Category: Injury & Trauma

Categories : Injury & TraumaTags :

Scientists Discover the Body’s Alarm System for Severe Blood Loss

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Red blood cells
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In a discovery that could greatly benefit the treatment of traumatic injuries, scientists have identified a cluster of cells in the brainstem that control the body’s response to severe blood loss

The collection of neurons that the researchers discovered drive a response that maintains blood pressure during blood loss. However, severe blood loss eventually results in cardiovascular collapse, a condition called ‘decompensated haemorrhage’, marked by an abrupt and dangerous loss of blood pressure that presages haemorrhagic shock, where the body’s organs begin to shut down.

“During blood loss, the brain coordinates a cardiovascular response that supports blood flow to critical organs, like the heart and brain,” said researcher George Souza, PhD. “Our study shows that the cardiovascular response to blood loss depends on changes in the activity of a few hundred neurons in the brainstem.”

The new results, published in Cell Reports, shed light on an important process the body uses to maintain its blood pressure. Neurons, termed adrenergic C1 neurons, monitor blood pressure and activate during blood loss, increasing vasodilatory nerve activity that maintains proper blood pressure.

The scientists utilised advanced imaging and a technique called optogenetics controls neurons using light. Their research revealed that the C1 neurons are hyperactive during blood loss, and this keeps blood pressure study. But these neurons become inactive with severe blood loss, resulting in cardiovascular collapse.

The scientists found that re-activating the C1 neurons in lab rats restored both blood pressure and heart rate before cardiovascular collapse could lead to haemorrhagic shock.

“Our study indicates that reactivating the brain pathways controlling blood pressure during decompensated haemorrhage effectively reverses cardiovascular collapse. We think this indicates that neuromodulation of the pathways described by our study could be a beneficial adjunct therapy for low blood pressure following blood loss,” explained lead researcher Stephen Abbott, PhD.

The researchers noted that more research is needed as several factors could also cause the C1 neurons’ drop in activity during the onset of decompensated haemorrhage.

“These findings illuminate the importance of the brain-body interactions during blood loss and provide a new perspective for the underlying cause of cardiovascular collapse,” Dr Abbott said.

Source: University of Virginia Health System

Categories : Immune System Injury & TraumaTags :

Researchers Identify a Key Regulatory Mechanism in Inflammation

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A newly published study has identified a key regulatory mechanism in inflammation that may lead to new targets for resolving that inflammation –and the inflammation of patients with sepsis, cancer and COVID.

In the journal PNAS, scientists reported their discovery of a regulatory pathway for immune response after infection or injury, such as burns. Dysregulation of this pathway could differentiate those who are at risk of fatal sepsis or help identify targets to resolve this unregulated inflammation.

“We are very excited about the findings in this paper and the far-reaching impacts it could have on understanding a key regulatory step in the immune response,” said co-lead author Cindy McReynolds, who holds a doctorate in pharmacology and toxicology.

In a rodent model, the research team found that the metabolites of linoleic acid formed by the enzyme, soluble epoxide hydrolase (sEH), drive damaging inflammation after injury. These metabolites, known as lipid mediators, regulate inflammation, blood pressure and pain. Drugs that inhibit the sEH enzyme and reduce inflammation could lead to better outcomes.

“Our previous work identified that these same lipid mediators were up-regulated in severe COVID infections, and we are now finding that these compounds play a role in modulating the immune response so that the body is unable to fight infection or respond properly to trauma without leading to a potentially fatal overreaction,” said Dr McReynolds.

“This dysregulation has fatal consequences in serious diseases such as COVID, cancer, sepsis, burn, where fatality rates can be as high as 40 percent in severe cases,” she said. “An understanding of these pathways can help identify patients at risk of developing serious disease or identify new therapeutic targets for treatment.”

“The immunological disbalance we see in many cases of severe burn injury, trauma and sepsis pose a huge clinical challenge as we lack the understanding of how to diagnose and treat it,” explained co-lead author Dr Christian Bergmann. “With this work, we reveal an important mechanism how immune cells are functionally disabled by sEH-derived metabolites of linoleic acid.”

“The natural compounds we are studying in this paper are metabolites of linoleic acid (LA), an essential fatty acid the body needs in very small amounts to survive and is only available through the diet,” Dr McReynolds elaborated. “At lower concentrations, these metabolites are necessary for regulating thermogenesis and heart health but promote inflammation at higher concentrations. LA is more stable and much cheaper than longer chain polyunsaturated fatty acids, so heavily processed foods have higher LA content to increase shelf-life. Additionally, agricultural practices, such as feeding animals corn-based diets, have increased LA in meats and dairy products.”

“As a result, we are consuming the highest amount of linoleic acid and have the highest recorded concentration of LA in our fatty tissue in human history,” McReynolds said. “As our bodies respond to stress or disease, we metabolise LA into the regulatory metabolites that were monitored in this paper. At higher concentrations, the immune system was unable to properly respond to infection, thereby promoting a sustained immune response. These observations are important in inflammatory-driven diseases, such as sepsis and COVID, but could also be important in understanding many of the increased chronic diseases we are seeing in our population.”

Source: UC Davis

Categories : Hospitals Injury & TraumaTags :

Amino Acid Supplementation after Fracture Surgery Reduces Complications

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Lower leg bones
Photo by Nino Liverani on Unsplash

By adding conditionally essential amino acids (CEAA) to the diets of patients recovering from fracture fixation surgery, complications are reduced and skeletal muscle wasting is prevented, concludes a study published in The Journal of Bone & Joint Surgery.

The study supports the use of widely available CEAA supplements to promote recovery and preserve function in patients undergoing surgery for repair of major fractures. “Our results suggest that this inexpensive, low-risk intervention has considerable potential to improve outcomes after fracture fixation,” according to the report by Michael Willey, MD, and colleagues of University of Iowa Hospital and Clinics, Iowa City.

The study included 400 patients undergoing operative fixation of fractures in the limbs and/or pelvis at the researchers’ trauma centre. In equal numbers and stratified by fracture severity, patients were randomises to either standard postoperative nutrition or standard nutrition plus CEAA supplementation.

CEAAs are termed “conditionally essential” because the body doesn’t usually require them. However, during times of illness or stress, the need for these conditional amino acids increases dramatically. Previous studies have reported that CEAA supplementation can improve wound-healing and other outcomes in patients with a variety of conditions, including postoperative recovery. In the new trial, patients assigned to the CEAA group received a standard supplement that included arginine, leucine, and glutamine.

At follow-up, the overall complication rate was significantly lower for patients who received CEAA supplementation (30.5%) compared with those who did not receive CEAA (43.8%). The CEAA group also had a lower rate of nonunion (5.1 vs 13.2%, respectively). Some other types of complications, including surgical-site infections, were similar between groups.

Patients who undergo operative fracture fixation are at risk of skeletal muscle wasting, which often results in weight loss as a result of reduced muscle mass. In the new study, patients receiving CEAA supplements had little or no change in fat-free body mass. In contrast, patients receiving standard nutrition had a 1kg reduction in fat-free mass at 6 weeks postoperatively, which took until 12 weeks to return to normal.

An unexpected finding was a sharply reduced mortality rate in the CEAA group (0.5% compared to 4.1 % for the control). Although the authors could not explain the lower risk of death in patients receiving CEAA, they suggest it might result from “unidentified confounding factors.”

Despite advances in surgical techniques, trauma patients undergoing operative fixation of extremity and pelvic fractures remain at risk of complications and prolonged loss of function. “Malnutrition is a potentially modifiable risk factor for mortality, fracture nonunion, wound complications, and increased length of stay,” the authors wrote.

CEAA supplementation therefore appears to be a simple, risk-free, and inexpensive means of promoting good nutrition after fracture fixation surgery. Controlling for other factors, the relative risk of complications is about 40% lower in patients receiving CEAA, with no reduction in fat-free mass during the early weeks of recovery. The researchers concluded: “This study will serve as the foundation for multicentre [randomised controlled trials] that are designed to assess the impact of CEAA nutrition supplementation in reducing complications and loss of functional muscle mass in high-risk populations.”

Source: EurekAlert!

Categories : Injury & TraumaTags :

Platelets Get to Work Right Away on Wound Sites

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Scanning electron microscope image of red blood cells, platelets (green) and T cells (orange). . Image courtesy of Dennis Kunkel, Dennis Kunkel Microscopy, Inc. Part of the exhibit Life:Magnified by ASCB and NIGMS.

New research shows that platelets at a wound site can sense where they are within a blood clot they are and that they can remodel their surroundings accordingly.

Platelets are key to initiating wound healing and the formation of blood clots (thrombus). Fibroblasts are connective tissue cells that are essential for the later stages of wound healing. Fibroblasts invade the clot that has been formed and produce vital proteins, including fibronectin, that then form a structural framework to build the new tissue needed to heal.

This new study, published in Science Advances, indicates that platelets can also form a provisional fibronectin matrix in their surroundings, similar to what fibroblasts do in the later stages of wound healing. This has potential implications for how the integrity of blood clots might be maintained during vascular repair.

Commenting on the discovery, lead author Dr Ingmar Schoen said: “We have identified an additional unexpected role for the most prominent platelet adhesion receptor. Our results show that platelets not only form the clot but also can initiate its remodelling by erecting a fibrous scaffold. This finding challenges some existing paradigms in the field of wound healing, which is dominated by research on fibroblasts.”

The researchers made use of super-resolution microscopy, a powerful imaging technique which enables much finer resolution of structures inside or around cells in vitro. To develop this finding further, in vivo observation of this platelet behaviour will be necessary.

“Without super-resolution microscopy, this discovery would not have been possible,” Dr Schoen noted.

Source: RCSI University

Categories : Injury & TraumaTags :

Over 70% of TBI Patients Report More Symptoms a Year On

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More than 70% of patients with traumatic brain injury (TBI) reported at least one problematic symptom at one year of follow-up that was new or worse than before injury according to a study published in the Journal of Neurotrauma. Half of the patients reported three or more such symptoms after a year.

Joan Machamer, from the University of Washington, Harborview Medical Center, and colleagues representing the TRACK-TBI Investigators, compared the frequency and persistence of symptoms in patients with TBI to two control groups: patients with orthopedic trauma and friend controls. The groups were evaluated at 2 weeks, and 3, 6, and 12 months after injury.

Physical symptoms such as headache, fatigue, and dizziness tended to occur earlier, according to the researchers, with cognitive symptoms becoming dominant later. While physical symptoms declined noticeably over time, cognitive symptoms remained more constant over time.

“Clinicians should inquire about symptoms in patients who have had a TBI, reassure them that experiencing symptoms is common, and direct them to seek treatment for symptoms that are disrupting their lives,” the researchers said.

Commenting on the study, David L. Brody, MD, PhD, Editor-in-Chief of Journal of Neurotrauma noted that is remarkable for several reasons. “First, it is among the largest studies of its type, with over 2,000 participants. Second, it confirms what many of us who practice brain injury medicine have observed for many years– a wide variety of symptoms can be very persistent and very troubling to our patients even after so-called ‘mild’ TBI. Third, the investigators used the right controls; people with orthopedic injury as well as friends of the patients with TBI. Symptoms in patients with TBI were substantially more common and more severe than in both control groups.”

Source: Mary Ann Liebert, Inc.

Categories : Emergency Medicine Injury & TraumaTags :

Injectable Nanoparticles That Could Slow Internal Bleeding

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Photo by Camilo Jimenez on Unsplash

Researchers at MIT have found the ideal size for injectable nanoparticles that could slow traumatic internal bleeding, buying more time for a patient to reach a hospital for further treatment.

In a rat study, the researchers showed that polymer nanoparticles particles in an intermediate size range, (about 150nm in diameter) were the most effective at stopping bleeding. These particles also were much less likely to travel to the lungs or other off-target sites, which larger particles often do. The results were published in ACS Nano.

“With nano systems, there is always some accumulation in the liver and the spleen, but we’d like more of the active system to accumulate at the wound than at these filtration sites in the body,” said senior author Paula Hammond, Professor at MIT.

Nanoparticles that can stop bleeding, also called haemostatic nanoparticles, can be made in a variety of ways. One of the most commonly used strategies is to create nanoparticles made of a biocompatible polymer conjugated with a protein or peptide that attracts platelets, the blood cells that initiate blood clotting.

In this study, the researchers used a polymer known as PEG-PLGA, conjugated with a peptide called GRGDS, to make their particles. Most of the previous studies of polymeric particles to stop bleeding have focused on particles ranging in size from 300–500nm. However, few, if any studies have systematically analysed how size affects the function of the nanoparticles.

“We were really trying to look at how the size of the nanoparticle affects its interactions with the wound, which is an area that hasn’t been explored with the polymer nanoparticles used as haemostats before,” Hong says.

Studies in animals have shown that larger nanoparticles can help to stop bleeding, but those particles also tend to accumulate in the lungs, which can cause unwanted clotting there. In the new study, the MIT team analysed a range of nanoparticles, including small (< 100nm), intermediate (140–220nm), and large (500–650nm).

They first analysed the nanoparticles in the lab to see how how they interacted with platelets in various conditions, to see how well platelets bound to them. They found that, flowing through a tube, the smallest particles bound best to platelets, while the largest particles stuck best to surfaces coated with platelets. However, in terms of the ratio particles to platelets, the intermediate-sized particles were the lowest.

“If you attract a bunch of nanoparticles and they end up blocking platelet binding because they clump onto each other, that is not very useful. We want platelets to come in,” said lead author, Celestine Hong, an MIT graduate student. “When we did that experiment, we found that the intermediate particle size was the one that ended up with the greatest platelet content.”

The researchers injected the different size classes of nanoparticles into mice to see how long they would circulate for, and where they would end up in the body. As with previous studies, the largest nanoparticles tended accumulated in the lungs or other off-target sites.

The researchers then used a rat model of internal injury to study which particles would be most effective at stopping bleeding. They found that the intermediate-sized particles appeared to work the best, and that those particles also showed the greatest accumulation rate at the wound site.

“This study suggests that the bigger nanoparticles are not necessarily the system that we want to focus on, and I think that was not clear from the previous work. Being able to turn our attention to this medium-size range can open up some new doors,” Prof Hammond said.

The researchers now hope to test these intermediate-sized particles in larger animal models, to get more information on their safety and the most effective doses. They hope that eventually, such particles could be used as a first line of treatment to stop bleeding from traumatic injuries long enough for a patient to reach the hospital.

Source: Massachusetts Institute of Technology

Categories : Injury & Trauma Pain ManagementTags :

Chronic Pain in Spinal Cord Injury Increases Mental Health Risk

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Having a spinal cord injury increases risk of developing mental health conditions such as depression and anxiety by nearly 80% compared to those without the traumatic injury, a new study shows. However, chronic pain may have an equally large, negative effect on mental health.

The study, published in Spinal Cord, compared private insurance claims from more than 9000 adults with a traumatic spinal cord injury with those of more than 1 million without. Researchers accounted for a range of psychological conditions, from anxiety and mood disorders to insomnia and dementia.

People living with a spinal cord injury had a diagnosis of a mental health condition more often than those without – 59.1% versus 30.9%. While depression and adverse mental health effects are not inevitable consequences of every traumatic spinal injury, previous studies have consistently echoed higher levels of psychological morbidity among this group than the general population without spinal cord injuries.

However, this study found that chronic centralised and neuropathic pain among adults living with a spinal cord injury were robustly associated with post-traumatic stress disorder, substance use disorders and other mental health conditions. In most cases, chronic pain was an even greater influence on these conditions than exposure to living with the injury itself.

The study authors said the findings should prompt physicians to identify mental health conditions when seeing patients with spinal cord injuries and refer them for treatment.

“Improved clinical efforts are needed to facilitate screening of, and early treatment for, both chronic pain and psychological health in this higher-risk population,” said lead author Dr Mark Peterson, associate professor of physical medicine and rehabilitation at Michigan Medicine.

However, researchers note a lack of insurance coverage and limited available services will likely cause the issue to remain largely unaddressed.

“Stakeholders need to work together to lobby for more federal research funding and special policy amendments to ensure adequate and long-term insurance coverage for both physical and mental health to meet the needs of folks living with spinal cord injuries,” Dr Peterson said.

Source: EurekAlert!

Categories : Injury & TraumaTags :

K-Wires for Wrist Fractures on Par with Cast

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Using metal K-wires (aka ‘pins’) to hold broken wrist bones in place while they heal are no better than a traditional moulded plaster cast, finds a study published by The BMJ.

If the bone fragments in wrist fractures have displaced, they often require manipulation followed either by surgery to insert metal wires or plates, or a moulded cast as a non-surgical alternative, to hold the bones in place while they heal.

Surgery is expensive and carries risk for the patient, whereas a moulded plaster cast is cheaper but may not provide the same functional outcome.

To see which option is superior, researchers tracked the progress of 500 adults, average age of 60 and 83% female. with a displaced wrist fracture. Patients were randomly allocated to receive a cast (255) or surgical fixation with K-wires (245) after manipulation of their fracture. The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months, which included questions about pain, function and disability, and gave an overall score from 0 (best) to 100 (worst).

Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for later surgery.

Of the 79% of patients who completed the follow-up, no statistically significant difference was seen in the PRWE score at three, six or 12 months (average score 21.2 in the cast group compared with 20.7 in the K-wire group). Quality of life was similar.

However, one in eight patients with cast needed later surgery for loss of fracture position in the first six weeks after their injury compared with only one patient in the K-wire group.

Other complications were rare, with no evidence of a difference between the two groups (28 in the cast group compared with 22 in the K-wire group).

Limitations included the fact that neither the treating clinicians nor the participants could be blind to the interventions. Still, the researchers noted this was a large trial involving adults of all ages and the results are based on validated patient reported outcomes, reflecting the care provided across a healthcare system.

As such, they conclude: “Surgical fixation with K-wires did not provide better wrist function at 12 months compared with a moulded cast, indicating that a cast is an acceptable first line treatment following manipulation of a dorsally displaced fracture of the distal radius.”

They added: “Cast treatment avoids the expense and risks of surgical fixation for seven out of eight patients. However, careful follow-up is needed as one in eight patients treated with a cast required subsequent surgical intervention as the fracture reduction could not be maintained.”

Source: The BMJ

Categories : Injury & Trauma NeurologyTags :

Study Uncovers Mechanism Behind Visual Impairment in Traumatic Brain Injury

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A healthy neuron.
A healthy neuron. Credit: NIH

Traumatic brain injury can lead to long-term visual impairment, which researchers have found is caused by a dramatic drop in the number of neurons in the visual cortex. Their findings were published in Communications Biology.

Traumatic brain injury (TBI) is associated with mechanical brain damage and a wide range of neuronal abnormalities.  Injuries to the posterior occipital cortex are common in humans, and can result in visual impairment. Up to 75% of current or former soldiers live with permanent visual dysfunction or cortical blindness. 

The human brain possesses surprising neuroplasticity, which allows other areas of the brain to take over the functions of a damaged area.

Such neuroplasticity is also characteristic of the sensory areas of the visual cortex, which is final component of the visual pathway, responsible for receiving and processing visual impressions. The primary visual cortex (V1) is reached by the nerve fibres of the optic radiation, which carry nerve impulses from the retinas of both eyes.

Until now, scientists knew little about the effects of TBI on long-term visual circuit function. Using mice, a team of researchers examined how neurons respond to visual stimuli two weeks and three months after mild injury to the primary visual cortex (V1). V1 neurons normally show sensitivity to different features of a visual stimulus, such as colour or direction of movement. The preprocessed data is transmitted to subsequent areas of the visual cortex. This study showed that although the primary visual cortex remained largely intact after the brain injury, there was a 35% reduction in the number of neurons. This loss largely affected inhibitory neurons rather than excitatory neurons, which inhibit or stimulate action in the target cells, respectively.

After TBI, fewer than half of the isolated neurons were sensitive to visual stimuli (32% at two weeks after injury; 49% at three months after the event), compared with 90% of V1 cells in the control group. Up to a threefold decrease in neuronal activity was seen after the brain injury, and the cells themselves had worse spatial orientation. The overall results mean that even minor, superficial brain injuries cause long-term impairment in the way visual stimuli are perceived, persisting several months after the event.

Such a deeper understanding of the functional impairments in damaged visual cortex could provide a basis for developing circuit-level therapies for visual cortex damage.

Source: Institute of Physical Chemistry of the Polish Academy of Sciences

Categories : Diseases, Syndromes and Conditions Injury & TraumaTags :

A New Treatment for Chronic Tendon Disease

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Photo by Nino Liverani on Unsplash

The Achilles tendon can endure a load nearly 8 times body weight during exercise, rendering it vulnerable to injury despite its strength, which can be worsened by a failure to properly heal, forming bone instead of new tendon. A new study found that by inhibiting blood vessel formation, the anomalous bone growth can be prevented.

Due to the unique nature of tendons, failing to consult a doctor soon after an injury can lead to chronic tendon disease, which is characterised by pain, swelling, and movement problems. Tendon heterotopic ossification (HO) is a rare type of chronic tendon disease where new bone grows the tendon, causing even more damage. Famous athletes have had to retire early from sports due to a lack of a radical solution for Achilles tendon injuries.

Using single-cell sequencing technology, a team led by Professor Ouyang Hongwei found that changes in the tissue microenvironment of tendon HO alterations in gene expression and in tendon stem progenitor cells. These findings were published in Bone Research, providing a novel treatment for tendon heterotopic ossification.

The researchers firstly found that the tendon specific transcription factor MKX decreased significantly in heterotopic ossified human tendon, and deletion of MKX led to spontaneous ossification of mouse tendon, suggesting that MKX plays a critical role in tendon HO.

Further studies revealed that MKX knockout mouse tendon cells expressed high levels of genes related to blood vessel formation, resulting in vascular invasion and remodelling of the tendon extracellular matrix. This also resulted in abnormal activation of genes related to bone and cartilage in tendon stem cells. These data indicated that inhibition of blood vessel formation may improve the tendon tissue microenvironment and prevent HO progression.

Armed with this knowledge, Prof Ouyang and his colleagues searched for drugs that can inhibit the angiogenesis process. They found that local injection of a small molecule inhibitor known as BIBF1120 significantly inhibited the neovascularisation of tendon after injury, thus alleviating the progression of tendon HO.

Source: MedicalXpress