Trauma

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.

Adults with posttraumatic stress disorder (PTSD) have smaller cerebellums than unaffected adults, suggesting that this part of the brain may be a potential therapeutic target.

According to recent research on more than 4000 adults, cerebellum volume was significantly smaller (by about 2%) in those with PTSD than in trauma-exposed and trauma-naive controls without PTSD.

“The differences were largely within the posterior lobe, where a lot of the more cognitive functions attributed to the cerebellum seem to localize, as well as the vermis, which is linked to a lot of emotional processing functions,” lead author Ashley Huggins, PhD, said in a news release.

“If we know what areas are implicated, then we can start to focus interventions like brain stimulation on the cerebellum and potentially improve treatment outcomes,” said Dr. Huggins, who worked on the study while a postdoctoral researcher in the lab of Rajendra A. Morey, MD, at Duke University, Durham, North Carolina, and is now at the University of Arizona, Tucson.

While the cerebellum is known for its role in coordinating movement and balance, it also plays a key role in emotions and memory, which are affected by PTSD.

Smaller cerebellar volume has been observed in some adult and pediatric populations with PTSD.

However, those studies have been limited by either small sample sizes, the failure to consider key neuroanatomical subdivisions of the cerebellum, or a focus on certain populations such as veterans of sexual assault victims with PTSD.

To overcome these limitations, the researchers conducted a mega-analysis of total and subregional cerebellar volumes in a large, multicohort dataset from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Psychiatric Genomics Consortium PTSD workgroup that was published online on January 10, 2024, in Molecular Psychiatry.

They employed a novel, standardized ENIGMA cerebellum parcellation protocol to quantify cerebellar lobule volumes using structural MRI data from 1642 adults with PTSD and 2573 healthy controls without PTSD (88% trauma-exposed and 12% trauma-naive).

After adjustment for age, gender, and total intracranial volume, PTSD was associated with significant gray and white matter reductions of the cerebellum.

People with PTSD demonstrated smaller total cerebellum volume as well as reduced volume in subregions primarily within the posterior cerebellum, vermis, and flocculonodular cerebellum than controls.

In general, PTSD severity was more robustly associated with cerebellar volume differences than PTSD diagnosis.

Focusing purely on a “yes-or-no” categorical diagnosis didn’t always provide the clearest picture. “When we looked at PTSD severity, people who had more severe forms of the disorder had an even smaller cerebellar volume,” Dr. Huggins explained in the news release.

Novel Treatment Target

These findings add to “an emerging literature that underscores the relevance of cerebellar structure in the pathophysiology of PTSD,” the researchers noted.

They caution that despite the significant findings suggesting associations between PTSD and smaller cerebellar volumes, effect sizes were small. “As such, it is unlikely that structural cerebellar volumes alone will provide a clinically useful biomarker (eg, for individual-level prediction).”

Nonetheless, the study highlights the cerebellum as a “novel treatment target that may be leveraged to improve treatment outcomes for PTSD,” they wrote.

They noted that prior work has shown that the cerebellum is sensitive to external modulation. For example, noninvasive brain stimulation of the cerebellum has been shown to modulate cognitive, emotional, and social processes commonly disrupted in PTSD.

Commenting on this research, Cyrus A. Raji, MD, PhD, associate professor of radiology and neurology at Washington University in St. Louis, noted that this “large neuroimaging study links PTSD to cerebellar volume loss.”

“However, PTSD and traumatic brain injury frequently co-occur, and PTSD also frequently arises after TBI. Additionally, TBI is strongly linked to cerebellar volume loss,” Dr. Raji pointed out.

“Future studies need to better delineate volume loss from these conditions, especially when they are comorbid, though the expectation is these effects would be additive with TBI being the initial and most severe driving force,” Dr. Raji added.

The research had no commercial funding. Author disclosures are listed with the original article. Dr. Raji is a consultant for Brainreader, Apollo Health, Pacific Neuroscience Foundation, and Neurevolution Medicine LLC.
 

A version of this article appears on Medscape.com.

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series telling these stories.

A week earlier I’d had a heart surgery and was heading out for a post-op appointment when I saw it: I had a flat tire. It didn’t make sense. The tire was brand new, and there was no puncture. But it was flat.

I swapped out the flat for the spare and went off base to a tire shop. While I was there, my surgeon’s office called and rescheduled my appointment for a couple of hours later. That was lucky because by the time the tire was fixed, I had just enough time to get there.

The hospital is right near I-35 in San Antonio, Texas. I got off the freeway and onto the access road and paused to turn into the parking lot. That’s when I heard an enormous crash.

I saw a big poof of white smoke, and a car barreled off the freeway and came rolling down the embankment.

When the car hit the access road, I saw a woman ejected through the windshield. She bounced and landed in the road about 25 feet in front of me.

I put my car in park, grabbed my face mask and gloves, and started running toward her. But another vehicle — a truck towing a trailer — came from behind to drive around me. The driver didn’t realize what had happened and couldn’t stop in time…

The trailer ran over her.

I didn’t know if anyone could’ve survived that, but I went to her. I saw several other bystanders, but they were frozen in shock. I was praying, dear God, if she’s alive, let me do whatever I need to do to save her life.

It was a horrible scene. This poor lady was in a bloody heap in the middle of the road. Her right arm was twisted up under her neck so tightly, she was choking herself. So, the first thing I did was straighten her arm out to protect her airway.

I started yelling at people, “Call 9-1-1! Run to the hospital! Let them know there’s an accident out here, and I need help!”

The woman had a pulse, but it was super rapid. On first glance, she clearly had multiple fractures and a bad head bleed. With the sheer number of times she’d been injured, I didn’t know what was going on internally, but it was bad. She was gargling on her own blood and spitting it up. She was drowning.

A couple of technicians from the hospital came and brought me a tiny emergency kit. It had a blood pressure cuff and an oral airway. All the vital signs indicated the lady was going into shock. She’d lost a lot of blood on the pavement.

I was able to get the oral airway in. A few minutes later, a fire chief showed up. By now, the traffic had backed up so badly, the emergency vehicles couldn’t get in. But he managed to get there another way and gave me a cervical collar (C collar) and an Ambu bag.

I was hyper-focused on what I could do at that moment and what I needed to do next. Her stats were going down, but she still had a pulse. If she lost the pulse or went into a lethal rhythm, I’d have to start cardiopulmonary resuscitation (CPR). I asked the other people, but nobody else knew CPR, so I wouldn’t have help.

I could tell the lady had a pelvic fracture, and we needed to stabilize her. I directed people how to hold her neck safely and log-roll her flat on the ground. I also needed to put pressure on the back of her head because of all the bleeding. I got people to give me their clothes and tried to do that as I was bagging her.

The windows of her vehicle had all been blown out. I asked somebody to go find her purse with her ID. Then I noticed something …

My heart jumped into my stomach.

A car seat. There was an empty child’s car seat in the back of the car.

I started yelling at everyone, “Look for a baby! Go up and down the embankment and across the road. There might have been a baby in the car!”

But there wasn’t. Thank God. She hadn’t been driving with her child.

At that point, a paramedic came running from behind all the traffic. We did life support together until the ambulance finally arrived.

Emergency medical services got an intravenous line in and used medical anti-shock trousers. Thankfully, I already had the C collar on, and we’d been bagging her, so they could load her very quickly.

I got rid of my bloody gloves. I told a police officer I would come back. And then I went to my doctor’s appointment.

The window at my doctor’s office faced the access road, so the people there had seen all the traffic. They asked me what happened, and I said, “It was me. I saw it happen. I tried to help.” I was a little frazzled.

When I got back to the scene, the police and the fire chief kept thanking me for stopping. Why wouldn’t I stop? It was astounding to realize that they imagined somebody wouldn’t stop in a situation like this.

They told me the lady was alive. She was in the intensive care unit in critical condition, but she had survived. At that moment, I had this overwhelming feeling: God had put me in this exact place at the exact time to save her life.

Looking back, I think about how God ordered my steps. Without the mysterious flat tire, I would’ve gone to the hospital earlier. If my appointment hadn’t been rescheduled, I wouldn’t have been on the access road. All those events brought me there.

Several months later, the woman’s family contacted me and asked if we could meet. I found out more about her injuries. She’d had multiple skull fractures, facial fractures, and a broken jaw. Her upper arm was broken in three places. Her clavicle was broken. She had internal bleeding, a pelvic fracture, and a broken leg. She was 28 years old.

She’d had multiple surgeries, spent 2 months in the ICU, and another 3 months in intensive rehab. But she survived. It was incredible.

We all met up at a McDonald’s. First, her little son — who was the baby I thought might have been in the car — ran up to me and said, “Thank you for saving my mommy’s life.”

Then I turned, and there she was — a beautiful lady looking at me with awe and crying, saying, “It’s me.”

She obviously had gone through a transformation from all the injuries and the medications. She had a little bit of a speech delay, but mentally, she was there. She could walk.

She said, “You’re my angel. God put you there to save my life.” Her family all came up and hugged me. It was so beautiful.

She told me about the accident. She’d been speeding that day, zigzagging through lanes to get around the traffic. And she didn’t have her seatbelt on. She’d driven onto the shoulder to try to pass everyone, but it started narrowing. She clipped somebody’s bumper, went into a tailspin, and collided with a second vehicle, which caused her to flip over and down the embankment.

“God’s given me a new lease on life,” she said, “a fresh start. I will forever wear my seatbelt. And I’m going to do whatever I can to give back to other people because I don’t even feel like I deserve this.”

I just cried.

I’ve been a nurse for 29 years, first on the civilian side and later in the military. I’ve led codes and responded to trauma in a hospital setting or a deployed environment. I was well prepared to do what I did. But doing it under such stress with adrenaline bombarding me ... I’m amazed. I just think God’s hand was on me.

At that time, I was personally going through some things. After my heart surgery, I was in an emotional place where I didn’t feel loved or valued. But when I had that realization — when I knew that I was meant to be there to save her life, I also got the very clear message that I was valued and loved so much.

I know I have a very strong purpose. That day changed my life.
 

US Air Force Lt. Col. Anne Staley is the officer in charge of the Military Training Network, a division of the Defense Health Agency Education and Training Directorate in San Antonio, Texas.

A version of this article appeared on Medscape.com.

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series telling these stories.

A week earlier I’d had a heart surgery and was heading out for a post-op appointment when I saw it: I had a flat tire. It didn’t make sense. The tire was brand new, and there was no puncture. But it was flat.

I swapped out the flat for the spare and went off base to a tire shop. While I was there, my surgeon’s office called and rescheduled my appointment for a couple of hours later. That was lucky because by the time the tire was fixed, I had just enough time to get there.

The hospital is right near I-35 in San Antonio, Texas. I got off the freeway and onto the access road and paused to turn into the parking lot. That’s when I heard an enormous crash.

I saw a big poof of white smoke, and a car barreled off the freeway and came rolling down the embankment.

When the car hit the access road, I saw a woman ejected through the windshield. She bounced and landed in the road about 25 feet in front of me.

I put my car in park, grabbed my face mask and gloves, and started running toward her. But another vehicle — a truck towing a trailer — came from behind to drive around me. The driver didn’t realize what had happened and couldn’t stop in time…

The trailer ran over her.

I didn’t know if anyone could’ve survived that, but I went to her. I saw several other bystanders, but they were frozen in shock. I was praying, dear God, if she’s alive, let me do whatever I need to do to save her life.

It was a horrible scene. This poor lady was in a bloody heap in the middle of the road. Her right arm was twisted up under her neck so tightly, she was choking herself. So, the first thing I did was straighten her arm out to protect her airway.

I started yelling at people, “Call 9-1-1! Run to the hospital! Let them know there’s an accident out here, and I need help!”

The woman had a pulse, but it was super rapid. On first glance, she clearly had multiple fractures and a bad head bleed. With the sheer number of times she’d been injured, I didn’t know what was going on internally, but it was bad. She was gargling on her own blood and spitting it up. She was drowning.

A couple of technicians from the hospital came and brought me a tiny emergency kit. It had a blood pressure cuff and an oral airway. All the vital signs indicated the lady was going into shock. She’d lost a lot of blood on the pavement.

I was able to get the oral airway in. A few minutes later, a fire chief showed up. By now, the traffic had backed up so badly, the emergency vehicles couldn’t get in. But he managed to get there another way and gave me a cervical collar (C collar) and an Ambu bag.

I was hyper-focused on what I could do at that moment and what I needed to do next. Her stats were going down, but she still had a pulse. If she lost the pulse or went into a lethal rhythm, I’d have to start cardiopulmonary resuscitation (CPR). I asked the other people, but nobody else knew CPR, so I wouldn’t have help.

I could tell the lady had a pelvic fracture, and we needed to stabilize her. I directed people how to hold her neck safely and log-roll her flat on the ground. I also needed to put pressure on the back of her head because of all the bleeding. I got people to give me their clothes and tried to do that as I was bagging her.

The windows of her vehicle had all been blown out. I asked somebody to go find her purse with her ID. Then I noticed something …

My heart jumped into my stomach.

A car seat. There was an empty child’s car seat in the back of the car.

I started yelling at everyone, “Look for a baby! Go up and down the embankment and across the road. There might have been a baby in the car!”

But there wasn’t. Thank God. She hadn’t been driving with her child.

At that point, a paramedic came running from behind all the traffic. We did life support together until the ambulance finally arrived.

Emergency medical services got an intravenous line in and used medical anti-shock trousers. Thankfully, I already had the C collar on, and we’d been bagging her, so they could load her very quickly.

I got rid of my bloody gloves. I told a police officer I would come back. And then I went to my doctor’s appointment.

The window at my doctor’s office faced the access road, so the people there had seen all the traffic. They asked me what happened, and I said, “It was me. I saw it happen. I tried to help.” I was a little frazzled.

When I got back to the scene, the police and the fire chief kept thanking me for stopping. Why wouldn’t I stop? It was astounding to realize that they imagined somebody wouldn’t stop in a situation like this.

They told me the lady was alive. She was in the intensive care unit in critical condition, but she had survived. At that moment, I had this overwhelming feeling: God had put me in this exact place at the exact time to save her life.

Looking back, I think about how God ordered my steps. Without the mysterious flat tire, I would’ve gone to the hospital earlier. If my appointment hadn’t been rescheduled, I wouldn’t have been on the access road. All those events brought me there.

Several months later, the woman’s family contacted me and asked if we could meet. I found out more about her injuries. She’d had multiple skull fractures, facial fractures, and a broken jaw. Her upper arm was broken in three places. Her clavicle was broken. She had internal bleeding, a pelvic fracture, and a broken leg. She was 28 years old.

She’d had multiple surgeries, spent 2 months in the ICU, and another 3 months in intensive rehab. But she survived. It was incredible.

We all met up at a McDonald’s. First, her little son — who was the baby I thought might have been in the car — ran up to me and said, “Thank you for saving my mommy’s life.”

Then I turned, and there she was — a beautiful lady looking at me with awe and crying, saying, “It’s me.”

She obviously had gone through a transformation from all the injuries and the medications. She had a little bit of a speech delay, but mentally, she was there. She could walk.

She said, “You’re my angel. God put you there to save my life.” Her family all came up and hugged me. It was so beautiful.

She told me about the accident. She’d been speeding that day, zigzagging through lanes to get around the traffic. And she didn’t have her seatbelt on. She’d driven onto the shoulder to try to pass everyone, but it started narrowing. She clipped somebody’s bumper, went into a tailspin, and collided with a second vehicle, which caused her to flip over and down the embankment.

“God’s given me a new lease on life,” she said, “a fresh start. I will forever wear my seatbelt. And I’m going to do whatever I can to give back to other people because I don’t even feel like I deserve this.”

I just cried.

I’ve been a nurse for 29 years, first on the civilian side and later in the military. I’ve led codes and responded to trauma in a hospital setting or a deployed environment. I was well prepared to do what I did. But doing it under such stress with adrenaline bombarding me ... I’m amazed. I just think God’s hand was on me.

At that time, I was personally going through some things. After my heart surgery, I was in an emotional place where I didn’t feel loved or valued. But when I had that realization — when I knew that I was meant to be there to save her life, I also got the very clear message that I was valued and loved so much.

I know I have a very strong purpose. That day changed my life.
 

US Air Force Lt. Col. Anne Staley is the officer in charge of the Military Training Network, a division of the Defense Health Agency Education and Training Directorate in San Antonio, Texas.

A version of this article appeared on Medscape.com.

Emergencies happen anywhere and anytime, and sometimes, medical professionals find themselves in situations where they are the only ones who can help. Is There a Doctor in the House? is a series telling these stories.

A week earlier I’d had a heart surgery and was heading out for a post-op appointment when I saw it: I had a flat tire. It didn’t make sense. The tire was brand new, and there was no puncture. But it was flat.

I swapped out the flat for the spare and went off base to a tire shop. While I was there, my surgeon’s office called and rescheduled my appointment for a couple of hours later. That was lucky because by the time the tire was fixed, I had just enough time to get there.

The hospital is right near I-35 in San Antonio, Texas. I got off the freeway and onto the access road and paused to turn into the parking lot. That’s when I heard an enormous crash.

I saw a big poof of white smoke, and a car barreled off the freeway and came rolling down the embankment.

When the car hit the access road, I saw a woman ejected through the windshield. She bounced and landed in the road about 25 feet in front of me.

I put my car in park, grabbed my face mask and gloves, and started running toward her. But another vehicle — a truck towing a trailer — came from behind to drive around me. The driver didn’t realize what had happened and couldn’t stop in time…

The trailer ran over her.

I didn’t know if anyone could’ve survived that, but I went to her. I saw several other bystanders, but they were frozen in shock. I was praying, dear God, if she’s alive, let me do whatever I need to do to save her life.

It was a horrible scene. This poor lady was in a bloody heap in the middle of the road. Her right arm was twisted up under her neck so tightly, she was choking herself. So, the first thing I did was straighten her arm out to protect her airway.

I started yelling at people, “Call 9-1-1! Run to the hospital! Let them know there’s an accident out here, and I need help!”

The woman had a pulse, but it was super rapid. On first glance, she clearly had multiple fractures and a bad head bleed. With the sheer number of times she’d been injured, I didn’t know what was going on internally, but it was bad. She was gargling on her own blood and spitting it up. She was drowning.

A couple of technicians from the hospital came and brought me a tiny emergency kit. It had a blood pressure cuff and an oral airway. All the vital signs indicated the lady was going into shock. She’d lost a lot of blood on the pavement.

I was able to get the oral airway in. A few minutes later, a fire chief showed up. By now, the traffic had backed up so badly, the emergency vehicles couldn’t get in. But he managed to get there another way and gave me a cervical collar (C collar) and an Ambu bag.

I was hyper-focused on what I could do at that moment and what I needed to do next. Her stats were going down, but she still had a pulse. If she lost the pulse or went into a lethal rhythm, I’d have to start cardiopulmonary resuscitation (CPR). I asked the other people, but nobody else knew CPR, so I wouldn’t have help.

I could tell the lady had a pelvic fracture, and we needed to stabilize her. I directed people how to hold her neck safely and log-roll her flat on the ground. I also needed to put pressure on the back of her head because of all the bleeding. I got people to give me their clothes and tried to do that as I was bagging her.

The windows of her vehicle had all been blown out. I asked somebody to go find her purse with her ID. Then I noticed something …

My heart jumped into my stomach.

A car seat. There was an empty child’s car seat in the back of the car.

I started yelling at everyone, “Look for a baby! Go up and down the embankment and across the road. There might have been a baby in the car!”

But there wasn’t. Thank God. She hadn’t been driving with her child.

At that point, a paramedic came running from behind all the traffic. We did life support together until the ambulance finally arrived.

Emergency medical services got an intravenous line in and used medical anti-shock trousers. Thankfully, I already had the C collar on, and we’d been bagging her, so they could load her very quickly.

I got rid of my bloody gloves. I told a police officer I would come back. And then I went to my doctor’s appointment.

The window at my doctor’s office faced the access road, so the people there had seen all the traffic. They asked me what happened, and I said, “It was me. I saw it happen. I tried to help.” I was a little frazzled.

When I got back to the scene, the police and the fire chief kept thanking me for stopping. Why wouldn’t I stop? It was astounding to realize that they imagined somebody wouldn’t stop in a situation like this.

They told me the lady was alive. She was in the intensive care unit in critical condition, but she had survived. At that moment, I had this overwhelming feeling: God had put me in this exact place at the exact time to save her life.

Looking back, I think about how God ordered my steps. Without the mysterious flat tire, I would’ve gone to the hospital earlier. If my appointment hadn’t been rescheduled, I wouldn’t have been on the access road. All those events brought me there.

Several months later, the woman’s family contacted me and asked if we could meet. I found out more about her injuries. She’d had multiple skull fractures, facial fractures, and a broken jaw. Her upper arm was broken in three places. Her clavicle was broken. She had internal bleeding, a pelvic fracture, and a broken leg. She was 28 years old.

She’d had multiple surgeries, spent 2 months in the ICU, and another 3 months in intensive rehab. But she survived. It was incredible.

We all met up at a McDonald’s. First, her little son — who was the baby I thought might have been in the car — ran up to me and said, “Thank you for saving my mommy’s life.”

Then I turned, and there she was — a beautiful lady looking at me with awe and crying, saying, “It’s me.”

She obviously had gone through a transformation from all the injuries and the medications. She had a little bit of a speech delay, but mentally, she was there. She could walk.

She said, “You’re my angel. God put you there to save my life.” Her family all came up and hugged me. It was so beautiful.

She told me about the accident. She’d been speeding that day, zigzagging through lanes to get around the traffic. And she didn’t have her seatbelt on. She’d driven onto the shoulder to try to pass everyone, but it started narrowing. She clipped somebody’s bumper, went into a tailspin, and collided with a second vehicle, which caused her to flip over and down the embankment.

“God’s given me a new lease on life,” she said, “a fresh start. I will forever wear my seatbelt. And I’m going to do whatever I can to give back to other people because I don’t even feel like I deserve this.”

I just cried.

I’ve been a nurse for 29 years, first on the civilian side and later in the military. I’ve led codes and responded to trauma in a hospital setting or a deployed environment. I was well prepared to do what I did. But doing it under such stress with adrenaline bombarding me ... I’m amazed. I just think God’s hand was on me.

At that time, I was personally going through some things. After my heart surgery, I was in an emotional place where I didn’t feel loved or valued. But when I had that realization — when I knew that I was meant to be there to save her life, I also got the very clear message that I was valued and loved so much.

I know I have a very strong purpose. That day changed my life.
 

US Air Force Lt. Col. Anne Staley is the officer in charge of the Military Training Network, a division of the Defense Health Agency Education and Training Directorate in San Antonio, Texas.

A version of this article appeared on Medscape.com.

A power outage, like the 1977 blackout in New York City, can lead to an increase in violent crime. However, complete darkness can also have an upside, as it can encourage intimacy and subsequently boost birth rates. The Christmas season, sometimes called the festival of love, appears to stimulate human interactions. Yet this, also, has its downsides, as recently reported by Dr. Nikolaos Pyrgidis and other urologists at Ludwig Maximilian University of Munich in Germany. The less cheerful aspect of the holiday season is penile fractures.

The team found that the Christmas period, in particular, is that bit more risky for this injury after they evaluated data from about 3400 men (average age 42) treated for penile fractures between 2005 and 2021. The data was provided by Germany’s Federal Bureau of Statistics.

Out of the 3400 penile fractures that were reported during this period, 40 (1.2%) occurred over 51 Christmas days (from 24th to 26th December each year). The daily incidence rate of penile fractures during the Christmas period was 0.78, with an incidence rate ratio (IRR) of 1.43. The authors note that, if every day were like Christmas, there would have been a 43% increase in penile fractures in Germany since 2005. Interestingly, only 28 (0.82%) penile fractures were reported during the New Year (from 31 December to 2 January in the period between 2005 and 2021), with an IRR of 0.98.

More generally, most patients with penile fractures were admitted to the hospital over the weekend (n=1322; IRR 1.58). Notably, Sunday saw the most admissions due to this injury, followed by Saturday. This suggests that men engaging in sexual activities on Saturday night bear the highest risk of penile fractures, followed by those active on Friday nights.

Penile fractures also increased in the summer months (n=929; IRR 1.11). But the COVID-19 pandemic (n=385; IRR 1.06) and the lockdowns (n=93; IRR 1.95%) did not impact the frequency of this injury.

Rare, Painful, and an Emergency

Penile fractures are a rare urological emergency. The tunica albuginea of one or both corpora cavernosa must tear to be considered problematic, as another team of authors reported in a recent publication. Involvement of the urethra and corpus spongiosum is also possible.

Injuries often occur during an erection because it makes the tunica albuginea stiffer and thinner than when the penis is flaccid. Patients report hearing a snap when the penis is forced into an angle during sexual activity. This was reportedly the case with German singer-song writer Dieter Bohlen, whose ex-girlfriend Nadja Abd El Farrag is said to have written in her book “Ungelogen”, or “Honestly”, that there was a sudden snap during an intimate moment one December night (Christmas?), after which she called the fire brigade in her distress.

Multiple Causes Possible

Other factors contributing to penile fractures include rolling over in bed onto an erect penis, forced bending to achieve detumescence, and blunt external traumas like kicks.

Some penile fractures can be caused by patients “kneading and ripping” their erect penis to quickly reduce swelling. In an Iranian study, 269 out of 352 patients (76%) who underwent this process, known as “ taqaandan” in Iran, suffered a penile fracture.

Penile fractures can also occur in children, as evidenced by the case history of a 7-year-old boy described a few years ago in the journal Urology where the cause was a fall onto the penis.

Immediate Action Required

The treatment of choice for a fresh penile fracture is surgical repair of the tunica albuginea defect and, if necessary, the urethra. Timely surgical intervention yields significantly better long-term outcomes than conservative therapy regarding late complications such as erectile dysfunction and penile curvature. It also reduces the rate of early complications, such as severe corporal infections. Conservative therapy should be reserved for patients who explicitly refuse surgical intervention after thorough consultation.

This article was translated from Univadis Germany using ChatGPT followed by human editing.

A version of this article appeared on Medscape.com.

A power outage, like the 1977 blackout in New York City, can lead to an increase in violent crime. However, complete darkness can also have an upside, as it can encourage intimacy and subsequently boost birth rates. The Christmas season, sometimes called the festival of love, appears to stimulate human interactions. Yet this, also, has its downsides, as recently reported by Dr. Nikolaos Pyrgidis and other urologists at Ludwig Maximilian University of Munich in Germany. The less cheerful aspect of the holiday season is penile fractures.

The team found that the Christmas period, in particular, is that bit more risky for this injury after they evaluated data from about 3400 men (average age 42) treated for penile fractures between 2005 and 2021. The data was provided by Germany’s Federal Bureau of Statistics.

Out of the 3400 penile fractures that were reported during this period, 40 (1.2%) occurred over 51 Christmas days (from 24th to 26th December each year). The daily incidence rate of penile fractures during the Christmas period was 0.78, with an incidence rate ratio (IRR) of 1.43. The authors note that, if every day were like Christmas, there would have been a 43% increase in penile fractures in Germany since 2005. Interestingly, only 28 (0.82%) penile fractures were reported during the New Year (from 31 December to 2 January in the period between 2005 and 2021), with an IRR of 0.98.

More generally, most patients with penile fractures were admitted to the hospital over the weekend (n=1322; IRR 1.58). Notably, Sunday saw the most admissions due to this injury, followed by Saturday. This suggests that men engaging in sexual activities on Saturday night bear the highest risk of penile fractures, followed by those active on Friday nights.

Penile fractures also increased in the summer months (n=929; IRR 1.11). But the COVID-19 pandemic (n=385; IRR 1.06) and the lockdowns (n=93; IRR 1.95%) did not impact the frequency of this injury.

Rare, Painful, and an Emergency

Penile fractures are a rare urological emergency. The tunica albuginea of one or both corpora cavernosa must tear to be considered problematic, as another team of authors reported in a recent publication. Involvement of the urethra and corpus spongiosum is also possible.

Injuries often occur during an erection because it makes the tunica albuginea stiffer and thinner than when the penis is flaccid. Patients report hearing a snap when the penis is forced into an angle during sexual activity. This was reportedly the case with German singer-song writer Dieter Bohlen, whose ex-girlfriend Nadja Abd El Farrag is said to have written in her book “Ungelogen”, or “Honestly”, that there was a sudden snap during an intimate moment one December night (Christmas?), after which she called the fire brigade in her distress.

Multiple Causes Possible

Other factors contributing to penile fractures include rolling over in bed onto an erect penis, forced bending to achieve detumescence, and blunt external traumas like kicks.

Some penile fractures can be caused by patients “kneading and ripping” their erect penis to quickly reduce swelling. In an Iranian study, 269 out of 352 patients (76%) who underwent this process, known as “ taqaandan” in Iran, suffered a penile fracture.

Penile fractures can also occur in children, as evidenced by the case history of a 7-year-old boy described a few years ago in the journal Urology where the cause was a fall onto the penis.

Immediate Action Required

The treatment of choice for a fresh penile fracture is surgical repair of the tunica albuginea defect and, if necessary, the urethra. Timely surgical intervention yields significantly better long-term outcomes than conservative therapy regarding late complications such as erectile dysfunction and penile curvature. It also reduces the rate of early complications, such as severe corporal infections. Conservative therapy should be reserved for patients who explicitly refuse surgical intervention after thorough consultation.

This article was translated from Univadis Germany using ChatGPT followed by human editing.

A version of this article appeared on Medscape.com.

A power outage, like the 1977 blackout in New York City, can lead to an increase in violent crime. However, complete darkness can also have an upside, as it can encourage intimacy and subsequently boost birth rates. The Christmas season, sometimes called the festival of love, appears to stimulate human interactions. Yet this, also, has its downsides, as recently reported by Dr. Nikolaos Pyrgidis and other urologists at Ludwig Maximilian University of Munich in Germany. The less cheerful aspect of the holiday season is penile fractures.

The team found that the Christmas period, in particular, is that bit more risky for this injury after they evaluated data from about 3400 men (average age 42) treated for penile fractures between 2005 and 2021. The data was provided by Germany’s Federal Bureau of Statistics.

Out of the 3400 penile fractures that were reported during this period, 40 (1.2%) occurred over 51 Christmas days (from 24th to 26th December each year). The daily incidence rate of penile fractures during the Christmas period was 0.78, with an incidence rate ratio (IRR) of 1.43. The authors note that, if every day were like Christmas, there would have been a 43% increase in penile fractures in Germany since 2005. Interestingly, only 28 (0.82%) penile fractures were reported during the New Year (from 31 December to 2 January in the period between 2005 and 2021), with an IRR of 0.98.

More generally, most patients with penile fractures were admitted to the hospital over the weekend (n=1322; IRR 1.58). Notably, Sunday saw the most admissions due to this injury, followed by Saturday. This suggests that men engaging in sexual activities on Saturday night bear the highest risk of penile fractures, followed by those active on Friday nights.

Penile fractures also increased in the summer months (n=929; IRR 1.11). But the COVID-19 pandemic (n=385; IRR 1.06) and the lockdowns (n=93; IRR 1.95%) did not impact the frequency of this injury.

Rare, Painful, and an Emergency

Penile fractures are a rare urological emergency. The tunica albuginea of one or both corpora cavernosa must tear to be considered problematic, as another team of authors reported in a recent publication. Involvement of the urethra and corpus spongiosum is also possible.

Injuries often occur during an erection because it makes the tunica albuginea stiffer and thinner than when the penis is flaccid. Patients report hearing a snap when the penis is forced into an angle during sexual activity. This was reportedly the case with German singer-song writer Dieter Bohlen, whose ex-girlfriend Nadja Abd El Farrag is said to have written in her book “Ungelogen”, or “Honestly”, that there was a sudden snap during an intimate moment one December night (Christmas?), after which she called the fire brigade in her distress.

Multiple Causes Possible

Other factors contributing to penile fractures include rolling over in bed onto an erect penis, forced bending to achieve detumescence, and blunt external traumas like kicks.

Some penile fractures can be caused by patients “kneading and ripping” their erect penis to quickly reduce swelling. In an Iranian study, 269 out of 352 patients (76%) who underwent this process, known as “ taqaandan” in Iran, suffered a penile fracture.

Penile fractures can also occur in children, as evidenced by the case history of a 7-year-old boy described a few years ago in the journal Urology where the cause was a fall onto the penis.

Immediate Action Required

The treatment of choice for a fresh penile fracture is surgical repair of the tunica albuginea defect and, if necessary, the urethra. Timely surgical intervention yields significantly better long-term outcomes than conservative therapy regarding late complications such as erectile dysfunction and penile curvature. It also reduces the rate of early complications, such as severe corporal infections. Conservative therapy should be reserved for patients who explicitly refuse surgical intervention after thorough consultation.

This article was translated from Univadis Germany using ChatGPT followed by human editing.

A version of this article appeared on Medscape.com.

Early childhood trauma alters brain function in adults, according to new research.

In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains. 

The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.

“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”

The findings were published in JAMA Network Open.
 

Changes in Reactivity 

“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.

“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.

She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately. 

Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.

Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls. 

Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.

In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.

“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
 

‘Important Next Step’ 

“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary. 

They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.” 

Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.” 
 

Epigenetic Changes? 

Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.

“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.

“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.” 

No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work. 

A version of this article appeared on Medscape.com.

Early childhood trauma alters brain function in adults, according to new research.

In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains. 

The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.

“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”

The findings were published in JAMA Network Open.
 

Changes in Reactivity 

“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.

“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.

She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately. 

Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.

Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls. 

Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.

In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.

“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
 

‘Important Next Step’ 

“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary. 

They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.” 

Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.” 
 

Epigenetic Changes? 

Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.

“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.

“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.” 

No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work. 

A version of this article appeared on Medscape.com.

Early childhood trauma alters brain function in adults, according to new research.

In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains. 

The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.

“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”

The findings were published in JAMA Network Open.
 

Changes in Reactivity 

“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.

“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.

She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately. 

Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.

Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls. 

Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.

In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.

“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
 

‘Important Next Step’ 

“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary. 

They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.” 

Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.” 
 

Epigenetic Changes? 

Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.

“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.

“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.” 

No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work. 

A version of this article appeared on Medscape.com.

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

An experimental therapy that uses deep brain stimulation (DBS) to deliver precise electrical pulses to an area deep inside the brain restored executive function in patients with moderate to severe traumatic brain injury (msTBI) and chronic sequelae.

Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.

This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.

Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.

After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.

Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.

The findings were published online Dec. 4 in Nature Medicine.

“No Trivial Feat”

An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.

Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.

The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.

Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.

To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.

“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”

“A Moving Target”

Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.

“It was a literal moving target,” Dr. Henderson said.

In the beginning, investigators used microelectrode recording to “listen” to individual neurons to see which ones weren’t firing correctly.

When that method failed to offer the precise information needed for electrode placement, the investigators switched to neuroimaging, which allowed them to complete the surgery more quickly and accurately.

Participants remained in the hospital 1-2 days after surgery. They returned for postoperative imaging 30 days after surgery and were randomly assigned to different schedules for a 14-day titration period to optimize DBS stimulation.

The primary outcome was a 10% improvement on part B of the trail-making test, a neuropsychological test that measures executive functioning.

After 90 days of 12-hour daily DBS treatments, participants’ scores increased 15%–52% (average 32%) from baseline. Participants also reported an average of 33% decline in fatigue, one of the most common side effects of msTBI, and an average 80% improvement in attention.

The main safety risk during the 3- to-4-hour procedure is bleeding, which didn’t affect any of the participants in this study. One participant developed a surgical site infection, but all other side effects were mild.

After the 90-day treatment period, the study plan called for patients to be randomly assigned to a blinded withdrawal of treatment, with the DBS turned off for 21 days. Two of the patients declined to be randomized. DBS was turned off in one participant while the other two continued as normal.

After 3 weeks, the patient whose DBS was turned off showed a 34% decline on cognitive tests. The device was reactivated after the study and that participant has since reported improvements.

The DBS devices continue to function in all participants. Although their performance is not being measured as part of the study, anecdotal reports indicate sustained improvement in executive functioning.

“The brain injury causes this global down-regulation of brain function and what we think that this is doing is turning that back up again,” Dr. Henderson said. “At a very simplistic level, what we’re trying to do is turn the lights back up after the dimmer switch is switched down from the injury.”

New Hope

TBI patients are usually treated aggressively during the first year, when significant improvements are most likely, but there are few therapeutic options beyond that time, said neurologist Javier Cardenas, MD, who commented on the findings for this article.

“Many providers throw their hands up after a year in terms of intervention and then we’re always looking at potential declines over time,” said Dr. Cardenas, director of the Concussion and Brain Injury Center at the Rockefeller Neuroscience Institution, West Virginia University, Morgantown. “Most people plateau and don’t decline but we’re always worried about a secondary decline in traumatic brain injury.”Surgery is usually only employed immediately following the brain injury. The notion of surgery as a therapeutic option years after the initial assault on the brain is novel, said Jimmy Yang, MD, assistant professor of neurologic surgery at Ohio State University College of Medicine, Columbus, who commented on the findings for this article.

“While deep brain stimulation surgery in clinical practice is specifically tailored to each patient we treat, this study goes a step further by integrating research tools that have not yet made it to the clinical realm,” Dr. Yang said. “As a result, while these methods are not commonly used in clinical care, the overall strategy highlights how research advances are linked to clinical advances.”

Investigators are working to secure funding for a larger phase 2 trial.

“With millions of people affected by traumatic brain injury but without effective therapies, this study brings hope that options are on the horizon to help these patients,” Dr. Yang said.

The study was supported by funding from the National Institute of Health BRAIN Initiative and a grant from the Translational Science Center at Weill Cornell Medical College. Surgical implants were provided by Medtronic. Dr. Henderson and Dr. Schiff are listed as inventors on several patent applications for the experimental DBS therapy described in the study. Dr. Cardenas and Dr. Yang report no relevant financial relationships.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

A recent review by Hadanny and colleagues recommends hyperbaric oxygen therapy (HBOT) for acute moderate to severe traumatic brain injury (TBI) and selected patients with prolonged postconcussive syndrome.

This article piqued my curiosity because I trained in HBOT more than 20 years ago. As a passionate scuba diver, my motivation was to master treatment for air embolism and decompression illness. Thankfully, these diving accidents are rare. However, I used HBOT for nonhealing wounds, and its efficacy was sometimes remarkable.
 

Paradoxical results with oxygen therapy

Although it may seem self-evident that “more oxygen is better” for medical illness, this is not necessarily true. I recently interviewed Ola Didrik Saugstad, MD, who demonstrated that the traditional practice of resuscitating newborns with 100% oxygen was more toxic than resuscitation with air (which contains 21% oxygen). His counterintuitive discovery led to a lifesaving change in the international newborn resuscitation guidelines.

The Food and Drug Administration has approved HBOT for a wide variety of conditions, but some practitioners enthusiastically promote it for off-label indications. These include antiaging, autism, multiple sclerosis, and the aforementioned TBI.

More than 50 years ago, HBOT was proposed for stroke, another disorder where the brain has been deprived of oxygen. Despite obvious logic, clinical trials have been unconvincing. The FDA has not approved HBOT for stroke.
 

HBOT in practice

During HBOT, the patient breathes 100% oxygen while the whole body is pressurized within a hyperbaric chamber. The chamber’s construction allows pressures above normal sea level of 1.0 atmosphere absolute (ATA). For example, The U.S. Navy Treatment Table for decompression sickness recommends 100% oxygen at 2.8 ATA. Chambers may hold one or more patients at a time.

The frequency of therapy varies but often consists of 20-60 sessions lasting 90-120 minutes. For off-label use like TBI, patients usually pay out of pocket. Given the multiple treatments, costs can add up.
 

Inconsistent evidence and sham controls

The unwieldy 33-page evidence review by Hadanny and colleagues cites multiple studies supporting HBOT for TBI. However, many, if not all, suffer from methodological flaws. These include vague inclusion criteria, lack of a control group, small patient numbers, treatment at different times since injury, poorly defined or varying HBOT protocols, varying outcome measures, and superficial results analysis.

A sham or control arm is essential for HBOT research trials, given the potential placebo effect of placing a human being inside a large, high-tech, sealed tube for an hour or more. In some sham-controlled studies, which consisted of low-pressure oxygen (that is, 1.3 ATA as sham vs. 2.4 ATA as treatment), all groups experienced symptom improvement. The review authors argue that the low-dose HBOT sham arms were biologically active and that the improvements seen mean that both high- and low-dose HBOT is therapeutic. The alternative explanation is that the placebo effect accounted for improvement in both groups.

The late Michael Bennett, a world authority on hyperbaric and underwater medicine, doubted that conventional HBOT sham controls could genuinely have a therapeutic effect, and I agree. The upcoming HOT-POCS trial (discussed below) should answer the question more definitively.
 

Mechanisms of action and safety

Mechanisms of benefit for HBOT include increased oxygen availability and angiogenesis. Animal research suggests that it may reduce secondary cell death from TBI, through stabilization of the blood-brain barrier and inflammation reduction.

HBOT is generally safe and well tolerated. A retrospective analysis of 1.5 million outpatient hyperbaric treatments revealed that less than 1% were associated with adverse events. The most common were ear and sinus barotrauma. Because HBOT uses increased air pressure, patients must equalize their ears and sinuses. Those who cannot because of altered consciousness, anatomical defects, or congestion must undergo myringotomy or terminate therapy. Claustrophobia was the second most common adverse effect. Convulsions and tension pneumocephalus were rare.

Perhaps the most concerning risk of HBOT for patients with TBI is the potential waste of human and financial resources.
 

Desperate physicians and patients

As a neurologist who regularly treats patients with TBI, I share the review authors’ frustration regarding the limited efficacy of available treatments. However, the suboptimal efficacy of currently available therapy is insufficient justification to recommend HBOT.

With respect to chronic TBI, it is difficult to imagine how HBOT could reverse brain injury that has been present for months or years. No other therapy exists that reliably encourages neuronal regeneration or prevents the development of posttraumatic epilepsy.

Frank Conidi, MD, a board-certified sports neurologist and headache specialist, shared his thoughts via email. He agrees that HBOT may have a role in TBI, but after reviewing Hadanny and colleagues’ paper, he concluded that there is insufficient evidence for the use of HBOT in all forms of TBI. He would like to see large multicenter, well-designed studies with standardized pressures and duration and a standard definition of the various types of head injury.
 

Ongoing research

There are at least five ongoing trials on HBOT for TBI or postconcussive syndrome, including the well-designed placebo-controlled HOT-POCS study. The latter has a novel placebo gas system that addresses Hadanny and colleagues’ contention that even low-dose HBOT might be effective.

The placebo arm in HOT-POCS mimics the HBO environment but provides only 0.21 ATA of oxygen, the same as room air. The active arm provides 100% oxygen at 2.0 ATA. If patients in both arms improve, the benefit will be caused by a placebo response, not HBOT.
 

Conflict of interest

Another concern with the review is that all three authors are affiliated with Aviv Scientific. This company has an exclusive partnership with the world’s largest hyperbaric medicine and research facility, the Sagol Center at Shamir Medical Center in Be’er Ya’akov, Israel.

This conflict of interest does not a priori invalidate their conclusions. However, official HBOT guidelines from a leading organization like the Undersea and Hyperbaric Medicine Society or the American Academy of Neurology would be preferable.
 

Conclusion

There is an urgent unmet need for more effective treatments for postconcussive syndrome and chronic TBI. Despite tantalizing theoretical mechanisms as to why HBOT might promote brain healing after trauma, its efficacy remains unproven.

The review authors’ recommendations for HBOT seem premature. They are arguably a disservice to the many desperate patients and their families who will be tempted to expend valuable resources of time and money for an appealing but unproven therapy. Appropriately designed placebo-controlled studies such as HOT-POCS will help separate fact from wishful thinking.

Dr. Wilner is associate professor of neurology at University of Tennessee Health Science Center, Memphis. He reported a conflict of interest with Accordant Health Services.

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

A recent review by Hadanny and colleagues recommends hyperbaric oxygen therapy (HBOT) for acute moderate to severe traumatic brain injury (TBI) and selected patients with prolonged postconcussive syndrome.

This article piqued my curiosity because I trained in HBOT more than 20 years ago. As a passionate scuba diver, my motivation was to master treatment for air embolism and decompression illness. Thankfully, these diving accidents are rare. However, I used HBOT for nonhealing wounds, and its efficacy was sometimes remarkable.
 

Paradoxical results with oxygen therapy

Although it may seem self-evident that “more oxygen is better” for medical illness, this is not necessarily true. I recently interviewed Ola Didrik Saugstad, MD, who demonstrated that the traditional practice of resuscitating newborns with 100% oxygen was more toxic than resuscitation with air (which contains 21% oxygen). His counterintuitive discovery led to a lifesaving change in the international newborn resuscitation guidelines.

The Food and Drug Administration has approved HBOT for a wide variety of conditions, but some practitioners enthusiastically promote it for off-label indications. These include antiaging, autism, multiple sclerosis, and the aforementioned TBI.

More than 50 years ago, HBOT was proposed for stroke, another disorder where the brain has been deprived of oxygen. Despite obvious logic, clinical trials have been unconvincing. The FDA has not approved HBOT for stroke.
 

HBOT in practice

During HBOT, the patient breathes 100% oxygen while the whole body is pressurized within a hyperbaric chamber. The chamber’s construction allows pressures above normal sea level of 1.0 atmosphere absolute (ATA). For example, The U.S. Navy Treatment Table for decompression sickness recommends 100% oxygen at 2.8 ATA. Chambers may hold one or more patients at a time.

The frequency of therapy varies but often consists of 20-60 sessions lasting 90-120 minutes. For off-label use like TBI, patients usually pay out of pocket. Given the multiple treatments, costs can add up.
 

Inconsistent evidence and sham controls

The unwieldy 33-page evidence review by Hadanny and colleagues cites multiple studies supporting HBOT for TBI. However, many, if not all, suffer from methodological flaws. These include vague inclusion criteria, lack of a control group, small patient numbers, treatment at different times since injury, poorly defined or varying HBOT protocols, varying outcome measures, and superficial results analysis.

A sham or control arm is essential for HBOT research trials, given the potential placebo effect of placing a human being inside a large, high-tech, sealed tube for an hour or more. In some sham-controlled studies, which consisted of low-pressure oxygen (that is, 1.3 ATA as sham vs. 2.4 ATA as treatment), all groups experienced symptom improvement. The review authors argue that the low-dose HBOT sham arms were biologically active and that the improvements seen mean that both high- and low-dose HBOT is therapeutic. The alternative explanation is that the placebo effect accounted for improvement in both groups.

The late Michael Bennett, a world authority on hyperbaric and underwater medicine, doubted that conventional HBOT sham controls could genuinely have a therapeutic effect, and I agree. The upcoming HOT-POCS trial (discussed below) should answer the question more definitively.
 

Mechanisms of action and safety

Mechanisms of benefit for HBOT include increased oxygen availability and angiogenesis. Animal research suggests that it may reduce secondary cell death from TBI, through stabilization of the blood-brain barrier and inflammation reduction.

HBOT is generally safe and well tolerated. A retrospective analysis of 1.5 million outpatient hyperbaric treatments revealed that less than 1% were associated with adverse events. The most common were ear and sinus barotrauma. Because HBOT uses increased air pressure, patients must equalize their ears and sinuses. Those who cannot because of altered consciousness, anatomical defects, or congestion must undergo myringotomy or terminate therapy. Claustrophobia was the second most common adverse effect. Convulsions and tension pneumocephalus were rare.

Perhaps the most concerning risk of HBOT for patients with TBI is the potential waste of human and financial resources.
 

Desperate physicians and patients

As a neurologist who regularly treats patients with TBI, I share the review authors’ frustration regarding the limited efficacy of available treatments. However, the suboptimal efficacy of currently available therapy is insufficient justification to recommend HBOT.

With respect to chronic TBI, it is difficult to imagine how HBOT could reverse brain injury that has been present for months or years. No other therapy exists that reliably encourages neuronal regeneration or prevents the development of posttraumatic epilepsy.

Frank Conidi, MD, a board-certified sports neurologist and headache specialist, shared his thoughts via email. He agrees that HBOT may have a role in TBI, but after reviewing Hadanny and colleagues’ paper, he concluded that there is insufficient evidence for the use of HBOT in all forms of TBI. He would like to see large multicenter, well-designed studies with standardized pressures and duration and a standard definition of the various types of head injury.
 

Ongoing research

There are at least five ongoing trials on HBOT for TBI or postconcussive syndrome, including the well-designed placebo-controlled HOT-POCS study. The latter has a novel placebo gas system that addresses Hadanny and colleagues’ contention that even low-dose HBOT might be effective.

The placebo arm in HOT-POCS mimics the HBO environment but provides only 0.21 ATA of oxygen, the same as room air. The active arm provides 100% oxygen at 2.0 ATA. If patients in both arms improve, the benefit will be caused by a placebo response, not HBOT.
 

Conflict of interest

Another concern with the review is that all three authors are affiliated with Aviv Scientific. This company has an exclusive partnership with the world’s largest hyperbaric medicine and research facility, the Sagol Center at Shamir Medical Center in Be’er Ya’akov, Israel.

This conflict of interest does not a priori invalidate their conclusions. However, official HBOT guidelines from a leading organization like the Undersea and Hyperbaric Medicine Society or the American Academy of Neurology would be preferable.
 

Conclusion

There is an urgent unmet need for more effective treatments for postconcussive syndrome and chronic TBI. Despite tantalizing theoretical mechanisms as to why HBOT might promote brain healing after trauma, its efficacy remains unproven.

The review authors’ recommendations for HBOT seem premature. They are arguably a disservice to the many desperate patients and their families who will be tempted to expend valuable resources of time and money for an appealing but unproven therapy. Appropriately designed placebo-controlled studies such as HOT-POCS will help separate fact from wishful thinking.

Dr. Wilner is associate professor of neurology at University of Tennessee Health Science Center, Memphis. He reported a conflict of interest with Accordant Health Services.

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

A recent review by Hadanny and colleagues recommends hyperbaric oxygen therapy (HBOT) for acute moderate to severe traumatic brain injury (TBI) and selected patients with prolonged postconcussive syndrome.

This article piqued my curiosity because I trained in HBOT more than 20 years ago. As a passionate scuba diver, my motivation was to master treatment for air embolism and decompression illness. Thankfully, these diving accidents are rare. However, I used HBOT for nonhealing wounds, and its efficacy was sometimes remarkable.
 

Paradoxical results with oxygen therapy

Although it may seem self-evident that “more oxygen is better” for medical illness, this is not necessarily true. I recently interviewed Ola Didrik Saugstad, MD, who demonstrated that the traditional practice of resuscitating newborns with 100% oxygen was more toxic than resuscitation with air (which contains 21% oxygen). His counterintuitive discovery led to a lifesaving change in the international newborn resuscitation guidelines.

The Food and Drug Administration has approved HBOT for a wide variety of conditions, but some practitioners enthusiastically promote it for off-label indications. These include antiaging, autism, multiple sclerosis, and the aforementioned TBI.

More than 50 years ago, HBOT was proposed for stroke, another disorder where the brain has been deprived of oxygen. Despite obvious logic, clinical trials have been unconvincing. The FDA has not approved HBOT for stroke.
 

HBOT in practice

During HBOT, the patient breathes 100% oxygen while the whole body is pressurized within a hyperbaric chamber. The chamber’s construction allows pressures above normal sea level of 1.0 atmosphere absolute (ATA). For example, The U.S. Navy Treatment Table for decompression sickness recommends 100% oxygen at 2.8 ATA. Chambers may hold one or more patients at a time.

The frequency of therapy varies but often consists of 20-60 sessions lasting 90-120 minutes. For off-label use like TBI, patients usually pay out of pocket. Given the multiple treatments, costs can add up.
 

Inconsistent evidence and sham controls

The unwieldy 33-page evidence review by Hadanny and colleagues cites multiple studies supporting HBOT for TBI. However, many, if not all, suffer from methodological flaws. These include vague inclusion criteria, lack of a control group, small patient numbers, treatment at different times since injury, poorly defined or varying HBOT protocols, varying outcome measures, and superficial results analysis.

A sham or control arm is essential for HBOT research trials, given the potential placebo effect of placing a human being inside a large, high-tech, sealed tube for an hour or more. In some sham-controlled studies, which consisted of low-pressure oxygen (that is, 1.3 ATA as sham vs. 2.4 ATA as treatment), all groups experienced symptom improvement. The review authors argue that the low-dose HBOT sham arms were biologically active and that the improvements seen mean that both high- and low-dose HBOT is therapeutic. The alternative explanation is that the placebo effect accounted for improvement in both groups.

The late Michael Bennett, a world authority on hyperbaric and underwater medicine, doubted that conventional HBOT sham controls could genuinely have a therapeutic effect, and I agree. The upcoming HOT-POCS trial (discussed below) should answer the question more definitively.
 

Mechanisms of action and safety

Mechanisms of benefit for HBOT include increased oxygen availability and angiogenesis. Animal research suggests that it may reduce secondary cell death from TBI, through stabilization of the blood-brain barrier and inflammation reduction.

HBOT is generally safe and well tolerated. A retrospective analysis of 1.5 million outpatient hyperbaric treatments revealed that less than 1% were associated with adverse events. The most common were ear and sinus barotrauma. Because HBOT uses increased air pressure, patients must equalize their ears and sinuses. Those who cannot because of altered consciousness, anatomical defects, or congestion must undergo myringotomy or terminate therapy. Claustrophobia was the second most common adverse effect. Convulsions and tension pneumocephalus were rare.

Perhaps the most concerning risk of HBOT for patients with TBI is the potential waste of human and financial resources.
 

Desperate physicians and patients

As a neurologist who regularly treats patients with TBI, I share the review authors’ frustration regarding the limited efficacy of available treatments. However, the suboptimal efficacy of currently available therapy is insufficient justification to recommend HBOT.

With respect to chronic TBI, it is difficult to imagine how HBOT could reverse brain injury that has been present for months or years. No other therapy exists that reliably encourages neuronal regeneration or prevents the development of posttraumatic epilepsy.

Frank Conidi, MD, a board-certified sports neurologist and headache specialist, shared his thoughts via email. He agrees that HBOT may have a role in TBI, but after reviewing Hadanny and colleagues’ paper, he concluded that there is insufficient evidence for the use of HBOT in all forms of TBI. He would like to see large multicenter, well-designed studies with standardized pressures and duration and a standard definition of the various types of head injury.
 

Ongoing research

There are at least five ongoing trials on HBOT for TBI or postconcussive syndrome, including the well-designed placebo-controlled HOT-POCS study. The latter has a novel placebo gas system that addresses Hadanny and colleagues’ contention that even low-dose HBOT might be effective.

The placebo arm in HOT-POCS mimics the HBO environment but provides only 0.21 ATA of oxygen, the same as room air. The active arm provides 100% oxygen at 2.0 ATA. If patients in both arms improve, the benefit will be caused by a placebo response, not HBOT.
 

Conflict of interest

Another concern with the review is that all three authors are affiliated with Aviv Scientific. This company has an exclusive partnership with the world’s largest hyperbaric medicine and research facility, the Sagol Center at Shamir Medical Center in Be’er Ya’akov, Israel.

This conflict of interest does not a priori invalidate their conclusions. However, official HBOT guidelines from a leading organization like the Undersea and Hyperbaric Medicine Society or the American Academy of Neurology would be preferable.
 

Conclusion

There is an urgent unmet need for more effective treatments for postconcussive syndrome and chronic TBI. Despite tantalizing theoretical mechanisms as to why HBOT might promote brain healing after trauma, its efficacy remains unproven.

The review authors’ recommendations for HBOT seem premature. They are arguably a disservice to the many desperate patients and their families who will be tempted to expend valuable resources of time and money for an appealing but unproven therapy. Appropriately designed placebo-controlled studies such as HOT-POCS will help separate fact from wishful thinking.

Dr. Wilner is associate professor of neurology at University of Tennessee Health Science Center, Memphis. He reported a conflict of interest with Accordant Health Services.

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

TOPLINE:

Ultrasonography may serve as an alternative to radiography for diagnosing pediatric forearm fractures, thus reducing the number of children undergoing radiography at initial emergency department presentation, as well as their waiting time in ED.

METHODOLOGY:

• After the World Health Organization reported a lack of access to any diagnostic imaging in approximately two-thirds of the world population in 2010, ultrasonography has gained popularity in low- and middle-income countries.
• The initial use of ultrasonography is in accordance with the principle of maintaining radiation levels as low as reasonably achievable.
• The BUCKLED trial was conducted, including 270 pediatric patients (age, 5-15 years) who presented to the ED with isolated, acute, clinically nondeformed distal forearm fractures.
• The participants were randomly assigned to receive initial point-of-care ultrasonography (n = 135) or radiography (n = 135) in the ED.
• The primary outcome was the physical function of the affected arm at 4 weeks evaluated using the Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) tool.

TAKEAWAY:

• At 4 weeks, mean PROMIS scores were 36.4 and 36.3 points in ultrasonography and radiography groups, respectively (mean difference, 0.1 point; 95% confidence interval, − 1.3 to 1.4), indicating noninferiority of ultrasonography over radiography.
• Ultrasonography and radiography groups showed similar efficacy in terms of PROMIS scores at 1 week (MD, 0.7 points; 95% CI, − 1.4 to 2.8) and 8 weeks (MD, 0.1 points; 95% CI, − 0.5 to 0.7).
• Participants in the ultrasonography group had a shorter length of stay in the ED (median difference, 15 minutes; 95% CI, 1-29) and a shorter treatment time (median difference, 28 minutes; 95% CI, 17-40) than those in the radiography group.
• No important fractures were missed with ultrasonography, and no significant difference was observed in the frequency of adverse events or unplanned returns to the ED between the two groups.

IN PRACTICE:

Noting the benefit-risk profile of an ultrasound-first approach in an ED setting, the lead author, Peter J. Snelling, MB, BS, MPH&TM, from Menzies Health Institute Queensland, Gold Coast, Australia, said: “It is highly unlikely that any important fractures would be missed using the protocol that we trained clinicians. The risk is low and the benefit is moderate, such as reducing length of stay and increased level of patient satisfaction.”

He further added that, “with an ultrasound-first approach, clinicians can scan the patient at time of review and may even be able to discharge them immediately (two-thirds of instances in our NEJM trial). This places the patient at the center of care being provided.”
 

SOURCE: 

Authors from the BUCKLED Trial Group published their study in the New England Journal of Medicine.

LIMITATIONS:

PROMIS scores may have been affected by variations in subsequent therapeutic interventions rather than the initial diagnostic method. PROMIS tool was not validated in children younger than 5 years of age.

DISCLOSURES:

The study was funded by the Emergency Medicine Foundation and others. The authors have declared no relevant interests to disclose.

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

TOPLINE:

Ultrasonography may serve as an alternative to radiography for diagnosing pediatric forearm fractures, thus reducing the number of children undergoing radiography at initial emergency department presentation, as well as their waiting time in ED.

METHODOLOGY:

• After the World Health Organization reported a lack of access to any diagnostic imaging in approximately two-thirds of the world population in 2010, ultrasonography has gained popularity in low- and middle-income countries.
• The initial use of ultrasonography is in accordance with the principle of maintaining radiation levels as low as reasonably achievable.
• The BUCKLED trial was conducted, including 270 pediatric patients (age, 5-15 years) who presented to the ED with isolated, acute, clinically nondeformed distal forearm fractures.
• The participants were randomly assigned to receive initial point-of-care ultrasonography (n = 135) or radiography (n = 135) in the ED.
• The primary outcome was the physical function of the affected arm at 4 weeks evaluated using the Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) tool.

TAKEAWAY:

• At 4 weeks, mean PROMIS scores were 36.4 and 36.3 points in ultrasonography and radiography groups, respectively (mean difference, 0.1 point; 95% confidence interval, − 1.3 to 1.4), indicating noninferiority of ultrasonography over radiography.
• Ultrasonography and radiography groups showed similar efficacy in terms of PROMIS scores at 1 week (MD, 0.7 points; 95% CI, − 1.4 to 2.8) and 8 weeks (MD, 0.1 points; 95% CI, − 0.5 to 0.7).
• Participants in the ultrasonography group had a shorter length of stay in the ED (median difference, 15 minutes; 95% CI, 1-29) and a shorter treatment time (median difference, 28 minutes; 95% CI, 17-40) than those in the radiography group.
• No important fractures were missed with ultrasonography, and no significant difference was observed in the frequency of adverse events or unplanned returns to the ED between the two groups.

IN PRACTICE:

Noting the benefit-risk profile of an ultrasound-first approach in an ED setting, the lead author, Peter J. Snelling, MB, BS, MPH&TM, from Menzies Health Institute Queensland, Gold Coast, Australia, said: “It is highly unlikely that any important fractures would be missed using the protocol that we trained clinicians. The risk is low and the benefit is moderate, such as reducing length of stay and increased level of patient satisfaction.”

He further added that, “with an ultrasound-first approach, clinicians can scan the patient at time of review and may even be able to discharge them immediately (two-thirds of instances in our NEJM trial). This places the patient at the center of care being provided.”
 

SOURCE: 

Authors from the BUCKLED Trial Group published their study in the New England Journal of Medicine.

LIMITATIONS:

PROMIS scores may have been affected by variations in subsequent therapeutic interventions rather than the initial diagnostic method. PROMIS tool was not validated in children younger than 5 years of age.

DISCLOSURES:

The study was funded by the Emergency Medicine Foundation and others. The authors have declared no relevant interests to disclose.

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

TOPLINE:

Ultrasonography may serve as an alternative to radiography for diagnosing pediatric forearm fractures, thus reducing the number of children undergoing radiography at initial emergency department presentation, as well as their waiting time in ED.

METHODOLOGY:

• After the World Health Organization reported a lack of access to any diagnostic imaging in approximately two-thirds of the world population in 2010, ultrasonography has gained popularity in low- and middle-income countries.
• The initial use of ultrasonography is in accordance with the principle of maintaining radiation levels as low as reasonably achievable.
• The BUCKLED trial was conducted, including 270 pediatric patients (age, 5-15 years) who presented to the ED with isolated, acute, clinically nondeformed distal forearm fractures.
• The participants were randomly assigned to receive initial point-of-care ultrasonography (n = 135) or radiography (n = 135) in the ED.
• The primary outcome was the physical function of the affected arm at 4 weeks evaluated using the Pediatric Upper Extremity Short Patient-Reported Outcomes Measurement Information System (PROMIS) tool.

TAKEAWAY:

• At 4 weeks, mean PROMIS scores were 36.4 and 36.3 points in ultrasonography and radiography groups, respectively (mean difference, 0.1 point; 95% confidence interval, − 1.3 to 1.4), indicating noninferiority of ultrasonography over radiography.
• Ultrasonography and radiography groups showed similar efficacy in terms of PROMIS scores at 1 week (MD, 0.7 points; 95% CI, − 1.4 to 2.8) and 8 weeks (MD, 0.1 points; 95% CI, − 0.5 to 0.7).
• Participants in the ultrasonography group had a shorter length of stay in the ED (median difference, 15 minutes; 95% CI, 1-29) and a shorter treatment time (median difference, 28 minutes; 95% CI, 17-40) than those in the radiography group.
• No important fractures were missed with ultrasonography, and no significant difference was observed in the frequency of adverse events or unplanned returns to the ED between the two groups.

IN PRACTICE:

Noting the benefit-risk profile of an ultrasound-first approach in an ED setting, the lead author, Peter J. Snelling, MB, BS, MPH&TM, from Menzies Health Institute Queensland, Gold Coast, Australia, said: “It is highly unlikely that any important fractures would be missed using the protocol that we trained clinicians. The risk is low and the benefit is moderate, such as reducing length of stay and increased level of patient satisfaction.”

He further added that, “with an ultrasound-first approach, clinicians can scan the patient at time of review and may even be able to discharge them immediately (two-thirds of instances in our NEJM trial). This places the patient at the center of care being provided.”
 

SOURCE: 

Authors from the BUCKLED Trial Group published their study in the New England Journal of Medicine.

LIMITATIONS:

PROMIS scores may have been affected by variations in subsequent therapeutic interventions rather than the initial diagnostic method. PROMIS tool was not validated in children younger than 5 years of age.

DISCLOSURES:

The study was funded by the Emergency Medicine Foundation and others. The authors have declared no relevant interests to disclose.

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

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Traumatic brain injury (TBI) that occurs in early adulthood is associated with cognitive decline in later life, results from a study of identical twins who served in World War II show.

The research, which included almost 9,000 individuals, showed that twins who had experienced a TBI were more likely to have lower cognitive function at age 70 versus their twin who did not experience a TBI, especially if they had lost consciousness or were older than age 24 at the time of injury. In addition, their cognitive decline occurred at a more rapid rate.

“We know that TBI increases the risk of developing Alzheimer’s disease and other dementias in later life, but we haven’t known about TBI’s effect on cognitive decline that does not quite meet the threshold for dementia,” study investigator Marianne Chanti-Ketterl, PhD, Duke University, Durham, N.C., said in an interview.

“We know that TBI increases the risk of dementia in later life, but we haven’t known if TBI affects cognitive function, causes cognitive decline that has not progressed to the point of severity with Alzheimer’s or dementia,” she added.

Being able to study the impact of TBI in monozygotic twins gives this study a unique strength, she noted.

“The important thing about this is that they are monozygotic twins, and we know they shared a lot of early life exposure, and almost 100% genetics,” Dr. Chanti-Ketterl said.

The study was published online in Neurology.

For the study, the investigators assessed 8,662 participants born between 1917 and 1927 who were part of the National Academy of Sciences National Research Council’s Twin Registry. The registry is composed of male veterans of World War II with a history of TBI, as reported by themselves or a caregiver.

The men were followed up for many years as part of the registry, but cognitive assessment only began in the 1990s. They were followed up at four different time points, at which time the Telephone Interview for Cognitive Status (TICS-m), an alternative to the Mini-Mental State Examination that must be given in person, was administered.

A total of 25% of participants had experienced concussion in their lifetime. Of this cohort, there were 589 pairs of monozygotic twins who were discordant (one twin had TBI and the other had not).

Among the monozygotic twin cohort, a history of any TBI and being older than age 24 at the time of TBI were associated with lower TICS-m scores.

A twin who experienced TBI after age 24 scored 0.59 points lower on the TICS-m at age 70 than his twin with no TBI, and cognitive function declined faster, by 0.05 points per year.
 

First study of its kind

Holly Elser, MD, PhD, MPH, an epidemiologist and resident physician in neurology at the University of Pennsylvania, Philadelphia, and coauthor of an accompanying editorial, said in an interview that the study’s twin design was a definite strength.

“There are lots of papers that have remarked on the apparent association between head injury and subsequent dementia or cognitive decline, but to my knowledge, this is one of the first, if not the first, to use a twin study design, which has the unique advantage of having better control over early life and genetic factors than would ever typically be possible in a dataset of unrelated adults,” said Dr. Elser.

She added that the study findings “strengthen our understanding of the relationship between TBI and later cognitive decline, so I think there is an etiologic value to the study.”

However, Dr. Elser noted that the composition of the study population may limit the extent to which the results apply to contemporary populations.

“This was a population of White male twins born between 1917 and 1927,” she noted. “However, does the experience of people who were in the military generalize to civilian populations? Are twins representative of the general population or are they unique in terms of their risk factors?”

It is always important to emphasize inclusivity in clinical research, and in dementia research in particular, Dr. Elser added.

“There are many examples of instances where racialized and otherwise economically marginalized groups have been excluded from analysis, which is problematic because there are already economically and socially marginalized groups who disproportionately bear the brunt of dementia.

“This is not a criticism of the authors’ work, that their data didn’t include a more diverse patient base, but I think it is an important reminder that we should always interpret study findings within the limitations of the data. It’s a reminder to be thoughtful about taking explicit steps to include more diverse groups in future research,” she said.

The study was funded by the National Institute on Aging/National Institutes of Health and the Department of Defense. Dr. Chanti-Ketterl and Dr. Elser have reported no relevant financial relationships.

A version of this article appeared on Medscape.com.