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New technique brings lasting pain relief for rotator cuff disease

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People living with spinal cord injury can experience lasting pain relief through the injection of micro-fragmented adipose tissue (MFAT) for rotator cuff disease, new research has revealed. 

A team of specialists in regenerative rehabilitation have shown through a pilot study that MFAT can deliver benefits to wheelchair users who experience shoulder problems. 

In the study, nearly 80 per cent of participants saw a meaningful decrease in pain symptoms through an ultrasound-guided injection of MFAT, and all but one reported some improvement in pain and function. 

Scores also declined steadily over the first three months for all metrics, and over the entire year for the BPI-17 pain metric, suggesting that this intervention has long-lasting effects.

“These results show that the minimally invasive injection of micro-fragmented adipose tissue is a safe and efficacious option for wheelchair users with shoulder pain caused by rotator cuff disease,” says Dr Gerard Malanga, author of the study and visiting scientist at Kessler Foundation. 

Shoulder pain is a common occurrence among wheelchair users with spinal cord injury because they rely solely on their upper limbs to perform everyday tasks. 

Often, pain is caused by soft-tissue injuries such as damage to rotator cuff tendons. Many non-surgical therapies for shoulder pain exist, including pain medication, physical therapy, and equipment modifications, but these have shown limited efficacy. 

Persistent shoulder pain can significantly lessen quality of life, and if conservative therapies fail, shoulder surgery is frequently the only option, which comes with its own set of risks and potential setbacks.

Through the single-group pilot study, researchers explored the efficacy of a minimally invasive biological intervention involving MFAT, which has a potential source of bioactive and regenerative components for orthopaedic conditions and may provide cushioning that can improve function and alleviate pain caused by rotator cuff injuries.

Ten wheelchair users with chronic spinal cord injury who had moderate to severe shoulder pain for more than six months caused by refractory rotator cuff disease participated in the study. 

All received an injection of MFAT and were evaluated at six and 12 months after treatment. 

Evaluation metrics included the 11-point Numerical Rating Scale, the Wheelchair User’s Shoulder Pain Index, Brief Pain Inventory pain interference items (BPI-17), Patient Global Impression of Change, ultrasound and physical examinations, and adverse events.

“Based on the success of our study, a randomised controlled study with a larger number of subjects has been initiated in this patient population through funding from the New Jersey Commission for Spinal Cord Research,” says Dr Malanga. 

“We feel there is great potential for this therapy to help people with shoulder pain manage their symptoms and improve their quality of life.”

Brain injury

TBI leads to neurodegenerative diseases through protein build-up – research

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Scientists have revealed a potential mechanism for how traumatic brain injury leads to neurodegenerative diseases.

The results could aid the development of treatments that halt the progression of cell damage after brain injury, which can otherwise lead to neurological diseases such as amyotrophic lateral sclerosis (ALS), and Alzheimer’s and Parkinson’s disease.

Repeated head trauma is linked to a progressive neurodegenerative syndrome, chronic traumatic encephalopathy (CTE). 

Postmortem tissues from patients with CTE show dysfunctional levels of a molecule called TDP-43, which is also found in ALS, Alzheimer’s disease and frontotemporal dementia.

“Although TDP-43 is a known indicator of neurodegeneration, it was not clear how repeated trauma promotes the build-up of TDP-43 in the brain,” explains first author Eric Anderson, postdoctoral research associate at the Department of Pediatrics at the University of Pittsburgh. 

“We have shown that repetitive brain trauma in fruit flies leads to a build-up of TDP-43. In this study we measured the changes of proteins in the fruit fly brain post injury to identify the molecular pathways that cause this.”

In the study of fruit flies, and rat and human brain tissue, from an analysis of 2,000 proteins, the team identified 361 that significantly changed in response to injury. 

These included components of the nuclear pore complex (NPC) involved in nucleocytoplasmic transport – the shuttling of important cargoes between the cell nucleus and the rest of the cell.

They found that a family of molecules that make up the NPC called nucleoporins (Nups) were increased in both larval and adult flies after injury. 

When they looked at the distribution pattern of Nups around the edge of the nucleus in fruit fly nerve cord cells, they found it was altered after brain trauma: there were gaps in the nuclear membrane and clumps of Nups. 

They also found changes in a key enzyme involved in transporting molecules in and out of the nucleus in injured brains. As a result, the transport of fluorescently labelled cargo in and out of the nucleus was impaired.

Having established that brain injury impairs the transport machinery between the nucleus and the rest of the cell, the team looked at whether the build-up of Nups leads to the aggregation of TDP-43 seen in neurodegenerative diseases. 

They created fruit flies that produce excess Nup protein and then stained the brain cells for the fruit fly version of TDP-43, called Tbph. They found a significant increase in the number of Tbph deposits in brains that had too much Nup compared with normal brains. 

Moreover, these high levels of Nups were also toxic to the flies, causing decreased motor function and reducing the distance they could climb in a certain timeframe. When the level of Nups was reduced in cells after injury, this improved the flies’ climbing ability and lifespan, highlighting an avenue to explore for new treatments.

Finally, the team looked at whether the increased build-up of a Nup molecule (Nup62) was also seen in human brain tissue after injury. They examined postmortem brain tissue from patients with mild and severe CTE matched to healthy tissue from people of the same age. 

All mild and severe patients were involved in sports, while healthier cases were not. 

They found that Nup62 was present in large amounts in the wrong place in patients with mild and severe disease, but not in the healthy group, and the degree of Nup62 aggregation increased with the severity of disease. 

They also saw similar changes in the distribution of Nup62 in a rat model of traumatic brain injury.

“Our study reveals that traumatic brain injury can disrupt nuclear transport machinery of the cells, which plays an essential role in normal cell functions such as communication,” concludes senior author Udai Pandey, associate professor of pediatrics, human genetics and neurology at the University of Pittsburgh School of Medicine. 

“This suggests that the accumulation of neurodegenerative hallmark proteins caused by injury begins with these nuclear transport defects, and that targeting these defects could be a strategy for preventing trauma-induced neurological disorders.”

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Risk calculator ‘will save many lives from stroke or heart attack’

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A new risk calculator will better predict people at high risk of stroke or heart attack years before they strike and is ready for use across the UK and Europe, it has been announced. 

The risk calculator, SCORE2, will be adopted by the upcoming European Guidelines on Cardiovascular Disease Prevention in Clinical Practice, and enables doctors across Europe in the next ten years with greater accuracy than ever before.

The research team behind the breakthrough say this new prediction tool will help save many more people across Europe from having a potentially deadly heart attack or stroke, ultimately saving lives. 

People who are flagged as having an increased risk can be put on personalised preventative treatment, such a statins, or will receive lifestyle advice to lower their risk.

“This risk tool is much more powerful and superior than what doctors have used for decades. It will fit seamlessly into current prevention programmes with substantial real-world impact by improving the prevention of cardiovascular diseases across Europe before they strike,” says Professor Emanuele Di Angelantonio at the University of Cambridge British Heart Foundation (BHF) Centre of Research Excellence.

Around 200 investigators from across Europe were involved in the development of SCORE2, with data analysed from nearly 700,000 participants – mostly middle-aged – from 45 different studies. The tool has also been tailored for use in different European countries.

Participants had no prior history of heart and circulatory disease when they were recruited to the studies, and in the ten years they were followed up, 30,000 had a ‘cardiovascular event’ – including fatal or non-fatal heart attack or stroke.

The risk tool was then statistically ‘recalibrated’, by using regional-specific cardiovascular and risk factor data from 10.8 million people, to more accurately estimate cardiovascular risk for populations split into four European risk regions. 

The tool uses known risk factors for heart and circulatory diseases such as age, sex, cholesterol levels, blood pressure and smoking.

This is a much-needed upgrade from the previous prediction tool that was developed using data before 1986 and underestimated the cardiovascular risk in some countries. The new SCORE2 risk calculator now accounts for current trends in heart and circulatory diseases, can predict both fatal and non-fatal conditions and is adaptable to countries with different levels of risk.

The researchers say that this upgrade will better estimate the cardiovascular risk amongst younger people, and will improve how treatment is tailored for older people and those in high-risk regions across Europe.

Dr Lisa Pennells, from Cambridge’s BHF Centre of Research Excellence, says: “This project was a highly collaborative effort that has brought together key experts and extensive data sources to develop improved risk prediction tools for cardiovascular disease for use across the UK and Europe.

“A key feature is that our calculators are relevant to current day rates of cardiovascular disease in different regions of Europe. Importantly, our methods allow them to be easily updated using routinely collected data in the future to ensure they stay relevant as trends in heart and circulatory diseases change.”

This study was carried out by the SCORE2 Working Group and the European Society of Cardiology Cardiovascular Risk Collaboration. It was supported by organisations including the British Heart Foundation, the Medical Research Council, National Institute for Health Research Cambridge Biomedical Research Centre and Health Data Research UK.

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Brain injury

Impact of domestic violence on the brain to be investigated

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The lifelong consequences of domestic violence on brain health are to be investigated through new research. 

The Drake IPV Study – led by the University of Glasgow in collaboration with the University of Edinburgh, and funded by The Drake Foundation – will examine individuals exposed to domestic abuse, many of whom currently report a history of traumatic brain injury.

The research – overseen by Professor Willie Stewart, who leads multiple collaborative research programmes exploring outcomes from traumatic brain injury – recognises the growing awareness of the association between brain injury and increased risk of neurodegenerative disease, including dementia.

Domestic abuse – or intimate partner violence – is all too common, with global estimates suggesting approximately 30 per cent of women over age 15 years will have been exposed to physical or sexual intimate partner violence. 

However, there remains a lack of research in this issue, in particular the long-term consequences for those affected.

Recognising this, The Drake Foundation has awarded funding to this new study, in which researchers will look for any neuroimaging changes in the brains of individuals with a history of domestic abuse, as well as any changes that correlate with measures of exposure to traumatic brain injury, and compare these to population controls with no reported history of abuse.

“There is a need for robust investigations to better understand brain health outcomes following domestic abuse,” says Prof Stewart, consultant neuropathologist and Honorary Professor at the University of Glasgow.

“Traumatic brain injury is one important risk factor contributing to risk of dementia, but there has been remarkably little research looking at the potential lifelong outcomes of trauma from intimate partner violence.”

The Drake IPV Study will access unrivalled datasets from the internationally-regarded PREVENT Dementia Programme, led by Professor Craig Ritchie from the University of Edinburgh.

Prof Ritchie, chair of the Psychiatry of Ageing and director of the Centre for Dementia Prevention at the University of Edinburgh, says: “The PREVENT Dementia Programme always sought to understand the contribution of all risk factors for later life dementia and while it is now well known that head injury affects the risk of dementia, we also need to understand the source of that head injury to be able to work effectively to prevent and manage this effectively.

“This funding is so critical in bringing intimate partner violence out of the shadows in terms of dementia risk.”

Lauren Pulling, Drake Foundation’s CEO, adds: “The Drake Foundation is proud to be funding this new study into this largely under-researched area.

“With 30 per cent of women globally estimated to be exposed to IPV at some point in their lives, this is a critical area of research. 

“We hope that the Drake IPV Study will not only advance our knowledge of brain health in both IPV survivors and the general population, but also help to reduce the stigma around domestic abuse by bringing it into the open.”

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