Tag: 1/10/24

Hand-held Medical Scanner could Transform Cancer and Arthritis Diagnosis

PAT images of wrist vasculature acquired in high-resolution scan mode. Wrist region, (i) x-y and (ii) x-z depth-to-colour encoded MIPs, (iii) x-z and (iv) y-z greyscale MIP slices of regions indicated by dashed red and blue rectangles in (i) showing fine dermal microvasculature (DM), radial artery (RA) and large wrist veins. Inset: x-z greyscale MIP showing cross-sectional view of the radial artery and adjacent veins in the plane indicated by the dashed yellow line in (iv). Huynh et al., Nature Communications, 2024.

A new hand-held scanner developed by UCL researchers and tested in a series of clinical trials on UCLH patients can generate highly detailed 3D photoacoustic images in just seconds, paving the way for their use in a clinical setting for the first time and offering the potential for earlier disease diagnosis.

In the study, published in Nature Biomedical Engineering, the UCL and UCLH team show their technology can deliver photoacoustic tomography (PAT) imaging scans to doctors in real time, providing them with accurate and intricate images of blood vessels, helping inform patient care.

Photoacoustic tomography imaging uses laser-generated ultrasound waves to visualise subtle changes (an early marker of disease) in the sub-millimetre-scale veins and arteries up to 15mm deep in human tissues.

However, up until now, existing PAT technology has been too slow to produce high-enough quality 3D images for use by clinicians.

The older PAT scanners took more than five minutes to take an image – by reducing that time to a few seconds or less, image quality is much improved and far more suitable for people who are frail or poorly.

The researchers say the new scanner could help to diagnose cancer, cardiovascular disease and arthritis in three to five years’ time, subject to further testing.

In this study, the team tested the scanner during pre-clinical tests on 10 UCLH patients with type-2 diabetes, rheumatoid arthritis or breast cancer, along with seven healthy volunteers. They also compared the PAT scans to regular clinical scans taken at UCLH. Larger scale trials of the device are ongoing at UCLH and UCL.

In three patients with type-2 diabetes, the scanner was able to produce detailed 3D images of the microvasculature in the feet, highlighting deformities and structural changes in the vessels. The scanner was also used to visualise the skin inflammation linked to breast cancer.

UCLH consultant radiologist Andrew Plumb, a senior author of the study and Chief Investigator of the clinical PAT studies, said: “One of the complications often suffered by people with diabetes is low blood flow in the extremities, such as the feet and lower legs, due to damage to the tiny blood vessels in these areas. But until now we haven’t been able to see exactly what is happening to cause this damage or characterise how it develops.

“In one of our patients, we could see smooth, uniform vessels in the left foot and deformed, squiggly vessels in the same region of the right foot, indicative of problems that may lead to tissue damage in future. Photoacoustic imaging could give us much more detailed information to facilitate early diagnosis, as well as better understand disease progression more generally.” Dr Plumb is also Associate Professor of Medical Imaging at UCL.

Patients were identified and recruited from a number of clinics at UCLH, including consultant rheumatologist Madhura Castelino, consultant interventional radiologist Conrad von Stempel and research staff Katerina Soteriou and Antonia Yeung who co-ordinated safe, timely scanning at UCLH and UCL on the new PAT scanner.

UCL Professor of Biomedical Photoacoustics Paul Beard, corresponding author, said: “We’ve come a long way with photoacoustic imaging in recent years, but there were still barriers to using it in the clinic.

“The breakthrough in this study is the acceleration in the time it takes to acquire images, which is between 100 and 1000 times faster than previous scanners.

“This speed avoids motion-induced blurring, providing highly-detailed images of a quality that no other scanner can provide. It also means that rather than taking five minutes or longer, images can be acquired in real time, making it possible to visualise dynamic physiological events.

“These technical advances make the system suitable for clinical use for the first time, allowing us to look at aspects of human biology and disease that we haven’t been able to before.

“Now more research is needed with larger groups of patients to confirm our findings.”

Professor Beard added that a key potential use for the new scanner was to assess inflammatory arthritis, which requires scanning all 20 finger joints in both hands. With the new scanner, this can be done in a few minutes – older PAT scanners take nearly an hour, which is too long for elderly, frail patients, he said.

Source: University College London Hospitals

Artificial Spider Silk: A Next-generation Medical Material

Photo by Anthony Levlev on Unsplash

It’s almost time to dust off the Halloween decorations and adorn the house with all manner of spooky things, including the classic polyester spider webs. Scientists report in ACS Nano that they have made their own version of fake spider silk, but this one consists of proteins and heals wounds instead of haunting hallways. The artificial silk is strong enough to be woven into bandages that helped treat joint injuries and skin lesions in mice.

Spider silk is one of the strongest materials on Earth, technically stronger than steel for a material of its size. But it’s tough to obtain – spiders are too territorial (and cannibalistic!) to breed them like silkworms, leading scientists to turn to artificial options. Teaching microbes to produce the spider silk proteins through genetic engineering is one such option, but this has proved challenging because the proteins tend to stick together, reducing the silk’s yield. So, Bingbing Gao and colleagues wanted to modify the natural protein sequence to design an easily spinnable, yet still stable, spider silk using microbes.

The team first used these microbes to produce the silk proteins, adding extra peptides as well. The new peptides, following a pattern found in the protein sequence of amyloid polypeptides, helped the artificial silk proteins form an orderly structure when folded and prevented them from sticking together in solution, increasing their yield. Then, using an array of tiny, hollow needles attached to the nozzle of a 3D printer, the researchers drew the protein solution into thin strands in the air and spun them together into a thicker fibre. This setup acted like a giant artificial spider spinning its web.

They then wove their artificial silk fibres into prototype wound dressings that they applied on mice with osteoarthritis (a degenerative joint disease) and chronic wounds caused by diabetes. Drug treatments were easily added to the dressings, and the team found these modified dressings boosted wound healing better than traditional bandages. Compared with a control group with neutral dressings, mice with osteoarthritis showed decreased swelling and repaired tissue structure after 2 weeks of treatment, while diabetic mice with skin lesions treated with a similar dressing showed significant wound healing after 16 days of treatment. The new silken bandages are biocompatible and biodegradable, and the researchers say that they show promise for future applications in medicine.

Source: American Chemical Society

Over 100 Key Alzheimer’s Papers Found To Have Suspicious Data

Photo by National Cancer Institute on Unsplash

An investigation by Science has shown that over 100 key papers on Alzheimer’s research have used falsified data. The papers all have a common author – veteran neuropathologist Eliezer Masliah, a key researcher at the National Institute on Aging (NIA), typically as first or last author.

The investigation has found that scores of Masliah’s lab studies at the University of California San Diego (UCSD) and NIA are riddled with apparently falsified Western blots (images used to show the presence of proteins) and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, under supposedly different experimental conditions.

At UCSD, Masliah had amassed decades of experience researching Alzheimer’s and Parkinson’s disease, amassing 800 papers. Some important topics in them, such as alpha-synuclein (a protein linked to both diseases), continue to have great influence. The US Congress had released a flood of funding for Alzheimer’s research, US$2.6 billion for last year’s budget, far outstripping that for the rest of the NIA, and Masliah was an ideal choice for its neuroscience division director. This was a position which was enormously influential for Alzheimer’s research in the US as well as internationally, allowing him to fund selected research over and above others with better scores form peer-review.

One of the drugs being developed based on his work is prasinezumab, which failed to show benefit over placebo in a trial of 316 Parkinson’s patients – but resulting in a host of adverse effects, though none serious. The drug was based on an idea by Masliah and another scientist (whose papers were also seemingly doctored) that a vaccine-like approach could cause the body to create antibodies against harmful precursors in both Parkinson’s and Alzheimer’s.

Questions began to be raised about his research two years ago. These were assessed by a team of forensic analysts and a neuroscientist, who concluded, “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work.” They acknowledge that accidental duplication is a possibility, and that images can acquire artefacts resembling improper manipulation during the publication process.

Columbia University neurobiologist Mu Yang used specialised software to detect similarities and alterations in images. She had previously worked with the team investigating manipulation in Alzheimer’s and stroke data. In her analysis, duplicated sections in certain Western blots that had been “seamlessly blended” quickly floated into view, she said. “It tells me someone put a lot of thought and effort into the image … and usually indicates something is very wrong.”

A team of 11 neuroscientists was less charitable when they viewed the images. Samuel Gandy, a prominent neurologist at the Mount Sinai Alzheimer’s Disease Research Center said that he was “floored” by what he saw, noting that even a “bus driver” could see that two images of a mitochondrion published two years apart were identical. “Hundreds of images,” he said in a video interview. “There had to have been ongoing manipulation for years.”

In response to this latest dossier, the NIH issued a statement stating that there was a finding of “research misconduct” for Masliah over reuse of figures in two papers, further stating that Masliah no longer serves as NIA’s neuroscience division director. The NIH stated that it had started its own investigation in 2023.

Source: Science

Oestrogens are Implicated in More than Just Breast Cancers

Photo by National Cancer Institute on Unsplash

Oestrogens are known to drive tumour growth in breast cancer cells that carry its receptors, but a new study by Duke Cancer Institute researchers unexpectedly finds that oestrogens play a role in fuelling the growth of breast cancers without the receptors, as well as numerous other cancers.

Writing in the journal Science Advances, the researchers describe how oestrogens not only decrease the ability of the immune system to attack tumours, but also reduce the effectiveness of immunotherapies that are used to treat many cancers, notably triple-negative breast cancers. Triple-negative breast cancers are an aggressive form of disease that are negative for oestrogen, progesterone, and the HER2 receptor proteins.

Informed by retrospective analysis of patient data and experiments in mice, the researchers found that anti-oestrogen drugs reversed the effects of oestrogens, restoring potency to immunotherapies.

“The treatment for triple-negative breast cancer has been greatly improved with the advent of immunotherapy,” said senior author Donald McDonnell, PhD, professor at Duke University School of Medicine.

“Developing ways to increase the anti-cancer activity of immunotherapies is a primary goal of our research,” McDonnell said. “Here we have found a simple way bolster the effectiveness of immunotherapy for this type of breast cancer and the benefit was even seen in other cancers, including melanoma and colon cancers.”

McDonnell and colleagues, including lead author Sandeep Artham, a postdoctoral associate in the McDonnell lab, focused on a type of white blood cell called eosinophils, which are typically activated during allergic reactions and inflammatory diseases.

Eosinophils have recently been identified as important in tumours, and a phenomenon called tumour associated tissue eosinophilia, or TATE, is associated with better outcomes among patients with multiple types of cancer, including colon, oesophageal, gastric, oral, melanoma and liver cancers.

In their studies, the Duke team described how oestrogens decrease the number of eosinophils and TATE in mice. The hormone contributes to increased tumour growth in oestrogen receptor-negative breast cancer tumours and in melanoma tumours, which do not rely on oestrogen receptors for tumour growth.

Conversely, anti-oestrogen therapies inhibited oestrogen receptor signalling and enhanced the efficacy of immunotherapies, slowing tumour growth.

“These findings highlight the importance of oestrogen-receptor signalling as a regulator of eosinophil biology and TATE and highlight the potential near-term clinical application of anti-oestrogen drugs to increase the benefits of immunotherapies in multiple tumour types,” McDonnell said.

He said clinical trials are being planned using an investigational anti-oestrogen drug called lasofoxifene among patients with triple-negative breast cancers.

Source: Duke University Medical Center

Breast Cancer Knows no Gender: the Rising Need for Awareness, Early Detection, and Financial Preparedness

Breast cancer cells. Image by National Cancer Institute

Breast cancer is a significant health issue in South Africa, being the most common cancer among women, with a lifetime risk of 1 in 27. However, while breast cancer predominantly affects women, it is crucial to acknowledge that men can also develop the disease, and awareness needs to span genders. Early detection is key in improving outcomes, but the financial implications of treatment can be significant, as many medical aid schemes do not fully cover the extensive costs associated with treatment, including surgeries, chemotherapy, and follow-up care. Having gap cover in place can significantly ease the burden of out-of-pocket expenses, providing peace of mind for patients and their families.

Incidence on the rise

The latest statistics from the National Cancer Registry (NCR) indicate that breast cancer remains the most prevalent cancer among women in South Africa. According to the 2022 NCR report, breast cancer accounted for 20.4% of all cancers diagnosed in females, with a significant increase in incidence rates over the years. Although not very common, men also get breast cancer; approximately 1% of all breast cancer cases occur in men, and this number is also increasing.

Steve Kelly, a male breast cancer survivor, has been cancer-free for five years. “In December 2018, my partner spotted a lump in my right breast. It was painless, and I did not feel ill. It was diagnosed as stage 3 grade 3 breast cancer. I had surgery the following week, followed by six months of chemotherapy and six weeks of radiation therapy,” he explains.

While Kelly is one of the lucky ones, the reality is that many men who receive a diagnosis of breast cancer are not, because it is typically diagnosed late, which increases the mortality rate and also means that treatment has to be more aggressive. The increasing prevalence of breast cancer, along with the challenges of late-stage diagnoses, underscores the importance of early detection and education. Initiatives aimed at promoting regular screenings and self-examinations are vital for improving outcomes for all individuals affected by breast cancer in South Africa, including men.

Awareness is crucial

“Men do not scan and are generally poor at self-examination. More significantly, research shows that up to 33% of men would not seek medical attention if they found a painless lump in their breast. Because of embarrassment or ignorance, men would often present later with a more advanced breast cancer and a worse prognosis,” Kelly says.

Awareness campaigns need to evolve to become more inclusive. However, they also need to evolve to effectively target women, given the growing prevalence of breast cancer as well as the fact that it is increasingly affecting women at younger ages. Regular self-examination is a critical element in the early detection of breast cancers in both women and men, and having appropriate testing in place is essential.

Joanne Stroebel is another breast cancer survivor, and she credits her early diagnosis and successful treatment to her healthy lifestyle and her regular self-screenings. “Have your screenings done regularly and make sure to self-examine at least once a month. Once you have been diagnosed, involve your medical aid broker (or get one that knows the systems) and let them help you with the claims. The healthcare system can be very daunting when you have a new diagnosis, and extra stress is the last thing you need,” she recommends.

Easing the financial strain

Having medical aid is important in covering the cost of breast cancer treatment, but the reality is that many medical aid schemes do not fully fund treatments. There are many areas where you could potentially incur out-of-pocket expenses. Surgery is typically involved, which often comes with shortfalls on doctors’ accounts, such as surgeons and anaesthetists.

Prophylactic bilateral mastectomy (the preventative removal of both breasts) is generally not covered, and neither is reconstruction. Making use of a doctor who is not in a Designated Service Provider (DSP) network means additional shortfalls and co-payments. Medical aids also cover cancer in one of two ways: they either have an annual limit for cancer treatment, and once this is depleted you will only have access to Prescribed Minimum Benefits (PMBs); or they will cover you up to a certain Rand value, and once this is depleted you will incur a 20% co-payment on anything related to oncology treatment as well as the treatment itself.

Gap cover can go a long way toward alleviating the financial burden of breast cancer treatment. If your medical aid pays a lump sum, once this is depleted, then gap cover can assist with funding ongoing treatment, including in-hospital as well as outpatient treatment, pathology, and biological drugs, if these were covered by your medical aid. Gap cover can also help to pay the 20% co-payment, which can add up to significant sums, especially around biological drugs.

“Nearly a quarter (23.3%) of all Turnberry cancer claims are for breast cancer, and the highest individual claim we have seen is in excess of R80 000 resulting in a total treatment cost of more than R170 000. This is not an outlying number either – individual claims are frequently in the tens of thousands of Rands, and total treatment cost is usually over R100 000,” says Brian Harris, GM: Operations at Turnberry Management Risk Solutions.

Stroebel concludes, “Being a medical aid specialist, I was fortunate that I had the best cover available for cancer treatment. I never thought that I would need to try and raise funds for treatment, as I was confident that my medical aid and gap cover would cover any shortfalls, which was absolutely the case. I also had a dread disease policy that paid out, and being financially secure meant I never had unnecessary stress. Talk to your broker to make sure you have the best cover to suit your needs.”