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Cancer Risk Declines in Old Age – New Research Helps Explain Why

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Photo by Matteo Vistocco on Unsplash

When it comes to cancer, aging is a double-edged sword, researchers are increasingly learning. Age is considered the most important risk factor for cancer, due to the buildup of genetic mutations over time.

Now a study from researchers at Memorial Sloan Kettering Cancer Center (MSK) and their collaborators provides new evidence about how advanced age can also be protective against cancer. The study, conducted in a mouse model of lung cancer, was published in Nature.

“We know that as people get older, they’re more likely to get cancer,” says study first author Xueqian Zhuang, PhD, postdoc in the lab of senior study author Tuomas Tammela, PhD. “But there’s still a lot that’s unknown about how aging actually changes the biology of cancer.”

As with many types of cancer, lung cancer is diagnosed in most people around age 70, Dr Zhuang says. But once you get to 80 or 85, the incidence rate starts to come down again.

“Our research helps show why,” she adds. “Aging cells lose their capacity for renewal and therefore for the runaway growth that happens in cancer.”

Overall, the findings have two key implications, the researchers say:

  • First, they point to the underappreciated role that iron plays in aging cells’ ability to regenerate — suggesting that therapies that target iron metabolism may work better in younger people than older ones.
  • Second, they underline the potential value of early intervention and prevention efforts, targeting the window when most cancers initiate.

Cells’ regeneration ability linked to iron metabolism

To investigate why cancer incidence peaks in the early senior years and then starts to decline again, the MSK research team studied a genetically modified mouse model of lung adenocarcinoma, a common type of lung cancer that accounts for about 7% of all cancer deaths worldwide.

One of the things that makes it challenging to study aging in laboratory models is that mice take two years to develop to an age that’s equivalent to 65–70 years in people. The scientists found that as the mice get older, they make more of a protein called NUPR1. More NUPR1 makes the cells in the lungs function as if they are iron deficient.

“The aging cells actually have more iron, but for reasons we don’t yet fully understand, they function like they don’t have enough,” Dr Zhuang says.

Since the cells in the older mice functioned as though they didn’t have enough iron, they lost some of their ability to regenerate. And because that regenerative capacity is directly linked to the rise of cancer, the older mice developed far fewer tumours than their younger counterparts.

Intriguingly, this effect could be reversed by giving the older mice additional iron or by reducing the amount of NUPR1 in their cells.

“We think this discovery may have some immediate potential to help people,” Dr. Tammela says. “Right now, millions of people, especially following the COVID-19 pandemic, live with insufficient lung function because their lungs didn’t fully heal from an infection, or for some other reason. Our experiments in mice showed that giving iron can help the lungs regenerate, and we have really good ways of delivering drugs directly to the lungs – like asthma inhalers.”

But this is also where the double-edged nature of the discovery comes into play. By restoring the ability of the cells in the lungs to regenerate, one is also increasing the tissue’s ability to develop cancer, the study showed.

“So this type of approach might not be appropriate for people who are at a high risk of developing cancer,” he adds.

Older and younger patients may respond differently to iron-metabolism targeting treatments

The team’s findings also have important implications for therapies based on a type of cell death called ferroptosis, which is triggered by iron. Ferroptosis was discovered in 2012, and there are a number of ferroptosis-inducing small molecule compounds, as well as drugs previously approved by the FDA, that are being investigated for their potential to kill cancer cells.

Older cells are far more resistant to ferroptosis than younger cells because they function as if they don’t have enough iron, the researchers found. This means treatments that target ferroptosis may not be as effective in older patients as they are in younger ones.

“One of the things that we showed exploring all of this iron biology is that ferroptosis is tumour suppressive, as everybody suspected – but much more profoundly in younger animals,” Dr Tammela says.

Dr Zhuang adds: “To us, this says that because the biology of cells changes with aging, the sensitivity to drugs also changes. So doctors might need to really be careful in clinical trials, for example, to look at the effects in both older and younger patients.”

And for Dr Tammela, the research ultimately has an even bigger takeaway.

“What our data suggests in terms of cancer prevention is that the events that occur when we’re young are probably much more dangerous than the events that occur later,” he says. “So, preventing young people from smoking, or from tanning, or from other obvious carcinogenic exposures are probably even more important than we thought.”

Source: Memorial Sloan Kettering Cancer Center

Categories : Cardiovascular Disease ExerciseTags : Leave a comment

Bursts of Activity could Cut Heart Risk in Women

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Photo by Teona Swift on Unsplash

An average of four minutes of incidental vigorous physical activity a day could almost halve the risk of major cardiovascular events, such as heart attacks, for middle-aged women who do not engage in structured exercise, according to new research from the University of Sydney, published in the British Journal of Sports Medicine.

“We found that a minimum of 1.5 minutes to an average of 4 minutes of daily vigorous physical activity, completed in short bursts lasting up to 1 minute, were associated with improved cardiovascular health outcomes in middle-aged women who do no structured exercise,” said lead author Professor Emmanuel Stamatakis, Director of the Mackenzie Wearable Hub at the Charles Perkins Centre and the Faculty of Medicine and Health.

High-intensity physical activity that forms part of a daily routine is known as “vigorous intermittent lifestyle physical activity” (VILPA). Physical activity is incidental such as walking to the shops, vs exercise, which is structured, eg going to the gym. Longer sessions of VILPA are linked to significantly lower cardiovascular disease risk.

The researchers say that, given fewer than 20% of middle-aged or older adults engage in regular structured exercise, engaging in VILPA could be a good alternative.

“Making short bursts of vigorous physical activity a lifestyle habit could be a promising option for women who are not keen on structured exercise or are unable to do it for any reason. As a starting point, it could be as simple as incorporating throughout the day a few minutes of activities like stair climbing, carrying shopping, uphill walking, playing tag with a child or pet, or either uphill or power walking,” said Professor Stamatakis.

The study drew on UK Biobank data from 22 368 participants (13 018 women) aged 40–79 who reported they did not engage in regular structured exercise and who wore physical activity trackers for almost 24 hours a day for 7 days.

Cardiovascular health was monitored through hospital and mortality records, tracking major adverse cardiovascular events (MACE), such as heart attack, stroke, and heart failure, until November 2022.

After adjusting for factors such as lifestyle, socioeconomic position, cardiovascular health, co-existing conditions, and ethnicity, the researchers found that the more VILPA women did, the lower their risk of a major cardiovascular event.

Women who averaged 3.4 minutes of VILPA daily were 45 percent less likely to experience a major cardiovascular event. They were also 51% less likely to have a heart attack and 67 percent less likely to develop heart failure than women who did no VILPA.

Even when amounts of daily VILPA were lower than 3.4 minutes they were still linked to lower cardiovascular event risk. A minimum of 1.2 to 1.6 minutes of VILPA per day was associated with a 30 percent lower risk of total major cardiovascular events, a 33 percent lower risk of heart attack, and a 40 percent lower risk of heart failure.

However, men reaped fewer benefits from tiny bursts of VILPA. Those who averaged 5.6 minutes daily were only 16% less likely to experience a major cardiovascular event compared with men who did none. A minimum of 2.3 minutes per day was associated with only an 11% risk reduction.

Professor Stamatakis said more testing was needed to understand how VILPA may improve cardiovascular health.

“To date, it hasn’t been clear whether short bursts of VILPA lower the risk of specific types of cardiovascular events, like heart attack or stroke. We aimed to identify minimum daily thresholds and feasible amounts for testing in community programs and future trials,” he said.

“Importantly, the beneficial associations we observed were in women who committed to short bursts of VILPA almost daily. This highlights the importance of habit formation, which is not always easy. VILPA should not be seen as a quick fix – there are no magic bullets for health. But our results show that even a little bit higher intensity activity can help and might be just the thing to help people develop a regular physical activity – or even exercise – habit,” he said.

For the purposes of this story, physical activity is incidental, eg carrying shopping or briefly power walking, and exercise is structured, eg going to the gym or playing sport.

Source: University of Sydney

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Altered Gait after ACL Surgery Adds to More Knee Problems

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Photo by Towfiqu barbhuiya

For people with an injured anterior cruciate ligament (ACL) in the knee, surgical ACL reconstruction (ACLR) is an effective treatment for restoring joint stability, however, many treated patients still develop additional long-term knee problems, such as knee osteoarthritis. New research published in the Journal of Orthopaedic Research reveals that individuals exhibit an altered gait after ACLR, which can contribute to these problems.

For the study, investigators compared gait biomechanics between the ACLR and uninjured limbs of 58 patients who underwent ACLR and 58 uninjured control individuals.

Although gait biomechanics became more symmetrical in patients with ACLR over the first 12 months post‐ACLR, the ACLR and uninvolved limbs demonstrated persistent aberrant gait biomechanics compared with the uninjured control individuals.

“A persistent aberrant gait pattern following ACLR, like that observed in our study, can induce joint loads that may contribute to further long-term knee joint problems,” said corresponding author Christin Büttner, MS, of the University of North Carolina at Chapel Hill. Implementing early rehabilitative measures to normalise gait following ACLR could help to maintain long-term knee joint health in both the injured and uninjured limb.”

Source: Wiley

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Analysis of Repeat Mammograms Improves Cancer Prediction

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A new study describes an innovative method of analysing mammograms that significantly improves the accuracy of predicting the risk of breast cancer development over the following five years. Using up to three years of previous mammograms, the new method identified individuals at high risk of developing breast cancer 2.3 times more accurately than the standard method, which is based on questionnaires assessing clinical risk factors alone, such as age, race and family history of breast cancer.

The study, from Washington University School of Medicine in St. Louis, appears in JCO Clinical Cancer Informatics.

“We are seeking ways to improve early detection, since that increases the chances of successful treatment,” said senior author Graham A. Colditz, MD, DrPH, associate director, prevention and control, of Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. “This improved prediction of risk also may help research surrounding prevention, so that we can find better ways for women who fall into the high-risk category to lower their five-year risk of developing breast cancer.”

This risk-prediction method builds on past research led by Colditz and lead author Shu (Joy) Jiang, PhD, a statistician, data scientist and associate professor at WashU Medicine. The researchers showed that prior mammograms hold a wealth of information on early signs of breast cancer development that can’t be perceived even by a well-trained human eye. This information includes subtle changes over time in breast density, which is a measure of the relative amounts of fibrous versus fatty tissue in the breasts.

For the new study, the team built an algorithm based on artificial intelligence that can discern subtle differences in mammograms and help identify those women at highest risk of developing a new breast tumour over a specific timeframe. In addition to breast density, their machine-learning tool considers changes in other patterns in the images, including in texture, calcification and asymmetry within the breasts.

“Our new method is able to detect subtle changes over time in repeated mammogram images that are not visible to the eye,” said Jiang, yet these changes hold rich information that can help identify high-risk individuals.

At the moment, risk-reduction options are limited and can include drugs such as tamoxifen that lower risk but may have unwanted side effects. Most of the time, women at high risk are offered more frequent screening or the option of adding another imaging method, such as an MRI, to try to identify cancer as early as possible.

“Today, we don’t have a way to know who is likely to develop breast cancer in the future based on their mammogram images,” said co-author Debbie L. Bennett, MD, an associate professor of radiology and chief of breast imaging for the Mallinckrodt Institute of Radiology at WashU Medicine. “What’s so exciting about this research is that it indicates that it is possible to glean this information from current and prior mammograms using this algorithm. The prediction is never going to be perfect, but this study suggests the new algorithm is much better than our current methods.”

AI improves prediction of breast cancer development

The researchers trained their machine-learning algorithm on the mammograms of more than 10 000 women who received breast cancer screenings through Siteman Cancer Center from 2008–2012. These individuals were followed through 2020, and in that time 478 were diagnosed with breast cancer.

The researchers then applied their method to predict breast cancer risk in a separate set of 18 000 women who received mammograms from 2013–2020. Subsequently, 332 women were diagnosed with breast cancer during the follow-up period, which ended in 2020.

According to the new prediction model, women in the high-risk group were 21 times more likely to be diagnosed with breast cancer over the following five years than were those in the lowest-risk group. In the high-risk group, 53 out of every 1000 women screened developed breast cancer over the next five years. In contrast, in the low-risk group, 2.6 women per 1000 screened developed breast cancer over the following five years. Under the old questionnaire-based methods, only 23 women per 1000 screened were correctly classified in the high-risk group, providing evidence that the old method, in this case, missed 30 breast cancer cases that the new method found.

The mammograms were conducted at academic medical centres and community clinics, demonstrating that the accuracy of the method holds up in diverse settings. Importantly, the algorithm was built with robust representation of Black women, who are usually underrepresented in development of breast cancer risk models. The accuracy for predicting risk held up across racial groups. Of the women screened through Siteman, most were white, and 27% were Black. Of those screened through Emory, 42% were Black.

Source: Washington University School of Medicine in St. Louis

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Pretoria Company Aims to Lead SA in Making Key TB Drug Ingredients

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Source: Unsplash CC0

By Catherine Tomlinson

Though several South African companies are producing HIV and TB medicines, the active ingredients that go into these medicines are usually imported from India or China. Now, a local company is planning to break new ground by making the active ingredients for two important TB medicines in Pretoria. We zoom in on the company’s efforts and outline some of the obstacles to getting such local production off the ground.

South Africa has a relatively robust pharmaceutical sector. Approximately 60% of the medicines sold in South Africa are locally produced, according to Dr Senelisiwe Ntsele, writing in an opinion piece for the Department of Trade, Industry and Competition (dtic).

But most of the time we are not producing these medicines from scratch. In fact, like most countries in the world, we mostly import the ingredients that make the medicines work – commonly referred to as active pharmaceutical ingredients, or APIs. In addition to APIs, medicines contain other inactive substances that maintain their form and structure and assist in their delivery: such as binders, stabilisers, and disintegrants.

Around 98% of the APIs used in locally formulated medicines are imported and South Africa spends around R15 billion a year importing APIs, according to Ntsele.

Government has tried to address South Africa’s dependence on imported APIs as part of its broader strategy to bolster the local pharmaceutical industry, which is identified as a priority sector for investment in the country’s Industrial Policy Action Plan. Several government departments provide support to the local pharmaceutical sector, including for local establishment of API manufacturing capacity. These departments include the dtic, the Department of Science and Innovation (DSI), the Technology Innovation Agency (TIA), and the Industrial Development Corporation (IDC) – South Africa’s development finance instrument.

In a bid to reduce the country’s reliance on imported APIs, Ketlaphela – a state-owned API manufacturing company – was announced in 2012. The plan was that Ketlaphela would produce APIs used in HIV medicines, but after multiple setbacks the initiative never got off the ground. Spotlight reported on the history of Ketlaphela in more detail here.

Turning to the private sector

Less well known than Ketlaphela, are government’s efforts to support API manufacturing capacity in the private sector. One private company that has received such government support and seem set to start delivering is Pretoria-based Chemical Process Technologies Pharma (CPT Pharma) that was established in 2014.

CPT Pharma is a subsidiary of Chemical Process Technologies, a company with many years of experience in chemical manufacturing and synthesis, including manufacturing of APIs for animal medicines. Human medicines, CPT Pharma’s core business, have stricter production management and quality control standards than those for animal medicines.

Dr Hannes Malan, Managing Director of CPT Pharma, told Spotlight that the company has 14 APIs in its pipeline, with a strong focus on TB medicines.

CCPT Pharma is a subsidiary of Chemical Process Technologies. (Photo: Supplied)

In 2023, the company secured a license from USAID to produce API for rifapentine, a drug widely used for TB prevention, and in 2022 they secured a licence from the Medicines Patent Pool to produce API for molnupiravir, a treatment for COVID-19. Malan pointed out that these two licenses were agreed with organisations aiming to expand the presence of API manufacturers in Africa – unlike typical arrangements driven by pharmaceutical companies looking to secure their own supply chains.

“For all the other APIs that we’re working on [beyond molnupiravir and rifapentine], we’re either working on technical packs [technical information about the API] that were available in the public domain or technologies that we’ve developed ourselves,” said Malan.

“Our approach has always been to look at the molecules, look at the market value, look at the technology, and then see if there’s an opportunity for us to develop technology that allows us to produce these compounds cost competitively,” he said.

“We really believe that to be competitive and independent, you have to have your own technology. Doing a technology transfer from Big Pharma does not make you independent,” Malan added.

How to fund it all?

In 2017, the company completed a pilot plant for making APIs. Then in 2020 it received approval from the South African Health Products Regulatory Authority (SAHPRA) to produce APIs for human use. The plant was built for R50 million, funded jointly by the IDC, TIA, and CPT Pharma.

Malan said that that the IDC and TIA also supported trial runs to test CPT Pharma’s manufacturing processes and technology. These tests included several APIs in development, such as isoniazid, a drug commonly used to prevent and treat TB.

The company has also secured funding from several international donors. The Gates Foundation provided support to develop manufacturing technology for the anti-malarial drug amodiaquine, as well as tuberculosis medicines bedaquiline and pretomanid. GIZ, a German development agency involved in a European Union project to boost vaccine and health product production in Africa, supported the company’s work on molnupiravir and dolutegravir – a widely used HIV medicine. USAID and the DSI are supporting the company’s work on developing rifapentine API manufacturing capacity.

Most of this financial support has been in the form of grants.

Still building new plants

While CPT Pharma has secured local and international funding to help construct a pilot plant and to develop its API manufacturing technology and processes, Malan said more investment is needed to support the construction of two commercial-scale manufacturing facilities: an isoniazid API manufacturing plant and a multiple API manufacturing facility.

Construction of the isoniazid manufacturing plant has already commenced using existing land and infrastructure with support from the IDC, but it is short of around R20 million to complete it, said Malan.

Although the plant is not yet operational, he said a company has already expressed interest in buying CPT Pharma’s locally produced isoniazid API. This company, said Malan, is contracted to supply isoniazid to government. The plan is to initially supply the company with isoniazid API produced at its pilot plant

Malan said the commercial plant, when built, will be able to manufacture enough isoniazid API to supply around 60% of local demand.

Things are less far down the road with plans for a plant to produce multiple different APIs at commercial scale, and more work is needed to understand the financing requirements for this type of facility, said Malan. “We want to do a bankable study and a concept design for such a plant,” he said. Based on CPT Pharma’s own experience, published data, and the required complexity and capacity of the plant, Malan said it is estimated that construction for the multi-API plant will cost around US$100 million or R1.8 billion.

Plans to commercialise

Meanwhile, the company is moving forward with plans to commercialise isoniazid and rifapentine API from its pilot plant. Isoniazid and rifapentine is increasingly used together as TB preventive therapy.

“For rifapentine, our pilot plant is seen as the commercial plant,” said Malan. “At this stage, we can use the pilot facility and the pilot reactor to produce enough rifapentine to get into the market and to grow the market.” But in the long term he said the company hopes to transfer rifapentine manufacturing to a larger commercial plant.

The company is also planning to apply for World Health Organization (WHO) pre-qualification status for its rifapetine API. The goal is to conduct demonstration runs in the pilot plant by June 2025 and validate the WHO pre-qualification application in September 2025.

If achieved, WHO pre-qualification of CPT Pharma’s rifapetine API would show that the company’s APIs meet high-quality standards. It would also allow CPT Pharma to supply rifapentine API to companies producing medicines for the broader African market, for which a significant proportion of medicines are procured by donors requiring WHO PQ approval.

Note: The Gates Foundation is mentioned in this article. Spotlight receives funding from the Gates Foundation. Spotlight is editorially independent – an independence that the editors guard jealously.  Spotlight is a member of the South African Press Council.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

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PVA Glue Boosts Effects of an Advanced Radiotherapy Treatment

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Photo by National Cancer Institute on Unsplash

Treatment for more advanced and difficult-to-treat head and neck cancers can be improved with the addition of polyvinyl alcohol (PVA), the same ingredient used in children’s glue. Researchers found that combining PVA with a boron-containing compound, D-BPA, improved the effects of a type of radiation therapy for cancer, compared to currently clinically used drugs. The PVA made the drug more selective of tumour cells and prolonged drug retention, helping to spare healthy cells from unnecessary radiation damage.

Japan became the first country to approve boron neutron capture therapy (BNCT), a type of targeted radiotherapy for cancer, in 2020. Doctors administer a boron-containing drug to patients, which is designed to selectively accumulate in tumour cells. The patients are then exposed to low-energy neutrons, which react with the boron, destroying cancer cells without damaging healthy cells.

The advantages of BNCT are that it targets only boron-containing cells, meaning that damage to healthy cells is less compared to some other treatments. It has also been found to be effective against some more challenging and recurring cancers. However, because low-energy neutrons are quite weak, their use is limited to certain areas of the body. Currently, they are approved for head and neck cancers, which are nearer the surface. Their effectiveness also depends on both the level and retention of boron within tumour cells for the duration of the treatment.

In newly published research, special research student Kakeru Konarita and Associate Professor Takahiro Nomoto from the University of Tokyo found that adding PVA to the boron-containing compound greatly improved both its accumulation and retention in cancer cells.

“We discovered that PVA, which is used in liquid glue, dramatically improves the efficacy of a compound called D-BPA, that until now has been removed from drug ingredients because it was considered useless,” explained Nomoto.

Neither PVA nor D-BPA exhibit pharmacological activity when administered alone. However, combining these compounds resulted in remarkably elevated tumour accumulation, prolonged retention and potent therapeutic efficacy, even when compared with a clinically used drug.”

Currently, the chemical substance L-BPA is the only approved boron compound for BNCT. It accumulates well within cancer cells, but, depending on the location of the cancer, can also enter some healthy cells. This makes it unsuitable for treating certain tumours. D-BPA is the enantiomer of L-BPA, meaning that its molecular structure is the mirror image of L-BPA but it is otherwise chemically identical. D-BPA appealed to the researchers because it appears to be more selective of cancer cells. However, on its own it doesn’t accumulate, which is why it was considered useless.

The team previously found that mixing PVA with L-BPA improved its effectiveness. In this latest research, they combined PVA with D-BPA and were surprised to see even higher levels of boron accumulating and more prolonged retention.

“There are many demands in the development of drugs for cancer treatment and much recent research and development has focused on complex combinations of expensive molecules,” said Nomoto. “However, we are concerned that such methods, when put into practice, will be so expensive that only a limited number of patients will benefit. In this study, we aimed to develop a drug with a simple structure and high functionality at a low cost.”

Now the team is promoting joint industry-academia collaboration to further this research and hope to apply this achievement to the treatment of other challenging cancers.

Source: University of Tokyo

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T Cells could Ease Brain Injury after Cardiac Arrest

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Photo by Mat Napo on Unsplash

Despite improvements in CPR and ambulance response times, only about one in 10 people ultimately survive after out-of-hospital cardiac arrest (OHCA). Most patients hospitalised with OCHA die of brain injury, and no medications are currently available to prevent this outcome. A team led by researchers from Mass General Brigham found that immune cells may play a key role.

Using samples from patients who have had an OHCA, the team uncovered changes in immune cells just six hours after cardiac arrest that can predict brain recovery 30 days later. They pinpointed a particular population of cells that may provide protection against brain injury and a drug that can activate these cells, which they tested in preclinical models. Their results are published in Science Translational Medicine.

“Cardiac arrest outcomes are grim, but I am optimistic about jumping into this field of study because, theoretically, we can treat a patient at the moment injury happens,” said co-senior and corresponding author Edy Kim, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital. “Immunology is a super powerful way of providing treatment. Our understanding of immunology has revolutionised cancer treatment, and now we have the opportunity to apply the power of immunology to cardiac arrest.”

As a resident physician in the Brigham’s cardiac intensive care unit, Kim noticed that some cardiac arrest patients would have high levels of inflammation on their first night in the hospital and then rapidly improve. Other patients would continue to decline and eventually die. In order to understand why some patients survive and others do not, Kim and colleagues began to build a biobank – a repository of cryopreserved cells donated by patients with consent from their families just hours after their cardiac arrest.

The researchers used a technique known as single-cell transcriptomics to look at the activity of genes in every cell in these samples. They found that one cell population – known as diverse natural killer T (dNKT) cells – increased in patients who would have a favourable outcome and neurological recovery. The cells appeared to be playing a protective role in preventing brain injury.

To further test this, Kim and colleagues used a mouse model, treating mice after cardiac arrest with sulfatide lipid antigen, a drug that activates the protective NKT cells. They observed that the mice had improved neurological outcomes.

The researchers note that there are many limitations to mouse models, but making observations from human samples first could increase the likelihood of successfully translating their findings into intervention that can help patients. Further studies in preclinical models are needed, but their long-term goal is to continue to clinical trials in people to see if the same drug can offer protection against brain injury if given shortly after cardiac arrest.

“This represents a completely new approach, activating T cells to improve neurological outcomes after cardiac arrest,” said Kim. “And a fresh approach could lead to life-changing outcomes for patients.”

Source: Mass General Brigham

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An Internationally Standardised Set of Handgrip Strength Norms

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Convenient, safe, and non-invasive, ‘handgrip strength’ is a reliable predictor for age-related disease and disability. Now, a groundbreaking study has created the world’s largest and most geographically comprehensive international norms for handgrip strength, enabling global peer-comparison, health screening and surveillance across the adult lifespan.

Published in The Journal of Sport and Health Science, the new norms are based on 100 unique observational studies representing 2.4 million adults aged 20 to 100+ years, from 69 countries (representing six of the seven continents, 17 of 22 United Nations’ geographical subregions, and 71% of the world’s population). The study was led by the University of South Australia and conducted in collaboration with 140 authors across the globe.

It is the first time that norms have been reported for handgrip strength across different age groups and sexes at the international level.

Handgrip strength, or isometric grip, is measured via a handgrip dynamometer which is gripped and squeezed to record the maximum force a person can produce over a few seconds. A person with low handgrip, or low muscle strength, has a higher risk of death from all causes and cardiovascular disease as well as a higher incidence of physical disability.

The new study has established a percentile framework that ranks strength. Adults below the 20th percentile are considered to have ‘low’ strength; those between 20-39th percentiles have ‘somewhat low’ strength; those in the 40-59th percentiles have ‘moderate’ strength; those in the 60-79th percentiles have ‘somewhat high’ strength; and those at or above the 80th percentile having ‘high’ strength.

Importantly, norms can be used to monitor healthy aging by examining changes in strength over time.

Finally, international benchmarks for comparison

Lead researcher Professor Grant Tomkinson says the new norms will help clinicians better identify people who may be at risk of poor health and in need of interventions.

“Muscle strength, which reflects the ability of the muscles to produce force maximally, is a powerful biomarker of current and future health,” Prof Tomkinson says. “A good general measure of overall muscle strength is how hard you can grip. Grip strength improves a little throughout early adulthood, peaks between age 30 and 39, and then drops off as people age, especially in late adulthood.

“By establishing international handgrip norms through a reference population, we can determine how well someone compares to their peers of the same age and sex, and quickly identify people who need intervention.

“But until now, there has been no international markers by which to compare or benchmark.

“Our research has established robust international norms that enable clinicians and exercise professionals to interpret and relate results in a percentile ranking. For example, adults below the 20th percentile are considered to have ‘low’ strength, those between 20-39th percentiles have ‘somewhat low’ strength, and so on as the scale progresses.

“So, what we have developed is an international guideline and benchmark that enables clinicians to compare and track muscle strength – and therefore potential health risks – across the adult lifespan.”

The new norms will enable standardised grip strength test results for cross- and within-country comparisons, to identify trends over time, monitor improvements and evaluate the effectiveness of implemented public health policies. They will also facilitate individual feedback, advice, and health interventions for those at risk.

Source: University of South Australia

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Gluten Free Diet Reduces Coeliac Symptoms – and ‘Good’ Gut Bacteria

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Photo by Mariana Kurnyk: https://www.pexels.com/photo/two-baked-breads-1756062/

A research team led by the University of Nottingham has used magnetic resonance imaging (MRI) to better understand the impact a gluten free diet has on people with coeliac disease, which could be the first step towards finding new ways of treating the condition.

The MARCO study – MAgnetic Resonance Imaging in COliac disease is published in Clinical Gastroenterology and Hepatology (CGH) (link connects to BioRxiv copy).

Coeliac disease is a chronic condition affecting around one person in every 100 in the general population. When people with coeliac disease eat gluten, which is found in pasta and bread, their immune system produces an abnormal reaction that inflames and damages the gut tissue and causes symptoms such as abdominal pain and bloating.

The only treatment is a life- long commitment to a gluten free diet, which helps recovery of the gut tissue but still leaves many patients with gastrointestinal symptoms.

Luca Marciani, Professor of Gastrointestinal Imaging at the University, led the study. He said: “Despite being a common chronic condition, we still don’t precisely know how coeliac disease affects the basic physiological functioning of the gut and how the gluten free diet treatment may further change this.

“We launched the MARCO study to try and address this issue, by using MRI along with gut microbiome analysis to give us new insights into how a gluten-free diet affects people with coeliac disease.”

The team recruited 36 people who had just been diagnosed with coeliac disease and 36 healthy volunteers to participate in the study. Images were taken of their guts with MRI, along with blood and stool samples. The patients then followed a gluten free diet for one year and came back to repeat the study. The healthy participants came back one year later too and repeated the study, but they did not follow any diet treatment.

The study found that the newly diagnosed patients with coeliac disease had more gut symptoms, more fluid in the small bowel and that the transit of food in the bowel was slower than in the healthy controls.

The microbiota (the ‘bugs’ living in the colon) of the patients showed higher levels of ‘bad bugs’ such as E.coli. After one year of a gluten free diet, gut symptoms, bowel water and gut transit improved in the patients, but without returning to normal values. But the gluten free diet also reduced some of the ‘good bugs’ in the microbiota, such as Bifidobacteria associated with reduced intake of starch and wheat nutrients, due to the different diet.

The patient study was conducted by Radiographer Dr Carolyn Costigan, from Nottingham University Hospitals, as part of her PhD studies at the University of Nottingham.

It was particularly interesting to see how the imaging results on gut function correlated with changes in the ‘bugs’ in the colon microbiota. The findings increase our understanding of gut function and physiology in coeliac disease and open the possibility of developing prebiotic treatments to reverse the negative impact of the gluten free diet on the microbiome.”

Luca Marciani, Professor of Gastrointestinal Imaging

Dr Frederick Warren from the Quadram Institute, which contributed to the research, said: “This study is the result of an exciting and innovative research collaboration bringing together medical imaging technology and gut microbiome analysis. We provide important insights which pave the way for future studies which may identify novel approaches to alleviate long-term symptoms in coeliac patients.”

Source: University of Nottingham

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Fire Breaks out at Netcare Pretoria East Hospital

On By ModernMedia
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A fire broke out yesterday, Thursday 5th December, at Netcare Pretoria East Hospital in Moreleta Park, prompting the evacuation of hundreds of patients. City of Tshwane firefighters promptly arrived on the scene, quickly getting the blaze under control. No injuries were reported.

Speaking to Newzroom Afrika, Netcare spokesperson Lynne O’Connor said that the fire was under control and with the Fire Marshal declaring that parts of the hospital to be safe, patients were being returned to their wards. As to the extent of damage and the cause, she said that “We know that the fire broke out somewhere near the theatre complex.”

As per the disaster management protocols, Netcare evacuated every single one of the approximately 200 patients in the hospital as soon as the alarm went off. The procedure was precautionary and none of the patients were harmed. O’Connor praised the swift response of the Tshwane emergency services. She said the cause of the fire was being investigated, and the extent of the damage would still need to be evaluated, News24 reports.

“We are grateful that everyone was brought to safety and sincerely apologise to the affected patients and their families for the inconvenience.”