Category: Injury & Trauma

Categories : Injury & TraumaTags :

Shining a New Light on Tranexamic Acid for Trauma Care

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A new study from Australia, New Zealand and Germany published in the New England Journal of Medicine raises important questions about the success or otherwise of using tranexamic acid in trauma. 

Tranexamic acid is commonly used to limit bleeding during surgery. However, its usefulness in emergency settings as a pre-emptive strike in life-threatening bleeding has been controversial, and recent studies have provided contradictory results about whether or not it saves lives or causes dangerous blood clotting. 

The Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage (PATCH-Trauma) Study was designed to solve this dilemma. Led by Monash University and the Australian and New Zealand Intensive Care Society Clinical Trials Group, it is one of the largest clinical trials ever conducted where treatment was given at the roadside, in an ambulance or in a helicopter prior to reaching hospital. 

It involved 1310 severely injured patients treated by 15 ambulance services and 21 trauma centres in Australia, New Zealand and Germany, taking eight years to complete. 

In addition to all the usual care, patients were randomly assigned to receive pre-hospital tranexamic acid or an inactive placebo. The results showed that for every 100 patients allocated to receive tranexamic acid, there were approximately four extra survivors at six months, but all were severely-disabled and highly-dependent on carers. 

The lead investigator, Professor Russell Gruen, now Dean of the College of Health and Medicine at the Australian National University, described this as a landmark study in trauma care. “It shows it’s not enough to find out only whether treatments save lives or not – quality of life and the long-term outcomes of care also matter,” Professor Gruen said.

Monash University Professor Stephen Bernard, Medical Advisor to Ambulance Victoria and lead for the Australian arm of the study, praised the ambulance services involved. “The PATCH-Trauma Study is further proof that ambulance professionals can conduct rigorous clinical trials in very sick patients and in extremely challenging circumstances,” he said. 

As to whether tranexamic acid should be used for trauma patients, Professor Gruen is circumspect. “Because the drug needs to be given before severely injured patients can make an informed decision, further work is needed to see if we can identify patients who are more likely to survive with a favourable functional outcome if they are given tranexamic acid,” he said. “However, the PATCH-Trauma Study gives us confidence that critical care is possible well before patients get to hospital.” 

Source: EurekAlert!

Categories : Injury & TraumaTags :

Sports Concussions Increase the Risk of Being Re-injured

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Photo by John Torcasio on Unsplash

Concussions are commonplace in contact sports at junior and senior levels. Now, the investigators of a study published in the Journal of Science and Medicine in Sport are suggesting extended recovery times may be needed for youth athletes suffering from head trauma. The new research shows a concussion can increase future injury risk by 50%.

The world-first study from the University of South Australia tracked and evaluated the long-term impact of concussion and subsequent injury risk of 1455 sub-elite junior Australian rules football players.

This builds on previous UniSA research that found an approximate 1.5-fold increased risk of injury of sub-elite Australian rules football players returning from an injury, compared to those with no injury.

Tracking injuries over a seven-season period, researchers found that football players who suffered a concussion were also about 1.5 times more likely to be reinjured in the future when compared to players who had never been injured. This increased risk was the same as players returning from upper and lower limb injuries.

The finding comes ahead of the Australian Senate’s report into concussion injuries, and follows the AFL’s announcement for a $25 million study into the long-term effects of concussions and head knocks.

In the AFL, concussions are one of the most common injuries, with an average of six concussions every 1000 hours played, which involve around 70 to 80 male players every year.

In junior elite football as well as AFL and AFLW, the guidelines for concussion say that the earliest a player can return to play post-concussion is 12 days after the injury, after following the graded progression through a return-to-play program.

Lead researcher, UniSA’s Dr Hunter Bennett, says the significant and elevated risk of injury after a concussion may suggest a longer recovery time is required for some players to better recover before returning to play.

“The current recommendation of 12 days post-concussion may not be sufficient to allow full recovery in elite under-18 footballers,” Dr Bennett says.

It may also indicate that the physical qualities impacted by concussion should be assessed more thoroughly before an athlete is cleared to return to the sport.

“Concussion is a common injury in Australian rules football that can lead to impairments in balance, coordination, reaction time, and decision making – and these impairments can increase the risk of other injuries if an athlete returns to play before being fully recovered.”

A recent consensus statement on concussion in sport also indicates that children and teenagers may take up to four-weeks to recover from a sport related concussion.

“Concussions are a unique injury that occur without muscle tissue damage, instead impacting aspects of motor control,” Dr Bennett says.

“Recurrent injuries can significantly impact team success, player health, and career longevity.

“In elite sports, there is the potential for young athletes to overplay their readiness to return to sport after an injury, as they worry that missing games can exclude them from senior drafting or competition.

“When we know that athletes have a greater risk of another injury post a concussion, it suggests we need unique and careful rehabilitation strategies to monitor when an athlete is fully recovered and ready to return to play.”

Researchers say that future research should seek to identify optimal rehabilitation and injury prevention strategies for athletes who suffer from concussions.

Source: University of South Australia

Categories : Injury & TraumaTags :

Experts Revise Consensus Statement on Management of Concussion in Sport

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Source: CC0

Latest Consensus Statement on Concussion in Sport includes:

  • New and updated age appropriate tools to aid identification and management of condition
  • New versions of return to active sport and education strategies
  • Stronger evidence for benefits of light intensity exercise within first 48 hours to aid recovery
  • New targeted approach to rehabilitation
  • Call for interdisciplinary working group to guide research into potential long term effects

A group of more than 100 expert researchers and clinicians from around the world, co-chaired by Professor Jon Patricios of Wits Sport and Health (WiSH), University of the Witwatersrand (Wits University), has distilled and synthesised new scientific evidence and updated existing recommendations with the aim of optimising the care of athletes at all levels of participation who have, or who are at risk of, concussion.

Based on the outcomes from the International Conference on Concussion in Sport, held in Amsterdam in October 2022, and published in the British Journal of Sports Medicine (BJSM), the Statement is informed by 10 systematic reviews and methodology outlining the new consensus process. The entire process more than 4 years to complete. 

In a bid to be more transparent and inclusive than in previous years, the process adopted anonymous voting, alternative viewpoints, open declarations of potential conflicts of interest, and included the views of athletes, a focus on para-athletes, and ethical perspectives.  

The Statement includes a series of new (SCOAT6, Child SCOAT6) and updated (CRT6, SCAT6, Child SCAT6) age-appropriate tools for clinicians and sports organisations to help them better identify and manage sports related concussion in the short and longer term.

It features new evidence-based strategies for returning to active sport and education after concussion; early exercise and treatment recommendations; approaches to prevention; targeted rehabilitation; and a call for a working group to be set up to guide further research on the potential long term effects of concussion on health. 

Among the key recommendations:

Prevention

  • Policy or rule changes to minimise collisions, such as disallowing body checking in ice hockey – a defensive move in which the player tries to separate the puck from his/her opponent 
  • Neuromuscular training – aerobic, balance, strength, agility exercises +/-neck-specific components – in warm ups 
  • Mouthguard use in ice hockey (all ages)
  • Implementing laws and protocols, such as mandatory removal from play after actual or suspected concussion; healthcare professional clearance to return to play; and education of coaches, parents, and athletes on the signs and symptoms of concussion

Early interventions

  • Strict rest isn’t recommended. There’s now stronger evidence that light intensity physical activity, such as routine activities of daily living, and aerobic exercise, such as walking and stationary cycling, can aid recovery, as can limiting screen time during the first 48 hours.

Rehabilitation

  • For those experiencing dizziness, neck pain and/or headaches for more than 10 days, the Statement recommends cervico-vestibular rehabilitation – physiotherapy exercises to reduce symptoms and improve function.
  • Rehabilitation should be targeted to the needs of the individual.

Persisting symptoms 

  • Multidisciplinary team assessment to identify the types, pattern, and severity of symptoms and any other contributory factors is advised for those with symptoms lasting more than 4 weeks. 

Recovery

  • Advanced neuroimaging, biomarkers (chemical signals from nerves or blood vessels), genetic tests, and other emerging technologies to assess recovery are useful for research into the diagnosis, outlook, and recovery from sports related concussion. But as yet, they are some way off from being used in clinical practice, says the Statement.

Return to education and sport

  • Academic support may be needed for some athletes in the form of a return to learn strategy: this can include modified school attendance, limiting screen time, avoiding any contact sports or game play, extra time to complete assignments/homework or tests.
  • Light intensity activity in the early phases of the return to sport strategy is now recommended, with full sports participation usually occurring within 1 month of injury.
  • But it’s best to manage athletes on an individual basis, accounting for specific factors that may affect their recovery, such as a history of migraine, anxiety, and social factors.

Potential long term effects

  • The Statement notes the “increasing societal concern about possible problems with later in life brain health in former athletes, such as mental health problems, cognitive impairment and neurological diseases.”
  • Studies tracking the mental health of people over time (cohort studies) have found that former amateur and professional athletes don’t seem to be at heightened risk of depression or suicidality later in life.
  • Similarly, no heightened risk of neurological disease has been reported in former amateur athletes in these types of study. But some studies of former professional athletes have reported an association between playing professional American football and professional soccer and neurological disease in later life.
  • But the studies to date on the links between early sports participation and later life dementia and neurological disease are limited because they haven’t been able to adjust for a range of potentially highly influential factors, says the Statement.
  • It recommends setting up an interdisciplinary working group to guide appropriate research into the potential long term effects of concussion on health.

Evidence gaps still to be filled

  • There’s limited evidence on the management of sports related concussion in 5-12 year olds and in para sport athletes, who are known to be at heightened risk of sports related concussion.
  • And little research on concussion exists for certain regions of the world, diverse cultural contexts, sex and genders.

Commenting on the Statement, Consensus Statement co-chair, Dr Kathryn Schneider of the University of Calgary, Canada, says: “This Statement sets out a range of new evidence-based recommendations, including those for concussion prevention as well as new versions of the concussion assessment tools and return to sport and school/learning strategies”. 

“We encourage clinicians and sports organisations around the globe to adapt these recommendations to their own geographic and cultural environments to optimise the care of athletes who have sustained, or who are at risk of, concussion,” she adds.

“The differentiating aspects of this latest Concussion Consensus are the rigorous methodological process we adopted, the new generation of tools available to clinicians, and the emphasis on the positive impact of exercise and targeted rehabilitation as effective interventions,” explains Consensus Statement co-chair, Professor Jon Patricios of Wits University, Johannesburg, South Africa.

“These have the potential to positively change the management of sport-related concussion.”

Source: Wits University

Categories : Injury & TraumaTags :

Could A Perfume Ingredient Stop Coagulopathy in Massive Bleeding?

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The chances of surviving massive blood loss from a traumatic injury such as a gunshot wound are around 50%. To survive, a patient urgently needs a large infusion of blood and coagulation at the wound to stop the bleeding.

The problem is one of these solutions prevents the other. Introducing a large amount of blood to those suffering a massive haemorrhage impairs the blood’s ability to clot, a condition known as coagulopathy.  

Now, Tulane University researchers have uncovered the cause of coagulopathy in trauma victims receiving a blood infusion. They also found that a synthetic compound called dimethyl malonate – often used in perfume manufacturing – has the potential to stop coagulopathy during a massive hemorrhage. The researchers’ findings are part of a new study published in Science Advances.

“Coagulopathy of trauma is a major contributor to mortality, but no treatment has shown to be fully effective,” said Olan Jackson-Weaver, PhD, assistant professor of surgery at Tulane University School of Medicine and corresponding author on the study. “We were getting 60 percent mortality with our animal model. With dimethyl malonate, we got zero percent mortality, and the coagulopathy completely went away.”

Recent studies have shown that coagulopathy during massive haemorrhage treatment is most likely caused by the shedding of the glycocalyx, a barrier of sugars that surrounds and protects cells. In blood vessels, the glycocalyx lines the vessel walls and prevents blood from clotting. However, this is the first study to identify the cellular events that cause the glycocalyx to be ripped apart.

The study found that a large infusion of blood creates a spike in cellular metabolism which causes a change in structure to the cell membrane. This exposes the glycocalyx, allowing it to be chewed up by enzymes and mixed into the bloodstream, where it prevents clotting.

“People have been trying to figure out ways to move the needle a little bit on the death rate from massive haemorrhage for the last 20 or so years and nothing has really worked,” Jackson-Weaver said. “We’re hopeful that understanding these cellular-level events can help to develop something that actually does make a big difference.”

In animal models, dimethyl malonate was effective at inhibiting excessive cellular metabolism, which prevented the glycocalyx from shedding and causing coagulopathy.

But Jackson-Weaver said more research needs to be done to determine if dimethyl malonate is safe for humans or if an equivalent drug that targets cellular metabolism can be developed.

“We’ve established this pathway that causes coagulopathy, so if we can target it therapeutically with a pre-hospital drug or injection, we can hopefully save some lives,” Jackson-Weaver said.

Source: Tulane University

Categories : Diseases, Syndromes and Conditions Injury & TraumaTags :

Autistic Adults Have Higher Risks of Injury and Disease

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A large-scale registry study found that older autistic adults have a significantly higher risk of injury, especially self-inflicted, and physical conditions such as type 2 diabetes, anaemia, heart failure and COPD. The findings were published in The Lancet Healthy Longevity.

“We found an increased disease burden in middle-aged and older autistic adults, both men and women, irrespective of the presence of intellectual disability,” says Shengxin Liu, doctoral student at Karolinska Institutet. “Our findings point up the need to improve the support and care of older autistic adults.”

In the population-based study, the KI researchers linked different national registers and compared the risk for five types of injury and 39 age-related physical conditions in people over the age of 45. Of the four million-plus people born between 1932 and 1967, 1930 women and 3361 men had an autism diagnosis. For each physical condition, they evaluated the 25-year cumulative incidence and the relative risk in autistic people compared with non-autistic people of the same sex and age.

Seven-fold risk of self-harm

Autistic people had a higher risk of four of five studied injures, for which self-harm accounted for the greatest risk increase, followed by poisoning, falls and other physical injuries.

“The risk of self-harm was worryingly high, a full seven times higher than in non-autistic people,” says Liu. “Reasons behind this remain largely unknown. One possible contributing factor could be mental health conditions that commonly co-occur with autism, such as anxiety and depression.”

The researchers also found a risk increase for 15 physical conditions. For example, autistic people had three times the risk of anaemia and glucose dysregulation and almost double the risk of heart failure, type 2 diabetes, and COPD (chronic obstructive pulmonary disease).

Multiple contributory factors

“We now need to find out the cause of these associations and how they are affected by factors such as biology, age when diagnosed with autism, psychotropic treatment and psychosocial environment,” says the study’s last author Mark Taylor, senior researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “But most importantly, researchers, health services and policymakers need to cooperate to make sure that older autistic adults have a better quality of life.”

Since this was an observational study, no causal relationships can be ascertained, and the researchers were not able to take into account variables such as socioeconomic status. Furthermore, given that the study used Swedish registers, it is difficult to make generalisations to other countries.

Source: Karolinska Institutet

Categories : Injury & Trauma PaediatricsTags :

Portable Ultrasound Works Just as Well in Diagnosing Forearm Fractures in Kids

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Portable ultrasound devices could provide an alternative to x-ray machines for diagnosing forearm fractures in children, which could alleviate waiting times for families in hospital emergency departments (ED).

Griffith University researchers Professor Robert Ware and Senior Lecturer Peter Snelling compared functional outcomes in children given an ultrasound and those who received an x-ray on a suspected distal forearm fracture. Dr Snelling said the ultrasounds were performed by nurses, physiotherapists and emergency physicians at four south-east Queensland hospitals.

“They treated 270 children, aged between five and 15 years, during the randomised trial, which included a check-up 28 days later and another check-in at eight weeks,” Dr Snelling said. “The findings show the majority of children had similar recoveries and returned to full physical function.”

Less than one-third of children who were given an ultrasound needed a follow-up x-ray and care at an orthopaedic clinic. Those who didn’t have a buckle fracture or fractured arm were discharged from hospital without the need for further imaging.

Professor Ware said children who had an ultrasound initially had fewer x-rays, and shorter stays in the ED. “Families were also more satisfied with the treatment they received,” he said. “The results are promising and have wider implications beyond in hospital diagnosis and follow up care.

“By using a bedside ultrasound, this frees up the x-ray machine for patients who really need it and can potentially be a cost-cutting measure for hospitals as they reduce the number of x-rays without comprising the safety of patients.

“It also would be extremely beneficial in rural or remote areas eliminating the need for children and their families to travel to a larger hospital for an x-ray.”

Source: Griffith University

Categories : Injury & Trauma New Compounds and TreatmentsTags :

New Compound Secreted by Bacteria Speeds up Healing

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Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. A new study published in eClinical Medicine shows that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

Previously, the researchers had demonstrated accelerated wound healing after topical treatment using lactic acid bacteria (Limosilactobacillus reuteri) genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

Now, in their first clinical study on humans, the researchers established safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

The results show that treatment using ILP100-Topical was safe and well tolerated among all individuals and doses, and neither ILP100 nor CXCL12 could be detected in locations beyond the wounds. A significantly higher proportion of healed wounds (p=0.020) was seen on day 32 using multi-dose ILP100-Topical compared to saline and placebo (76% (73/96) and 59% (57/96) healed wounds respectively) when the results from the multi-dose-treated wounds were pooled. In addition, the time to first recorded healing was reduced by an average of 6 days, and by 10 days at the highest dose. The mechanism of action of ILP100-Topical was also confirmed when the treatment resulted in increased CXCL12-positive cells in the wounds, as well as increased blood flow around the wounds during the healing phase.

“Our study shows that bacteria modified to produce and deliver human protein for local effects can be used as drugs to accelerate the healing of wounds. This is the first time this has been shown in controlled human studies, and it can be expected that the effect is greater in patients with diseases that negatively affect wound healing,” explains Mia Phillipson, Professor at the Department of Medical Cell Biology at Uppsala University.

The favourable safety profile and the beneficial effects on wound healing observed here support further clinical development of ILP100-Topical for the treatment of complex and hard-to-heal wounds in patients, which is already under way.

Many immune-active proteins are inherently unstable and degrade quickly, so supplying them from lactic acid bacteria to the exact site of action is one way to develop them as drugs.

“The potential is really endless when you consider how important a role proteins play in various processes in the body, and how many diseases we currently do not have good enough treatments for. We have already produced another drug candidate to cure and reduce inflammation in the gut of cancer patients – ILP100-Oral – and in the future we will start a research project with another chemokine for the treatment of lung diseases,” concludes Phillipson.

Source: Uppsala University

Categories : Injury & Trauma NeurologyTags :

Up to Half of Concussions May Have Long-lasting Effects

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Even mild concussion can cause long-lasting effects to the brain, according to a University of Cambridge analysis published in Brain. The study researchers showed that for almost a half of all people who receive a concussion, there are changes in how regions of the brain communicate with each other. This could potential cause long term symptoms such as fatigue and cognitive impairment.

Concussion, a mild traumatic brain injury, can occur as a result of a fall, a sports injury or from a cycling accident or car crash, for example. But despite the ‘mild’ label, it is commonly linked with persistent symptoms and incomplete recovery. Such symptoms include depression, cognitive impairment, headaches, and fatigue.

While some clinicians in recent studies predict that 9 out of 10 individuals who experience concussion will have a full recovery after six months, evidence is emerging that only a half achieve a full recovery. This means that a significant proportion of patients may not receive adequate post-injury care.

Predicting which patients will have a fast recovery and who will take longer to recover is challenging, however. At present, patients with suspected concussion will typically receive either a CT or MRI brain scan to look for structural problems, such as inflammation or bruising. Yet even if these scans show no obvious structural damage, a patient’s symptoms may still persist.

Dr Emmanuel Stamatakis from the Department of Clinical Neurosciences and Division of Anaesthesia at the University of Cambridge said: “Worldwide, we’re seeing an increase in the number of cases of mild traumatic brain injury, particularly from falls in our ageing population and rising numbers of road traffic collisions in low- and middle-income countries.

“At present, we have no clear way of working out which of these patients will have a speedy recovery and which will take longer, and the combination of over-optimistic and imprecise prognoses means that some patients risk not receiving adequate care for their symptoms.”

Dr Stamatakis and colleagues studied functional MRI (fMRI) brain scans taken from 108 patients with mild traumatic brain injury and compared them with scans from 76 healthy volunteers. Patients were also assessed for ongoing symptoms.

The patients and volunteers had been recruited to CENTER-TBI, a large European research project which aims to improve the care for patients with traumatic brain injury.

The team found that just under half (45%) were still showing symptoms resulting from their brain injury, with the most common being fatigue, poor concentration and headaches.

The researchers found that these patients had abnormalities in a region of the brain known as the thalamus, which integrates all sensory information and relays this information around the brain. Counter-intuitively, concussion was associated with increased connectivity between the thalamus and the rest of the brain – in other words, the thalamus was trying to communicate more as a result of the injury – and the greater this connectivity, the poorer the prognosis for the patient.

Rebecca Woodrow, a PhD student in the Department of Clinical Neuroscience and Hughes Hall, Cambridge, said: “Despite there being no obvious structural damage to the brain in routine scans, we saw clear evidence that the thalamus – the brain’s relay system – was hyperconnected. We might interpret this as the thalamus trying to over-compensate for any anticipated damage, and this appears to be at the root of some of the long-lasting symptoms that patients experience.”

Using positron emission tomography (PET) scans, the researchers were able to make associations with key neurotransmitters depending on which long-term symptoms a patient displayed. For example, patients experiencing cognitive problems such as memory difficulties showed increased connectivity between the thalamus and areas of the brain rich in the neurotransmitter noradrenaline; patients experiencing emotional symptoms, such as depression or irritability, showed greater connectivity with areas of the brain rich in serotonin.

Dr Stamatakis added: “We know that there already drugs that target these brain chemicals so our findings offer hope that in future, not only might we be able to predict a patient’s prognosis, but we may also be able to offer a treatment targeting their particular symptoms.”

Source: University of Cambridge

Categories : Ageing Injury & TraumaTags :

Researchers Develop 5-factor Model for Nursing Home Fall Risks

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Carers help an old man to walk
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In research published in the Journal of the American Geriatrics Society, investigators developed and validated models that can predict the risk of fall-related injuries (FRI) in nursing home residents based on routinely collected clinical data.

The researchers conducted retrospective cohort study of long-stay US nursing home residents (mean age 85 years, 69.6% female) between January 1, 2016 and December 31, 2017 (n = 733 427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through statistical methods, from an original set of 70 predictors. To come up with a useful clinical tool, they calculated a score using the five strongest predictors in the model.

Within 2 years of follow-up, 6% of residents experienced one or more FRI. The prediction models achieved good discrimination and excellent calibration for accurately estimating individuals’ six-month and two-year risk of fall-related injuries. In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14–2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94–2.12). Performance results were similar in the validation sample.

“These models can be used by researchers and clinicians to accurately determine patient risk for fall-related injuries using routinely collected clinical assessment data,” the authors wrote. “In nursing homes, these models should be used to target preventive strategies.”

Source: Wiley

Categories : Cancer Injury & TraumaTags :

A Link Between Head Injury and Increased Glioma Risk

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Previous research has hinted at a possible link between head injury and increased rates of gliomas, rare but aggressive brain tumours. A University College London team has now identified a possible mechanism to explain this link, implicating genetic mutations acting in concert with brain tissue inflammation to change the behaviour of cells, making them more likely to become cancerous.

Publishing in Current Biology, the researchers have now identified a possible mechanism to explain this link, implicating genetic mutations acting in concert with brain tissue inflammation to change the behaviour of cells, making them more likely to become cancerous. Although this study was largely carried out in mice, it suggests that it would be important to explore the relevance of these findings to human gliomas.

The study was led by Professor Simona Parrinello (UCL Cancer Institute), Head of the Samantha Dickson Brain Cancer Unit and co-lead of the Cancer Research UK Brain Tumour Centre of Excellence. She said: “Our research suggests that a brain trauma may contribute to an increased risk of developing brain cancer in later life.”

Gliomas are brain tumours that often arise in neural stem cells. More mature types of brain cells, such as astrocytes, have been considered less likely to give rise to tumours. However, recent findings have demonstrated that after injury, astrocytes can exhibit stem cell behaviour again.

Professor Parrinello and her team therefore set out to investigate whether this property may make astrocytes able to form a tumour following brain trauma using a pre-clinical mouse model.

Young adult mice with brain injury were injected with a substance which permanently labelled astrocytes in red and knocked out the function of the p53 gene, known to have a vital role in suppressing many different cancers. A control group was treated the same way, but the p53 gene was left intact. A second group of mice was subjected to p53 inactivation in the absence of injury.

Professor Parrinello said: “Normally astrocytes are highly branched – they take their name from stars – but what we found was that without p53 and only after an injury the astrocytes had retracted their branches and become more rounded. They weren’t quite stem cell-like, but something had changed. So we let the mice age, then looked at the cells again and saw that they had completely reverted to a stem-like state with markers of early glioma cells that could divide.”

This suggested to Professor Parrinello and team that mutations in certain genes synergised with brain inflammation, which is induced by acute injury and then increases over time during the natural process of ageing to make astrocytes more likely to initiate a cancer. Indeed, this process of change to stem-cell like behaviour accelerated when they injected mice with a solution known to cause inflammation.

The team then looked for evidence to support their hypothesis in human populations. Working with Dr Alvina Lai in UCL’s Institute of Health Informatics, they consulted electronic medical records of over 20 000 people who had been diagnosed with head injuries, comparing the rate of brain cancer with a control group, matched for age, sex and socioeconomic status. They found that patients who experienced a head injury were nearly four times more likely to develop a brain cancer later in life, than those who had no head injury. It is important to keep in mind that the risk of developing a brain cancer is overall low, estimated at less than 1% over a lifetime, so even after an injury the risk remains modest.

Professor Parrinello said: “We know that normal tissues carry many mutations which seem to just sit there and not have any major effects. Our findings suggest that if on top of those mutations, an injury occurs, it creates a synergistic effect. In a young brain, basal inflammation is low so the mutations seem to be kept in check even after a serious brain injury. However, upon ageing, our mouse work suggests that inflammation increases throughout the brain but more intensely at the site of the earlier injury. This may reach a certain threshold after which the mutation now begins to manifest itself.”

Source: University College London