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






Oral Estrogen Therapy for Menopause May Increase High Blood Pressure Risk

Women who take estrogen hormone pills to relieve menopausal symptoms may be more likely to develop high blood pressure than women using other forms of the medication, according to new research.

Hormone therapy may be prescribed to relieve symptoms of menopause, such as hot flashes, night sweats, mood changes and sleep disturbances. It’s also used in gender-affirming care and in contraception.

Menopause causes a woman’s body to produce less of the hormones estrogen and progesterone – which may increase cardiovascular risk factors, according to a 2020 scientific statement from the American Heart Association.

The study, published Monday in the journal Hypertension, explored factors associated with hormone therapy, including the types of estrogen used and how it was administered, whether orally or through topical and vaginal forms.

“We know estrogens ingested orally are metabolized through the liver, and this is associated with an increase in factors that can lead to higher blood pressure,” Cindy Kalenga, the study’s lead author, said in a news release. She is a medical student and doctoral candidate at the University of Calgary in Alberta, Canada.

Researchers used health data from more than 112,000 women in Canada ages 45 and older who filled at least two consecutive prescriptions – a six-month cycle – for estrogen-only therapy between 2008 and 2019. The women mostly used estradiol, a synthetic form of estrogen that most closely mimics what women’s bodies naturally produce pre-menopause, and conjugated equine estrogen, an animal-derived form of estrogen.

The results showed that women who used the therapy in pill form had a 14% higher risk of developing high blood pressure compared to those using estrogen topically, and a 19% greater risk compared to those using vaginal creams or suppositories.

Compared to estradiol, the use of conjugated equine estrogen was linked to an 8% higher risk of developing high blood pressure.

The study also associated the use of a higher estrogen dose for a longer time with a greater risk of high blood pressure. The findings suggest that some types of estrogen may have lower cardiovascular risks, Kalenga said.

“These may include low-dose, non-oral estrogen like estradiol in transdermal or vaginal forms – for the shortest possible time period,” Kalenga said. “These may also be associated with the lowest risk of hypertension. Of course, this must be balanced with the important benefits of hormone therapy, which include treatment of common menopausal symptoms.”

Research has found that starting menopausal hormone therapy in the early stages of menopause may have cardiovascular benefits – though not in the late stages, according to the 2020 AHA scientific statement.

Dr. Sofia B. Ahmed, a study co-author and a professor of medicine at the University of Calgary, said more than a quarter of the world’s female population is now older than 50, the average age at which natural menopause occurs for women. The number of women experiencing menopause is projected to reach 1 billion by 2025, she said.

“Approximately 80% of people going through menopause have symptoms, and for some it lasts up to seven years,” Ahmed said in the news release. “While menopause is a normal part of the aging process, it has huge implications for quality of life, economic impact, work productivity and social relationships. We need to give people the information they need to choose the most effective and safe hormonal treatments for menopause.”

Since the effects of different forms of hormone therapy on high blood pressure were based only on health records, the researchers cautioned of limitations in their findings. The study focused only on women taking estrogen-only therapy and did not include women younger than 45 or collect data about hysterectomies. The researchers also did not have data on menopausal status, so they instead relied on women’s use of estrogen therapy to indicate postmenopausal status.

Although the study focused on women in Canada, researchers noted that the country’s guidelines align with those from the American College of Obstetricians and Gynecologists in the United States. Both recommend appropriate use of hormone therapy and advise that it should not be considered for prevention or treatment of hypertension or heart disease.

The study’s authors said their future research will look at combined estrogen and progestin, as well as progestin-only formulations of hormone therapy and the impact on heart and kidney diseases.

“It’s really important to have greater knowledge on safe and effective hormonal treatments for women during menopause,” Ahmed said. “At the end of the day, it’s an individualized decision about what is best for the person going through menopause and should include open dialogue with their physician or health care team.”

Source: American Heart Association





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.





Worried About Cataracts? Here’s What You Need to Know

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

Cataracts are the leading cause of blindness around the world, but surgery can restore vision.

“Unlike many of the other major eye diseases, such as glaucoma or diabetes-related eye disease, cataracts can be easily and painlessly treated by surgery to remove and replace the eye’s lens, restoring sight for most patients,” said Jeff Todd, president and CEO of the nonprofit organization Prevent Blindness.

“We urge patients to work with their eye doctor to understand their diagnosis and the best available treatment options,” Todd said in a news release from the organization.

Here what else you should know about the common condition:

More than half of all Americans will have a cataract, a clouding of the eye’s lens that blocks or changes the passage of light into the eye, by the time they reach age 80, according to the organization.

Some patients have no early symptoms. The U.S. National Eye Institute says that people developing cataracts may notice cloudy or blurry vision, colors that look faded and difficulty seeing at night.

They may also see a halo around lights, have frequent changes to their eyeglass prescription or find that lamps, sunlight or headlights appear too bright.

Some may also see double, an issue that can go away as the cataract becomes larger.

About 4 million cataract surgeries take place each year in the United States, according to the American Academy of Ophthalmology.

In a cataract surgery, the eye surgeon may remove the lens with the cataract and replace it with an intraocular lens (IOL). The eye surgeon implants the new lens in about the same place as the natural lens, according to Prevent Blindness. This results in the most natural vision.

Different types of lenses are available:

  • A monofocal IOL, which is most commonly used, corrects for distance vision. Patients will likely still use glasses for close vision.
  • Another option is a multifocal IOL, which provides both distance and near correction at the same time.
  • An accommodative IOL can move or change shape inside the eye, allowing correct vision at different distances.
  • A toric IOL corrects vision for people who have astigmatism.

Source: HealthDay

Read more at Prevent Blindness

Guide to Cataract Surgery . . . . .





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