Scientists Get Closer to a Better PSA Test

Dennis Thompson wrote . . . . . . . . .

The most common screening test for prostate cancer so often returns a false positive result that it’s no longer recommended for men older than 70, and it’s offered as a personal choice for younger men.

But researchers think they’ve found a way to make the blood test for prostate-specific antigen (PSA) accurate enough to significantly reduce overdiagnosis and better predict dangerous cancers.

By calibrating PSA levels to each man’s genetics, doctors could control for other factors that might cause levels to be elevated, according to researchers at Stanford Medicine, in California.

The researchers envisioned combining the regular blood-based PSA test with an additional genetic analysis that detects inherited genetic variants that can affect PSA levels.

Elevated PSA levels can be a sign of prostate cancer, but levels can also be high due to other issues like inflammation, infection, an enlarged prostate or just old age, the study authors said in background notes.

“Some men have higher PSA levels due to their genetics,” senior researcher John Witte, a Stanford professor of epidemiology and population health, said in a university news release. “They don’t have cancer, but the higher PSA level leads to a cascade of unnecessary medical interventions like biopsy.”

By one estimate, less than one-third of men with elevated PSA levels were confirmed by a biopsy to have prostate cancer, the researchers reported. Moreover, 15% of men with normal PSA levels were later found to have prostate cancer.

But health experts are reluctant to write off the PSA test completely, given that prostate cancer rates are on the rise in the United States.

Prostate cancer rates rose by 3% a year between 2014 and 2019 after two decades of decline, and advanced prostate cancers increased by about 5% a year, the latest American Cancer Society statistics show.

The problem is that the signal delivered by current PSA screening — a man’s risk of prostate cancer — is too often mixed with background noise, the researchers explained.

“To improve the signal, which is the variation in PSA levels caused by a prostate tumor, we subtract out the noise, which in this case comes from genetics,” said lead researcher Linda Kachuri, an assistant professor of epidemiology and population health at Stanford.

For this study, the investigators looked at the genomes and PSA levels of nearly 96,000 men without prostate cancer to better understand the genetics behind normal variation in PSA levels. The data had been collected as part of earlier studies and included mostly men of European ancestry.

Through this analysis, the researchers estimated that 30% to 40% of the variation found in each man’s PSA levels constitutes “noise,” determined by genetic factors unrelated to cancer.

“Specifically, what we’re trying to capture are the genetic determinants of normal PSA variation,” Kachuri explained.

“This is different from our usual research deciphering the genetic basis of cancer,” Witte said. “We want to remove the non-cancer-related part that’s making PSA a less specific biomarker.”

The researchers identified 128 specific sites in the genome that can affect a man’s PSA level, and then developed a means to account for these normal genetic variations when calculating what they called a PSA polygenic score.

“A polygenic score is a quantitative way of summarizing someone’s genetic predisposition for a trait in a single value,” Kachuri said.

The researchers then tested their PSA polygenic score against data from a separate group of nearly 32,000 men without prostate cancer.

They found that the score could predict close to 10% of variation in PSA levels. However, it was much more effective among men of European ancestry than among men of East Asian or African ancestry.

Next, the researchers applied their score to a mixed group of men with and without prostate cancer, as confirmed by biopsy. The results showed that their PSA test could have spared roughly 30% of those men a biopsy.

The adjusted PSA levels particularly improved detection of the more aggressive forms of prostate cancer, although the benefit was noticeable only in men of European ancestry, according to the report.

“What we’re really worried about are those aggressive cases, so the fact that we’re able to show that genetically adjusted PSA is more predictive of aggressive disease is really promising,” Kachuri said.

Unfortunately, the adjusted PSA levels also would have missed approximately 9% of positive biopsies, the findings showed.

The majority of these missed cases were slow-growing tumors, which are not as dangerous and may not even require treatment. However, the misclassifications point to room for improving the score, the study authors said.

The team next plans a larger study that will include more men from diverse populations, to better improve the accuracy of the test.

“Ideally, we want to come up with a single score that works well for everybody, across the spectrum of ancestry,” Kachuri said.

Even a small improvement in screening could save lives, given that one in nine men in the United States will be diagnosed with prostate cancer and one in 40 will die from it, the researchers said.

The new study was published in Nature Medicine.

Source: HealthDay






Tiny Video Capsule Shows Promise as an Alternative to Endoscopy

While ingestible video capsule endoscopes have been around for many years, the capsules have been limited by the fact that they could not be controlled by physicians. They moved passively, driven only by gravity and the natural movement of the body. Now, according to a first-of-its-kind research study at George Washington University, physicians can remotely drive a miniature video capsule to all regions of the stomach to visualize and photograph potential problem areas. The new technology uses an external magnet and hand-held video game style joysticks to move the capsule in three-dimensions in the stomach. This new technology comes closer to the capabilities of a traditional tube-based endoscopy.

“A traditional endoscopy is an invasive procedure for patients, not to mention it is costly due to the need for anesthesia and time off work,” Andrew Meltzer, a professor of Emergency Medicine at the GW School of Medicine & Health Sciences, said. “If larger studies can prove this method is sufficiently sensitive to detect high-risk lesions, magnetically controlled capsules could be used as a quick and easy way to screen for health problems in the upper GI tract such as ulcers or stomach cancer.”

More than 7 million traditional endoscopies of the stomach and upper part of the intestine are performed every year in the United States to help doctors investigate and treat stomach pain, nausea, bleeding and other symptoms of disease, including cancer. Despite the benefits of traditional endoscopies, studies suggest some patients have trouble accessing the procedure.

In fact, Meltzer got interested in the magnetically controlled capsule endoscopy after seeing patients in the emergency room with stomach pain or suspected upper GI bleeding who faced barriers to getting a traditional endoscopy as an outpatient.

“I would have patients who came to the ER with concerns for a bleeding ulcer and, even if they were clinically stable, I would have no way to evaluate them without admitting them to the hospital for an endoscopy. We could not do an endoscopy in the ER and many patients faced unacceptable barriers to getting an outpatient endoscopy, a crucial diagnostic tool to preventing life-threatening hemorrhage,” Meltzer said. “To help address this problem, I started looking for less invasive ways to visualize the upper gastrointestinal tract for patients with suspected internal bleeding.”

The study is the first to test magnetically controlled capsule endoscopy in the United States. For patients who come to the ER or a doctor’s office with severe stomach pain, the ability to swallow a capsule and get a diagnosis on the spot – without a second appointment for a traditional endoscopy – is a real plus, not to mention potentially life-saving, says Meltzer. An external magnet allows the capsule to be painlessly driven to visualize all anatomic areas of the stomach and record video and photograph any possible bleeding, inflammatory or malignant lesions.

While using the joystick requires additional time and training, software is being developed that will use artificial intelligence to self-drive the capsule to all parts of the stomach with a push of the button and record any potential risky abnormalities. That would make it easier to use the system as a diagnostic tool or screening test. In addition, the videos can be easily transmitted for off-site review if a gastroenterologist is not on-site to over-read the images.

Meltzer and colleagues conducted a study of 40 patients at a physician office building using the magnetically controlled capsule endoscopy. They found that the doctor could direct the capsule to all major parts of the stomach with a 95 percent rate of visualization. Capsules were driven by the ER physician and then the study reports were reviewed by an attending gastroenterologist who was physically off-site.

To see how the new method compared with a traditional endoscopy, participants in the study also received a follow up endoscopy. No high-risk lesions were missed with the new method and 80 percent of the patients preferred the capsule method to the traditional endoscopy. The team found no safety problems associated with the new method.

Yet, Meltzer cautions that the study is a pilot and a much bigger trial with more patients must be conducted to make sure the method does not miss important lesions and can be used in place of an endoscopy. A major limitation of the capsule includes the inability to perform biopsies of lesions that are detected.

The study was published in iGIE, the open-access, online journal of the American Society for Gastrointestinal Endoscopy.

Source: George Washington University.





Why Do Some People Live to be a 100? Intestinal Bacteria May Hold the Answer

Some people live longer than others – possibly due to a unique combination of bacteria in their intestines, new research from the University of Copenhagen concludes.

“We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging related diseases,” says researcher behind new study. Photo: Unsplash.
We are pursuing the dream of eternal life. We fast to stay healthy. And each year, we spend billions of kroner on treatment to make sure we stay alive. But some people turn 100 years old all by themselves. Why is that?

Researchers from the Novo Nordisk Foundation Center for Protein Research at the University of Copenhagen have set out to find the answer.

Studying 176 healthy Japanese centenarians, the researchers learned that the combination of intestinal bacteria and bacterial viruses of these people is quite unique.

“We are always eager to find out why some people live extremely long lives. Previous research has shown that the intestinal bacteria of old Japanese citizens produce brand new molecules that make them resistant to pathogenic – that is, disease-promoting – microorganisms. And if their intestines are better protected against infection, well, then that is probably one of the things that cause them to live longer than others,” says Postdoc Joachim Johansen, who is first author of the new study.

Among other things, the new study shows that specific viruses in the intestines can have a beneficial effect on the intestinal flora and thus on our health.

“Our intestines contain billions of viruses living of and inside bacteria, and they could not care less about human cells; instead, they infect the bacterial cells. And seeing as there are hundreds of different types of bacteria in our intestines, there are also lots of bacterial viruses,” says Associate Professor Simon Rasmussen, last author of the new study.

Joachim Johansen adds that aside from the important, new, protective bacterial viruses, the researchers also found that the intestinal flora of the Japanese centenarians is extremely interesting.

“We found great biological diversity in both bacteria and bacterial viruses in the centenarians. High microbial diversity is usually associated with a healthy gut microbiome. And we expect people with a healthy gut microbiome to be better protected against aging related diseases,” says Joachim Johansen.

Once we know what the intestinal flora of centenarians looks like, we can get closer to understanding how we can increase the life expectancy of other people. Using an algorithm designed by the researchers, they managed to map the intestinal bacteria and bacterial viruses of the centenarians.

“We want to understand the dynamics of the intestinal flora. How do the different kinds of bacteria and viruses interact? How can we engineer a microbiome that can help us live healthy, long lives? Are some bacteria better than others? Using the algorithm, we are able to describe the balance between viruses and bacteria,” says Simon Rasmussen.

And if the researchers are able to understand the connection between viruses and bacteria in the Japanese centenarians, they may be able to tell what the optimal balance of viruses and bacteria looks like.

Optimising intestinal bacteria

More specifically, the new knowledge on intestinal bacteria may help us understand how we should optimise the bacteria found in the human body to protect it against disease.

“We have learned that if a virus pays a bacterium a visit, it may actually strengthen the bacterium. The viruses we found in the healthy Japanese centenarians contained extra genes that could boost the bacteria. We learned that they were able to boost the transformation of specific molecules in the intestines, which might serve to stabilise the intestinal flora and counteract inflammation,” says Joachim Johansen, and Simon Rasmussen adds:

“If you discover bacteria and viruses that have a positive effect on the human intestinal flora, the obvious next step is to find out whether only some or all of us have them. If we are able to get these bacteria and their viruses to move in with the people who do not have them, more people could benefit from them.”

Even though this requires more research, the new insight is significant, because we are able to modify the intestinal flora.

“Intestinal bacteria are a natural part of the human body and of our natural environment. And the crazy thing is that we can actually change the composition of intestinal bacteria. We cannot change the genes – at least not for a long time to come. If we know why viruses and intestinal bacteria are a good match, it will be a lot easier for us to change something that actually affects our health,” says Simon Rasmussen.

The study, “Centenarians have a diverse gut virome with the potential to modulate metabolism and promote healthy lifespan”, has been published in Nature Microbiology.

Source: University of Copenhagen





Low-Dose Colchicine Might Prevent or Delay Knee, Hip Replacements

Amy Norton wrote . . . . . . . . .

An anti-inflammatory drug that has been around for over 2,000 years might help delay a very modern problem: hip and knee replacements.

That’s the suggestion of a new study finding that older adults who used the drug — called colchicine — were less likely to need hip or knee replacement surgery over the next two years, versus those given placebo pills.

The study, published in the Annals of Internal Medicine, does come with a big caveat, researchers noted: The patients were part of a trial testing colchicine for warding off heart trouble — not joint replacements.

So the findings do not prove the medication actually stalled the progression of knee or hip osteoarthritis. That’s the common, age-related form of arthritis where the cartilage cushioning the joints gradually breaks down.

But the results do make a “strong argument” for studying colchicine as a treatment for osteoarthritis, said lead researcher Michelle Heijman, of Sint Maartens Clinic, in Nijmegen, the Netherlands.

Until then, she said, the drug cannot be recommended as a treatment for the joint disease.

As it stands, medications for osteoarthritis offer pain relief, but there are none that can slow the underlying joint destruction.

Colchicine is an oral drug that has long been prescribed for a different form of arthritis called gout. Doctors also sometimes use it to treat pericarditis, where the sac around the heart becomes inflamed.

More recently, in 2020, a clinical trial found that colchicine benefits people who’d recently suffered a heart attack: It reduced their risk of further heart complications and stroke over the next two years, in comparison to a placebo.

Colchicine works by inhibiting the body’s production of particular inflammatory proteins — ones that have been implicated in osteoarthritis progression. So Heijman’s team reasoned that patients given colchicine in the 2020 trial might also have had a lower likelihood of hip or knee replacement surgery.

To find out, they took a second look at the trial data.

The study involved over 5,500 patients who were 66, on average. Half were randomly assigned to take a low dose of colchicine (0.5 milligrams per day), while the other half received a placebo.

Heijman’s team found that over two-plus years, 2.5% of colchicine patients underwent hip or knee replacement surgery, versus 3.5% of placebo patients.

A shortfall of the data is that there was no information on whether people had osteoarthritis. But, Heijman said, the vast majority of hip and knee replacements are done because of severe osteoarthritis. And the researchers think the findings do reflect an effect of colchicine on arthritis progression.

However, Heijman said, this trial focused on heart disease patients, so it cannot be used to change treatment guidelines for osteoarthritis.

“That’s why we want to conduct a follow-up study that is specifically aimed at osteoarthritis,” she said. “If we can confirm that colchicine works, we can finally offer osteoarthritis patients a safe and effective therapy.”

Dr. Linda Russell, a rheumatologist at the Hospital for Special Surgery, in New York City, agreed that colchicine should be further studied as an osteoarthritis treatment.

She noted that colchicine has a long history of use, and it is “relatively safe and well-tolerated.”

In fact, colchicine’s use dates back a couple of thousand years, when the ancient Greeks employed it as a laxative. Accordingly, its most common side effects are gastrointestinal, including abdominal pain, nausea and diarrhea.

Like Heijman, Russell said the new findings are not enough to prove that colchicine delays joint replacements. For one, it’s not clear how many patients already had surgery planned before they entered the trial.

For now, Russell said that people with osteoarthritis can do some things to prevent or delay a joint replacement: lose weight, if needed, and strengthen the muscles supporting the affected joint.

Those tactics, Russell said, may both slow the underlying disease progression and ease chronic pain — the key reason that people opt for surgery.

Source: HealthDay





Compounds in Chocolate, Berries Might Help Boost Memory As You Age

Cara Murez wrote . . . . . . . . .

You’ll likely lose some of your memory and thinking abilities as you age, but nutrients called flavanols might help thwart that decline, a new study suggests.

Not getting enough flavanols — natural compounds found in fruits, vegetables and even chocolate — could be driving that age-related memory loss, researchers say.

This research is the pinnacle of 15 years of work showing that flavanols seem to benefit the dentate gyrus, an area within the brain’s hippocampus that is critical to memory.

“This is the first time we can conclude that flavanols are acting as a nutrient for the aging brain,” said Dr. Scott Small, a professor of neurology and director of the Alzheimer’s Disease Research Center at Columbia University College of Physicians and Surgeons. “We show in this study, because we had biomarkers of flavanols, that if you’re relatively deficient in your flavanols, that seems to be driving your age-related memory decline.”

This study was funded by the U.S. National Institutes of Health and Mars Edge, a subsidiary of the candy company.

It’s possible that just as babies need certain nutrients for their developing brains, the aging brain also requires specific nutrients for optimal health, Small said.

Now that people live longer, scientists are looking into a series of recommendations of nutrients that are beneficial for the aging body and brain, he noted.

“I’d like to believe that this is one of the first studies that is beginning to establish that dietary recommendation,” Small said.

Besides berries and dark chocolate, other flavanol-containing foods include apples — particularly the peels — grapes, citrus fruits, cocoa and green tea. Good vegetable sources of flavanols are onions, hot peppers, kale, broccoli, rutabagas and spinach, according to the U.S. Department of Agriculture.

“I believe that you could consume enough flavanols to prevent yourself from being deficient,” Small said.

However, he urged people not to focus on getting this nutrient through chocolate. “There’s no way you can eat enough chocolate to have this benefit. In fact, if you tried, you would die first,” Small said.

Prior research in mice found that a particular substance in flavanols called epicatechin enhanced the growth of neurons and blood vessels, improving memory.

In humans, a small study linked the dentate gyrus to cognitive, or mental, aging. A larger trial found that flavanols improved memory, having the greatest impact on people who had a poor-quality diet to start.

To study this further, researchers randomly assigned 3,500 healthy older adults to receive either a placebo or a daily flavanol supplement in pill form. The supplements contained 500 mg of flavanols, including 80 mg of epicatechins (an amount that’s recommended you get from food).

Participants answered questions about their diet, and then did web-based activities to assess short-term memory that involved the hippocampus, repeating them after years one, two and three.

More than one-third of participants also supplied urine samples, so that researchers could measure a biomarker for dietary flavanol levels.

No one was severely flavanol-deficient, although those with mild deficiency benefited from flavanol supplements, researchers said.

Researchers also found that memory scores improved just slightly for the entire group taking the supplements, possibly because most already had flavanol-rich diets.

Yet those who reported having a poor diet and who had lower baseline levels of flavanols had memory scores improve by an average of about 11% compared to those on the placebo at the end of the first year. Their memory improved 16% from baseline.

They sustained the one-year improvement for at least two more years.

However, flavanols only improved memory governed by the hippocampus and not other areas of the brain, the researchers noted.

Emma Laing is director of dietetics at the University of Georgia and a national spokesperson for the Academy of Nutrition and Dietetics. She said flavanols are one of several sub-classifications of flavonoids, naturally occurring bioactive compounds linked to human health.

“Consuming foods high in flavanols has been shown in research studies to benefit health and reduce the risk for chronic diseases involving the brain, heart and other organs,” said Laing, who was not involved in this study.

These nutrients give foods like peaches and apples their bright colors, Laing said.

She noted that the role of flavanols on neurological health is an exciting, ongoing area of research with a lot left to learn.

“Intentionally adding flavanol-rich foods to your eating pattern is a relatively simple lifestyle change that you could make to support your health. Many foods naturally contain these compounds, so aiming to add one or more servings of flavanol-rich foods per week would be a realistic place to start,” Laing said.

Lang also recommended eating nutrient-dense foods, getting enough sleep, exercising, staying well-hydrated and avoiding alcohol as ways to reduce the risk of chronic disease and improve overall health.

Because of the study’s design, Small said it can’t definitively conclude that low dietary intake of flavanols alone causes poor memory, only that there’s an association.

The study was published in the journal Proceedings of the National Academy of Sciences.

Source: HealthDay