Tag: 23/1/24

What Makes Men Opt for Active Surveillance in Low-risk Prostate Cancer

Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

Because low-risk prostate cancer is unlikely to spread or impact survival, experts and guidelines recommend active surveillance, which involves regular monitoring and thus avoid or delay treatment like surgery or radiation therapy and their life-changing complications. A new study examined the rates of active surveillance use and evaluated the factors associated with selecting this management strategy over surgery or radiation, with a focus on underserved Black patients who have been underrepresented in prior studies. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

For the study, called the Treatment Options in Prostate Cancer Study, Jinping Xu, MD, MS, of Wayne State University, and her colleagues analysed data from metro-Detroit, Michigan, and Georgia cancer registries, focusing on patient self-reported information related to Black and White patients who were newly diagnosed with low-risk prostate cancer in 2014–2017.

Among 1688 patients, 57% chose active surveillance (51% of Black patients and 61% of White patients) over other treatments. After adjusting for other influencing factors, the strongest determinant of active surveillance uptake was a urologist’s recommendation to choose this option. Other factors linked with the decision to undergo active surveillance included a shared patient-physician treatment decision and greater knowledge about prostate cancer. Also, participants living in metro-Detroit were more likely to choose active surveillance than those living in Georgia.

Conversely, men were less likely to try active surveillance if their considerations were strongly influenced by the desire to achieve a “cure” or they expected to “live longer” with treatment, or if they perceived that their low-risk prostate cancer diagnosis was more “serious.”

Education and interventions for patients and especially urologists that address these factors may increase the use of recommended active surveillance among individuals with low-risk prostate cancer.

“I am glad to see that the majority of our study participants selected active surveillance, which indicates that acceptance has improved over the last decade; however, there is room for greater acceptance. Our study findings shed new light on potentially modifiable factors that can help further increase active surveillance use among patients with newly diagnosed low-risk prostate cancer to avoid unnecessary invasive treatment and improve their quality of life,” said Dr Xu.

Source: Wiley

Low-frequency Ultrasound Improves Blood Oxygenation

Source: CC0

Research conducted by a team of scientists from Kaunas universities, Lithuania, revealed that low-frequency ultrasound influences blood parameters. The findings suggest that ultrasound’s effect on haemoglobin can improve oxygen’s transfer from the lungs to bodily tissues.

The research was undertaken on 300 blood samples collected from 42 pulmonary patients.

The samples were exposed to six different low-frequency ultrasound modes at the Institute of Mechatronics of Kaunas University of Technology (KTU). The calculations were made at the KTU Artificial Intelligence Centre.

Improved oxygen circulation and reduced blood pressure

KTU professors Vytautas Ostasevicius and Vytautas Jurenas say that the ongoing research papers are related to blood platelet aggregation.

The research of the KTU team revealed that the ultrasound affects not only platelet count but also red blood cells (RBC), which can result in better oxygen circulation and lowered blood pressure.

“During exposure to low-frequency ultrasound, aggregated RBCs are dissociated into single RBCs, whose haemoglobin molecules interact with oxygen over the entire surface area of RBCs, which is larger than that of aggregated RBCs and improves oxygen saturation in blood. The number of dissociated single RBCs per unit volume of blood decreases due to the spaces between them, compared to aggregates, which reduces blood viscosity and affects blood pressure,” explains Prof Ostasevicius, the Head of KTU Institute of Mechatronics.

The scientists claim that the effect of ultrasound on the haemoglobin in RBCs was higher than its impact on platelet aggregation, which is responsible for blood clotting.

Their findings have been supported by an additional analysis made at the LSMU Laboratory of Molecular Cardiology.

“This means that low-frequency ultrasound can be potentially used for improving oxygen saturation in lungs for pulmonary hypertension patients. Keeping in mind the recent COVID-19 pandemic, we see a huge potential in exploring the possibilities of our technology further,” says Prof Ostasevicius.

Partnership between medical and engineering scientists

In medicine, high-frequency ultrasound from 2 to 12MHz is used for both diagnostic and therapeutic purposes.

“Acoustic waves emitted by high-frequency ultrasound have a limited penetration depth into the body, so external tissues are more affected by high-frequency ultrasound than internal organs. Low-frequency ultrasound acoustic waves, penetrate deeper into the internal organs with a more uniform sound pressure distribution,” explains Prof Jurenas.

There are numerous applications for ultrasound in medical settings.

“For example, focused ultrasonic waves are used to break kidney stones, and to kill cancer cells. Maybe ultrasound can be used to activate certain medications. Or, to alleviate the delivery of antibiotics to the inflamed areas?” says Prof Jurenas.

The technology used in the above-described study is only one illustration of many successful working partnerships between engineers and physicians.

For example, just recently, the researchers of KTU Institute of Mechatronics have created the frame for immobilising the Gamma Knife radiosurgery patients at the Clinics of the Lithuanian University of Health Sciences.

“We believe, that using the know-how of different areas one can achieve greater results,” say KTU researchers about interinstitutional and interdisciplinary cooperation.

Source: Kaunas University of Technology

Could Bizarre Visual Symptoms Be a Telltale Sign of Alzheimer’s?

Photo by Mari Lezhava on Unsplash

A team of international researchers, led by UC San Francisco, has completed the first large-scale study of posterior cortical atrophy, a baffling constellation of visuospatial symptoms that present as the first signs of Alzheimer’s disease. These symptoms occur in up to 10% of cases of Alzheimer’s disease.

The study, which appears in The Lancet Neurology,  includes data from more than 1000 patients at 36 sites in 16 countries.

Posterior cortical atrophy (PCA) overwhelmingly predicts Alzheimer’s, the researchers found. Some 94% of the PCA patients had Alzheimer’s pathology and the remaining 6% had conditions like Lewy body disease and frontotemporal lobar degeneration. In contrast, other studies show that 70% of patients with memory loss have Alzheimer’s pathology.

Unlike memory issues, patients with PCA struggle with judging distances, distinguishing between moving and stationary objects and completing tasks like writing and retrieving a dropped item despite a normal eye exam, said co-first author Marianne Chapleau, PhD, of the UCSF Department of Neurology, the Memory and Aging Center and the Weill Institute for Neurosciences.

Most patients with PCA have normal cognition early on, but by the time of their first diagnostic visit, an average 3.8 years after symptom onset, mild or moderate dementia was apparent with deficits identified in memory, executive function, behaviour, and speech and language, according to the researchers’ findings.

At the time of diagnosis, 61% demonstrated “constructional dyspraxia,” an inability to copy or construct basic diagrams or figures; 49% had a “space perception deficit,” difficulties identifying the location of something they saw; and 48% had “simultanagnosia,” an inability to visually perceive more than one object at a time. Additionally, 47% faced new challenges with basic math calculations and 43% with reading.

We need better tools and training to identify patients

“We need more awareness of PCA so that it can be flagged by clinicians,” said Chapleau. “Most patients see their optometrist when they start experiencing visual symptoms and may be referred to an ophthalmologist who may also fail to recognise PCA,” she said. “We need better tools in clinical settings to identify these patients early on and get them treatment.”

The average age of symptom onset of PCA is 59, several years younger than the typical memory symptoms of Alzheimer’s. This is another reason why patients with PCA are less likely to be diagnosed, Chapleau added.

Early identification of PCA may have important implications for Alzheimer’s treatment, said co-first author Renaud La Joie, PhD, also of the UCSF Department of Neurology and the Memory and Aging Center. In the study, levels of amyloid and tau, identified in cerebrospinal fluid and imaging, as well as autopsy data, matched those found in typical Alzheimer’s cases. As a result, patients with PCA may be candidates for anti-amyloid therapies, like lecanemab (Leqembi), approved by the U.S Food and Drug Administration in January 2023, and anti-tau therapies, currently in clinical trials, both of which are believed to be more effective in the earliest phases of the disease, he said.

“Patients with PCA have more tau pathology in the posterior parts of the brain, involved in the processing of visuospatial information, compared to those with other presentations of Alzheimer’s. This might make them better suited to anti-tau therapies,” he said.

Patients have mostly been excluded from trials, since they are “usually aimed at patients with amnestic Alzheimer’s with low scores on memory tests,” La Joie added. “However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants.”

Better understanding of PCA is “crucial for advancing both patient care and for understanding the processes that drive Alzheimer’s disease,” said senior author Gil Rabinovici, MD, director of the UCSF Alzheimer’s Disease Research Center. “It’s critical that doctors learn to recognise the syndrome so patients can receive the correct diagnosis, counseling and care.

“From a scientific point of view, we really need to understand why Alzheimer’s is specifically targeting visual rather than memory areas of the brain. Our study found that 60% of patients with PCA were women – better understanding of why they appear to be more susceptible is one important area of future research.”

Source: University of California San Francisco

Few Patients Successfully Treat their Type 2 Diabetes Through Weight Loss

People with the most weight loss in the first year were most likely to achieve sustained remission

Photo by Andres Ayrton on Pexels

A new study finds that very few patients diagnosed with type 2 diabetes are able to achieve normal blood glucose levels through weight loss alone. A team led by Andrea Luk of the Chinese University of Hong Kong, report these findings January 23rd in the open access journal PLOS Medicine.

Clinical trials suggest that people with type 2 diabetes can control their blood glucose levels without medication if they lose weight and keep it off. However, it is unknown how many patients can achieve remission through weight loss alone under real-world conditions. In the new study, researchers looked at 37 326 people in Hong Kong who were newly diagnosed with type 2 diabetes to see whether – and low long – patients could control the disease through weight loss.

The researchers discovered that only 6% of people achieved diabetes remission solely through weight loss by about eight years after diagnosis. For people who initially achieved remission, two-thirds had elevated blood glucose levels by three years after diagnosis. These rates are significantly lower than in clinical trials, where remission occurred in up to 73% of patients at one year post-diagnosis. People with the greatest weight loss in the first year were most likely to have sustained remission.

The study shows that controlling type 2 diabetes through sustained weight loss is possible in real-world settings, but that few patients will achieve normal blood glucose levels through weight management alone, especially over the long-term. One reason for the discrepancy with clinical trials is that trial participants receive intensive lifestyle interventions, including holistic support for dietary changes, physical exercise and mental health. The researchers conclude that patients should receive early weight management interventions as a way to increase the odds that they will achieve sustained remission. Furthermore, the data suggest that early weight management interventions increase the odds of sustained remission and that sustained lifestyle changes are likely to be paramount.

Luk adds, “Greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission. However, the incidence of diabetes remission was low with only 6% of people achieving remission over 8 years, and half of those with initial remission returned to hyperglycaemia within 3 years indicating poor sustainability of diabetes remission in real-world setting.”

New Nanoparticle-based Oral Insulin could be Ready for Human Trials Next Year

Photo by Nataliya Vaitkevich on Pexels

Scientists have developed a ‘smart’ insulin which can be taken orally. The insulin is encapsulated within tiny nano-carriers, 1/10 000th the width of a human hair. The results of its testing in baboons were recently published in Nature Nanotechnology.

“This way of taking insulin is more precise because it delivers the insulin rapidly to the areas of the body that need it most. When you take insulin with a syringe, it is spread throughout the body where it can cause unwanted side effects,” explains Professor Peter McCourt at UiT Norway’s Arctic University. He is one of the researchers behind the study.

Delivered insulin to where it’s needed

It was researchers at the University of Sydney and Sydney Local Health District who, in collaboration with UiT, discovered many years ago that it was possible to deliver medicines via nano-carriers to liver. The method has then been further developed in Australia and in Europe.

Many medicines can be taken orally, but until now people have had to inject insulin into the body. McCourt explains that the problem with insulin with a nano-carrier is that it breaks down in the stomach and thus does not get to where it is needed in the body. This has been a major challenge for developing a diabetes medicine that can be taken orally.

But now the researchers have solved this challenge.

“We have created a coating to protect the insulin from being broken down by stomach acid and digestive enzymes on its way through the digestive system, keeping it safe until it reaches its destination, namely the liver,” says McCourt, who is a liver biologist.

The coating is then broken down in the liver by enzymes that are active only when the blood sugar levels are high, releasing the insulin where it can then act in the liver, muscle, and fat to remove sugar from the blood.

“This means that when blood sugar is high, there is a rapid release of insulin, and even more importantly, when blood sugar is low, no insulin is released,” says Nicholas J. Hunt at the University of Sydney who, together with Victoria Cogger, leads the project.

He explains that this is a more practical and patient-friendly method of managing diabetes because it greatly reduces the risk of a low blood sugar event occurring, namely hypoglycaemia and allows for the controlled released of insulin depending on the patient’s needs, unlike injections where all the insulin is released in one shot.

Fewer side effects

The new method works similarly to how insulin works in healthy people. The pancreas produces insulin which first passes through the liver where a large portion of it is absorbed and maintains stable blood sugar levels. In the new insulin method, the nano-carrier releases insulin in the liver, where it can be taken up or enter the blood to circulate in the body.

When insulin is injected subcutaneously, far more of it goes to the muscles and to adipose tissues that would normally happen if it was released from the pancreas, which can lead to fat accumulation. It can also lead to hypoglycaemia.

With the new method, there will be fewer such side effects, and no need for injection – or refrigeration.

Tested on baboons

The oral insulin has been tested on nematodes, on mice and rats. And lastly, the medicine has now been tested on baboons in the National Baboon Colony in Australia.

“In order to make the oral insulin palatable we incorporated it into sugar-free chocolate, this approach was well received” says Hunt.

He says that 20 baboons have taken part in this study. When they received the medicine, their blood sugar was lowered.

The baboons were normal, healthy baboons, but the oral insulin have also been tested on mice and rats that actually have diabetes. The mice and rats did not have hypoglycaemic events, gain weight or fat accumulation in the liver overcoming current challenges with injectable and other oral insulins.

What remains now is to test the new method on humans.

Ready for use in 2-3 years

“Trials on humans will start in 2025 led by the spin out company Endo Axiom Pty Ltd. Clinical trials are performed in 3 phases; in the phase I trial we will investigate the safety of the oral insulin and critically look at the incidence of hypoglycaemia in healthy and type 1 diabetic patients. Our team is very excited to see if we can reproduce the absent hypoglycaemia results seen in baboons in humans as this would be a huge step forward. The experiments follow strict quality requirements and must be carried out in collaboration with physicians to ensure that they are safe for the test subjects” says Hunt.

Source: UiT The Arctic University of Norway