the answer,” Dr. Popescu says. “How to use AI as an aid in the decision-making process is something that’s not currently taught.”

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